SEARCH · Search PubMed

Results for “RELAXATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources

PubMed2000

Apamin-sensitive, non-nitric oxide (NO) endothelium-dependent relaxations to bradykinin in the bovine isolated coronary artery: no role for cytochrome P450 and K+.

Since cytochrome P(450)-derived metabolites of arachidonic acid and K(+) have been implicated in endothelium-derived hyperpolarizing factor (EDHF)-dependent responses, the aim of this study was to determine whether such factors contribute to non-nitric oxide (NO), endothelium-dependent relaxation to bradykinin (BK) in bovine isolated coronary artery. In rings of artery contracted with U46619 and treated with indomethacin (3 microM) and N(G)-nitro-L-arginine (L-NOARG; 100 microM), relaxation to BK (0.01 nM-0.3 microM) was blocked by approximately 60% after inhibition of K(+) channels with either high extracellular K(+) (high [K(+)](o); 15 - 67 mM) or apamin (0.3 microM). Ouabain (1 microM), an inhibitor of Na(+)/K(+)-ATPase, decreased the sensitivity to BK without affecting the maximum response. In L-NOARG-treated rings, ouabain had no further effect on the relaxation to BK. An inhibitor of inward-rectifying K(+) channels, Ba(2+) (30 microM), had no effect on relaxations to BK in the absence or presence of either L-NOARG or ouabain. KCl (2.5 - 10 mM) elicited small relaxations ( approximately 20%) that were abolished by nifedipine (0.3 microM) and ouabain. Both the high [K(+)](o)/apamin-sensitive relaxation to BK, and the relaxation to the K(ATP) channel-opener, levcromakalim (0.6 microM), were unaffected by the cytochrome P(450) inhibitor, 7-ethoxyresorufin (10 microM), or by co-treatment with a phospholipase A(2) inhibitor, arachidonyl trifluoromethyl ketone (AACOCF(3); 3 microM) and a diacylglycerol (DAG)-lipase inhibitor, 1, 6-bis-(cyclohexyloximinocarbonylamino)-hexane (RHC 80267; 30 microM). The non-NO/high [K(+)](o)-insensitive, approximately 40% relaxation to BK was, however, abolished by these treatments. Therefore, neither cytochrome P(450)-derived metabolites of arachidonic acid nor K(+) appear to mediate the EDHF-like relaxation to BK (i.e the non-NO, high [K(+)](o)/apamin-sensitive component) in bovine coronary arteries. Cytochrome P(450)-derived metabolites may be released at higher BK concentrations to act in parallel with NO and the high [K(+)](o)/apamin-sensitive mechanism.

Animals↗

PubMed2000

Influence of bilirubin and other antioxidants on nitrergic relaxation in the pig gastric fundus.

1. The influence of several antioxidants (bilirubin, urate, ascorbate, alpha-tocopherol, glutathione (GSH), Cu/Zn superoxide dismutase (SOD) and the manganese SOD mimic EUK-8) on nitrergic relaxations induced by either exogenous nitric oxide (NO; 10(-5) M) or electrical field stimulation (4 Hz; 10 s and 3 min) was studied in the pig gastric fundus. 2. Ascorbate (5x10(-4) M), alpha-tocopherol (4x10(-4) M), SOD (300 - 1000 u ml(-1)) and EUK-8 (3x10(-4) M) did not influence the relaxations to exogenous NO. In the presence of GSH (5x10(-4) M), the short-lasting relaxation to NO became biphasic, potentiated and prolonged. Urate (4x10(-4) M) and bilirubin (2x10(-4) M) also potentiated the relaxant effect of NO. None of the antioxidants influenced the electrically evoked relaxations. 3. 6-Anilino-5,8-quinolinedione (LY83583; 10(-5) M) had no influence on nitrergic nerve stimulation but nearly abolished the relaxant response to exogenous NO. Urate and GSH completely prevented this inhibitory effect, while it was partially reversed by SOD and bilirubin. Ascorbate, alpha-tocopherol and EUK-8 were without effect. 4. Hydroquinone (10(-4) M) did not affect the electrically induced nitrergic relaxations, but markedly reduced NO-induced relaxations. The inhibition of exogenous NO by hydroquinone was completely prevented by urate and GSH. SOD and ascorbate afforded partial protection, while bilirubin, EUK-8 and alpha-tocopherol were ineffective. 5. Hydroxocobalamin (10(-4) M) inhibited relaxations to NO by 50%, but not the electrically induced responses. Full protection versus this inhibitory effect was obtained with urate, GSH and alpha-tocopherol. 6. These results strengthen the hypothesis that several endogenous antioxidant defense mechanisms, enzymatic as well as non-enzymatic, might play a role in the nitrergic neurotransmission process.

Aminoquinolines↗

PubMed2003

Evidence against beta 3-adrenoceptors or low affinity state of beta 1-adrenoceptors mediating relaxation in rat isolated aorta.

1 The presence of beta(3)-adrenoceptors and the low affinity state of the beta(1)-adrenoceptor (formerly "putative beta(4)-adrenoceptor") was investigated in ring preparations of rat isolated aorta preconstricted with phenylephrine or prostaglandin F(2alpha) (PGF(2alpha)). Relaxant responses to isoprenaline, selective beta(3)-adrenoceptor agonists (BRL 37344, SR 58611A, CL 316243) and non-conventional partial agonists (CGP 12177A, cyanopindolol, pindolol) were obtained. 2 In phenylephrine-constricted, but not PGF(2alpha)-constricted rings, relaxations to isoprenaline showed a propranolol-resistant component. 3 In phenylephrine-constricted rings, relaxations to BRL 37344 (pEC(50), 4.64) and SR 58611A (pEC(50), 4.94) were not antagonized by the selective beta(3)-adrenoceptor antagonist SR 59230A (< or =1 microM). CL 316243 (< or =100 microM) failed to produce relaxation. In PGF(2alpha)-constricted rings only SR 58611A produced relaxation, which was not affected by SR 59230A (< or =3 microM). 4 Non-conventional partial agonists produced relaxation in phenylephrine-constricted but not PGF(2alpha)-constricted rings. The relaxation to CGP 12177A was unaffected by SR 59230A (< or =1 microM) or by CGP 20712A (10 microM), reported to block the low affinity state of the beta(1)-adrenoceptor. 5 beta-adrenoceptor antagonists also produced relaxation in phenylephrine-constricted rings with an order of potency of (pEC(50) values): bupranolol (5.5) approximately 38;SR 59230A (5.47) approximately 38;cyanopindolol (5.47)>pindolol (5.30)>alprenolol (5.10)>propranolol (4.83)>ICI 118551 (4.60)>CGP 12177A (4.38) approximately 38;CGP 20712A (4.35). Bupranolol (100 microM), alprenolol (30 microM), propranolol (100 microM) and SR 59230A (10 microM) produced no relaxation in PGF(2alpha)-constricted rings. 6 These results provide no evidence for the presence of functional beta(3)-adrenoceptors or the low affinity state of the beta(1)-adrenoceptor in rat aorta.

Adrenergic beta-1 Receptor Agonists↗

PubMed2003

In vivo characterization of 5-HT1A receptor-mediated gastric relaxation in conscious dogs.

Accumulating data have been published emphasizing the important role of 5-hydroxytryptamine (5-HT) receptors in proximal stomach relaxation. However, a proper in vivo characterization of 5-HT receptors mediating gastric relaxation is still missing. In the current study, we focus on the in vivo characterization of 5-HT1A receptors mediating relaxation of the proximal stomach in conscious dogs. Beagle dogs were equipped with a gastric fistula. In the conscious state, volume changes within an intragastric bag were measured at constant pressure by means of a barostat. Results are presented as the maximum volume increase after treatment (mean+/-s.e.m.). All drugs were injected intravenously. The 5-HT1A receptor agonist flesinoxan (10, 50, 100 and 150 microg kg-1) induced a dose-dependent relaxation of the canine proximal stomach (50+/-10, 230+/-51, 290+/-38 and 275+/-33 ml, respectively; n=9-11). The selective 5-HT1A receptor antagonist WAY-100635 dose-dependently inhibited the flesinoxan-induced relaxation. NG-nitro-l-arginine methyl ester did not affect this relaxation, suggesting that nitrergic nerves are not involved. After supradiaphragmatic vagotomy, the baseline of the intragastric volume was larger compared to that before vagotomy (317+/-50 vs 142+/-28 ml, respectively; n=5). Compensation for this by either reduction of the intraballoon pressure or infusion of a contractile dose of bethanechol did not establish a condition in which flesinoxan was able to relax the stomach. In contrast, nitroprusside induced a significant gastric relaxation when tone was increased by bethanechol. It is concluded that flesinoxan induces proximal gastric relaxation in conscious dogs via 5-HT1A receptors. The response is mediated through a vagal pathway without involvement of nitrergic nerves.

Animals↗

PubMed1997

Endothelium-dependent vascular smooth muscle relaxation activated by electrical field stimulation.

Electrical field stimulation (EFS) produced relaxation of contracted arteries in the presence of tetrodotoxin. In the present study the contributions of vascular smooth muscle repolarization and endothelial release of nitric oxide to the relaxation response were investigated using isolated rat tail arteries and bovine aortic endothelial cells (BAEC). Intact and endothelium-denuded rings or intact, pressurized artery segments were contracted with either phenylephrine or KCl prior to EFS. Electrical field stimulation induced a small relaxation in denuded, phenylephrine contracted rings that was inhibited by the K+ channel blockers glibenclamide and BaCl2. In intact, phenylephrine-contracted rings, EFS induced significantly larger relaxations that were inhibited by BaCl2 as well as by L-NAME, an inhibitor of nitric oxide (NO) synthase, and methylene blue. EFS-induced relaxations were completely inhibited when BaCl2 and L-NAME or methylene blue were combined. Exposure to Ca(2+)-free buffer or diltiazem also inhibited the relaxation while ascorbic acid had no effect. Effluent from electrically stimulated BAEC caused denuded, phenylephrine contracted rings to relax. The ability of the effluent to cause relaxation was almost completely blocked by exposure of the BAEC to L-NAME or exposure of the recipient vascular smooth muscle to methylene blue; glibenclamide caused partial blockade. Simultaneous measurements of membrane potential and intraluminal pressure showed that EFS-induced membrane repolarization preceded changes in steady-state pressure. It is concluded that (1) the smooth muscle cells possess an endothelium-independent repolarization mechanism, (2) EFS causes endothelial cells of intact arteries to release NO and possibly a hyperpolarizing factor, (3) EFS of BAEC causes release of NO, and (4) EFS-induced relaxation depends on vascular smooth muscle cell membrane repolarization and endothelial cell release of vasoactive substances.

Animals↗

PubMed2000

The effects of isolated lipoproteins and triglyceride, combined oxidized low density lipoprotein (LDL) plus triglyceride, and combined oxidized LDL plus high density lipoprotein on the contractile and relaxation response of rabbit cavernous smooth muscle.

The aim of this study was to investigate the effects of isolated lipoproteins and triglyceride (TG), and the effects of combined oxidized low density lipoprotein (LDL) plus TG and the combined oxidized LDL plus high density lipoprotein (HDL) on the contractility and relaxation response of rabbit cavernous smooth muscle. Cavernous muscle strips from New Zealand White rabbits were studied in organ chambers for isometric tension measurement. The strips were exposed to HDL, LDL, oxidized LDL, TG, combined oxidized LDL plus TG and combined oxidized LDL plus HDL for 30 min. Both HDL and LDL did not affect contraction and relaxation responses of the cavernous muscles. The oxidized LDL did not affect norepinephrine (NE)-induced contractility of the strips, but significantly (p < 0.05) decreased the relaxation response to endothelium-dependent agonist, acetylcholine (Ach). Non-specific NO synthase inhibitor (L-NAME) completely inhibited the relaxation response to Ach, and L-arginine partially improved the diminished relaxation. TG did not significantly change the relaxation responses to Ach, but decreased the contractility of cavernous muscle to NE. Neither the combined oxidized LDL plus TG nor oxidized LDL plus HDL had significant synergistic or detoxication effects on the contractility and relaxation responses. In conclusion, oxidized LDL may have acute toxic effects on the endothelium-dependent, NO-mediated relaxation, but not on the contractility, of rabbit cavernous smooth muscle. TG may decrease contractility of the cavernous muscle. There may be neither synergistic nor detoxication effects on the contractility and relaxation response when TG or HDL is added to the oxidized LDL.

Animals↗

PubMed1999

Beta1- and beta3-adrenoceptors mediate relaxation in ovine trachealis smooth muscle.

Isoprenaline (non-selective) and noradrenaline (beta1-selective) concentration-dependently relaxed ovine tracheal strips precontracted with carbachol. The pD2 values were 7.07 +/- 0.08 and 6.13 +/- 0.10 for isoprenaline and noradrenaline, respectively. In the same preparation, salbutamol either produced weak relaxation or in some cases, contractile responses indicating the presence of very little or no beta2-adrenoceptors in this preparation. Isoprenaline-and noradrenaline-induced relaxations were antagonized by propranolol and atenolol with pA2 values in the range reported in the literature for an action on beta1-adrenoceptors. ICI 118551 also antagonized isoprenaline- and noradrenaline-induced relaxation but at concentrations much higher than are required to block beta2-adrenoceptors, confirming that beta2-adrenoceptors do not contribute significantly to these responses. The selective beta3-adrenoceptor agonist, BRL 37344A produced concentration-dependent relaxation of tracheal strips. BRL 37344A was a full agonist producing 100% relaxation of carbachol-induced tone. BRL 37344A-induced relaxation was weakly antagonized by propranolol confirming an action, mainly, on beta3-adrenoceptors. Cyanopindolol antagonized isoprenaline-induced relaxation (in the presence of propranolol, 10(-7) M) with a pA2 value of 8.06 +/- 0.24. It was therefore concluded that beta1- and beta3-adrenoceptors mediated agonist-induced relaxation in sheep tracheal strips.

Adrenergic beta-Agonists↗

PubMed2002

Hydrogen-potassium ATPase inhibitors induce relaxation on rabbit prostatic strips in vitro.

BACKGROUND: To determine the relaxant effect of omeprazole and lansaprazole, hydrogen-potassium (H+-K+) ATPase inhibitors, on rabbit prostatic tissue in vitro. METHODS: Male New Zealand white rabbits were sacrificed and their prostatic tissues were removed. The prostatic stromal strips were mounted in organ baths and relaxation responses were obtained in precontracted tissues with phenylephrine, carbachol and potassium chloride (KCl). Relaxation responses were controlled in the presence of various antagonists to explain the mechanism for relaxation exerted by omeprazole and lansaprazole. RESULTS: Omeprazole and lansaprazole caused similar relaxation responses in the prostatic strips precontracted with phenylephrine, carbachol and KCl. The addition of prostaglandin synthase inhibitor indomethacin, nitric oxide synthase inhibitor L-NAME, potassium channel blockers, glibenclamide and tetraethylammonium into the organ baths did not change the relaxations induced by omeprazole and lansaprazole in vitro. CONCLUSION: Omeprazole and lansaprazole cause a relaxation in prostatic stromal tissue precontracted with phenyephrine, carbachol and KC1 in vitro. This relaxant effect is independent of H+-K+ ATPase inhibition. Additionally, cyclooxygenase and nitric oxide pathways do not contribute to this relaxant effect. Further studies are required to determine whether these drugs may have a beneficial effect in the non-operative treatment of benign prostatic hyperplasia.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2003

Comparison of the relaxant effects of alfuzosin, phentolamine and sildenafil on rabbit isolated corpus cavernosum.

OBJECTIVE: To compare the direct relaxant effects of alfuzosin, phentolamine and sildenafil in rabbit isolated corpus cavernosum (CC) pre-contracted with phenylephrine or KCl. MATERIALS AND METHODS: Penile erectile tissue was obtained from male New Zealand White rabbits (22-26 weeks old). The CC was cut into longitudinal strips and mounted under 2 g resting tension in 5-mL jacketed organ baths containing a modified Krebs solution bubbled with 95% O2, 5% CO2 and maintained at 37 degrees C. Tissue strips were pre-contracted by 60 mmol/L KCl or 10 micro mol/L phenylephrine. After obtaining a stable plateau of contractions, test compounds were added to the organ bath. The relaxant potencies were expressed as the percentage of inhibition of the plateau of contraction induced by 10 micro mol/L phenylephrine. RESULTS: Alfuzosin showed a concentration-dependent relaxing effect on rabbit CC pre-contracted by 10 micro mol/L phenylephrine, with a mean (sd) pIC50 of 7.64 (0.06). The relaxant effect was unaffected by pre-incubation with 100 micro mol/L Nomega-nitro-l-arginine methyl ester (L-NAME). Phentolamine had a potency similar to alfuzosin, with a pIC50 of 7.44 (0.08). Both alfuzosin and phentolamine were completely ineffective on the plateau of contraction induced by 60 mmol/L KCl. In contrast to alfuzosin, sildenafil was equipotent in relaxing the rabbit CC against each contractile agent, with pIC50 values of 7.25 (0.09) and 7.23 (0.22) with 10 micro mol/L phenylephrine and 60 mmol/L KCl, respectively. The relaxant response to sildenafil was partly blocked by pretreatment with 100 micro mol/L L-NAME, with pIC50 values of 7.94 (0.09) and 6.63 (0.32) without and with L-NAME, respectively. Sildenafil, incubated for 45 min at 10 micro mol/L, had no relaxant effect on the resting tension of the preparation or on the concentration-response curve to phenylephrine. CONCLUSIONS: The direct relaxant effect of alfuzosin is mediated through alpha1-adrenoceptor blockade. The relaxations induced by phentolamine and alfuzosin are independent of nitric oxide, whereas those induced by sildenafil are, at least partly, sensitive to L-NAME and a selective soluble guanylate cyclase inhibitor, indicating the involvement of nitric oxide and soluble guanylate cyclase. Alfuzosin and phentolamine effectively counteract alpha1-adrenoceptor-mediated contractions of rabbit CC. If valid for human CC, such an effect may contribute to an improved erectile function in patients treated for benign prostatic hyperplasia.

Adrenergic alpha-Antagonists↗

PubMed2001

Effects of some divalent cations on nitrergic relaxations in the mouse corpus cavernosum.

Acute effects of some divalent cations (Cd2+, Ni2+, Co2+, Zn2+, Mn2+ and Sn2+) were investigated on neurogenic and endothelium-dependent relaxations in the isolated mouse corpus cavernosum. Neither neurogenic nor endothelium-dependent relaxation was affected by cations at the concentrations used (up to 100 microM), except Cd2+. Although Cd2+ (20 and 40 microM) did not cause any significant alteration in the acetylcholine- (ACh) or sodium nitroprusside- (SNP) induced relaxation, it inhibited electrical field stimulation- (EFS) produced relaxation significantly. Zn2+ and selenium could not reverse this inhibitory action. Cd2+ did block the EFS-evoked guanethidine-sensitive contraction in the presence of N(G)-nitro-L-arginine. Elevation of external Ca2+ content significantly reduced the inhibitions due to Cd2+ on the EFS-induced relaxation and on the EFS-evoked guanethidine-sensitive contraction. In the Ca2+-omitted medium, EFS-induced relaxation disappeared, while acetylcholine-elicited relaxation resisted. Verapamil was ineffective on the relaxation produced by EFS or acetylcholine. However, it significantly diminished phenylephrine-induced contractions. These findings suggest that unlike other cations at the concentrations used in the present study, Cd2+ may have an effect on an external Ca2+-dependent mechanism at the neuronal level, and this effect may be responsible for its acute inhibitory action on the neurogenic relaxation in the mouse corpus cavernosum.

Animals↗

PubMed1996

Prostaglandin E2 modulates neurally induced nonadrenergic, noncholinergic gastric relaxations in the rabbit in vivo.

BACKGROUND & AIMS: Prostaglandin (PG) E2 has been shown to modulate adrenergic and cholinergic neurotransmission in the gut. This study investigated PGE2 influence on vagally induced, nonadrenergic, noncholinergic (NANC) gastric relaxations. METHODS: Mechanical activity of the stomach was recorded in anesthetized rabbits. RESULTS: In atropine-treated animals, electrical vagal stimulation or arterial bolus injection of the ganglion stimulant dimethyl phenylpiperazinium iodide (DMPP) evoked inhibitory responses that varied from a brisk relaxation, interrupted by a poststimulus excitatory motility (biphasic response), to a long-lasting relaxation (monophasic response). PGE2 reduced and, at the highest doses, abolished the neurally induced relaxant responses elicited either by vagal stimulation or DMPP administration but did not affect the gastric relaxation caused by adenosine triphosphate (ATP), sodium nitroprusside (SNP), or vasoactive intestinal polypeptide (VIP). ATP or 2-methylthioadenosine triphosphate (2-MeSATP) reduced and then suppressed vagally induced inhibitory motility; the relaxant responses elicited by SNP, VIP, and ATP itself were not influenced. After administration of the prostaglandin synthesis inhibitor suprofen, ATP and 2-MeSATP failed to block vagally induced inhibitory responses. Arterial infusion of adenosine at the highest rates did not influence the amplitude of the vagally induced relaxant responses. Following theophylline administration, ATP still blocked the relaxation elicited by vagal stimulation. CONCLUSIONS: PGE2 may modulate NANC inhibitory neurotransmission in the stomach. The effects of ATP on the neurally induced NANC gastric relaxation may be caused by PGE2.

Adenosine↗

PubMed2001

Relaxation training as complementary therapy for mild hypertension control and the implications of evidence-based medicine.

Relaxation therapy for the treatment of hypertension presented a number of challenges, in terms of conducting and using research as well as gaining the wider acceptance of this complementary therapy in common practice in Hong Kong. Two issues were central to the current implementation of complementary therapies: the evidence-based practice movement and the management of risk during the implementation of new therapies. A major concern was how to maximize the chance of inclusion of research on complementary therapies in evidence-based practice systematic reviews. This was thought to be achievable by making the data amenable to meta-analysis when small samples may be unavoidable. The empirical work examined the effects of three relaxation therapies for the reduction of high blood pressure in nine Chinese subjects. Subjects were randomly assigned to three groups: (a) progressive muscle relaxation, (b) stretch release relaxation and (c) cognitive imagery relaxation. Systolic, diastolic blood pressure and heart rate were assessed in a baseline session, the 8th post-treatment session, and a 30-days follow-up session. Datawere analyzed using ANOVA and Paired sample t-test. One-Sample Kolmogorov-Smirnov Tests for the normal distribution were performed among the three groups. The results verified that the normality assumption for the data had not been violated. Results revealed that in the context of the study all relaxation therapies can reduce blood pressure in Chinese subjects, but stretch release relaxation and progressive muscle relaxation therapies appeared to be more effective in lowering blood pressure compared to cognitive imagery relaxation. These data are in a form available for meta-analysis at a later date. The study also shows a degree of clinical significance and validation with respect to a Hong Kong population. It demonstrates ways in which the inclusion of research on complementary therapies in systematic reviews can be maximized.

Adult↗

PubMed1992

Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission.

BACKGROUND: Nitric oxide has been identified as an endothelium-derived relaxing factor in blood vessels. We tried to determine whether it is involved in the relaxation of the corpus cavernosum that allows penile erection. The relaxation of this smooth muscle is known to occur in response to stimulation by nonadrenergic, noncholinergic neurons. METHODS: We studied strips of corpus cavernosum tissue obtained from 21 men in whom penile prostheses were inserted because of impotence. The mounted smooth-muscle specimens were pretreated with guanethidine and atropine and submaximally contracted with phenylephrine. We then studied the smooth-muscle relaxant responses to stimulation by an electrical field and to nitric oxide. RESULTS: Electrical-field stimulation caused a marked, transient, frequency-dependent relaxation of the corpus cavernosum that was inhibited in the presence of N-nitro-L-arginine and N-amino-L-arginine, which selectively inhibit the biosynthesis of nitric oxide from L-arginine. The addition of excess L-arginine, but not D-arginine, largely reversed these inhibitory effects. The specific liberation of nitric oxide (by S-nitroso-N-acetylpenicillamine) caused rapid, complete, and concentration-dependent relaxation of the corpus cavernosum. The relaxation caused by either electrical stimulation or nitric oxide was enhanced by a selective inhibitor of cyclic guanosine monophosphate (GMP) phosphodiesterase (M&B 22,948). Relaxation was inhibited by methylene blue, which inhibits cyclic GMP synthesis. CONCLUSIONS: Our findings support the hypothesis that nitric oxide is involved in the nonadrenergic, noncholinergic neurotransmission that leads to the smooth-muscle relaxation in the corpus cavernosum that permits penile erection. Defects in this pathway may cause some forms of impotence.

Adult↗

PubMed1996

Time course of changes in arterial relaxation following subarachnoid hemorrhage in dogs.

This experiment determined if the time course of inhibition of arterial relaxation correlates with angiographic vasospasm following subarachnoid hemorrhage (SAH) in dogs. Twenty-two dogs underwent cerebral angiography followed by SAH by 2 injections of blood into the cisterna magna. Dogs had repeated angiography and were sacrificed 4 (n = 5), 7 (n = 4), 10 (n = 4), 14 (n = 5), or 21 (n = 4) days later. Four dogs served as controls and underwent angiography only, followed by sacrifice. The basilar arteries were removed and studied under isometric tension to determine relaxations to acetylcholine and sodium nitroprusside. There was significant reduction in basilar artery diameter at each time after SAH (day 4: -52% +/- 10%, day 7: -37% +/- 10%, day 10: -54% +/- 10%, day 14: -37% +/- 10%, and day 21: -26% +/- 18%, p < 0.05, analysis of variance), although there were no pairwise differences in the degree of vasospasm over time. Relaxations to acetylcholine were significantly reduced at all times after SAH (p < 0.05, analysis of variance). Relaxations to sodium nitroprusside were significantly reduced 7 days after SAH. There was a significant linear correlation between increasing time after SAH and decreasing relaxation to acetylcholine. There was no correlation in univariate or multivariate analysis, between the time after SAH, the degree of vasospasm and the relaxation to acetylcholine or sodium nitroprusside. It is concluded that inhibition of arterial relaxation depends on the relaxant used and does not correlate with vasospasm. The lack of correlation between angiographic vasospasm and relaxation suggests that while the latter occurs after SAH, contractile processes may be more important in the pathogenesis of vasospasm.

Animals↗

PubMed1996

Relaxant effect of ketamine and its isomers on histamine-induced contraction of tracheal smooth muscle.

The mechanism by which racemic (R(+/-)) ketamine relaxes airway smooth muscle is unclear and there is no information on the differential effects of ketamine and its isomers. In this study, we have examined the spasmolytic effect of R(+/-) ketamine and its isomers S(+) and R(-) ketamine and the role of intracellular calcium and opioid receptors in R(+/-) ketamine-induced relaxation. The tension of isolated guinea pig tracheal strips was measured isometrically with a force displacement transducer and contraction elicited with histamine 10(-5) mol litre-1. In histamine-preconstricted strips, the two ketamine isomers (4.5-18.0 x 10(-4) mol litre-1) produced equipotent relaxation. A subthreshold dose of each isomer of ketamine (10(-4) mol litre-1) which alone did not relax histamine-induced contraction (S(+), P < 0.01; R(+/-), P < 0.01; R(-), P < 0.05) significantly potentiated adrenaline 1.25-5.0 x 10(-9) mol litre-1-induced relaxation (potency: S(+) > R(+/-) > R(-)). Increase in extracellular Ca2+ (1.8-14.4 x 10(-3) mol litre-1) significantly reduced R(+/-) ketamine-induced relaxation. S(-) Bay K 8644, at concentrations up to 2.0 x 10(-6) mol litre-1, partially antagonized R(+/-) ketamine-induced relaxation whereas at 10(-5) mol litre-1 or higher it potentiated the response. Naloxone 1.5-6.0 x 10(-6) mol litre-1 did not affect the relaxation caused by R(+/-) ketamine. We conclude that although both ketamine isomers produced equipotent spasmolytic effects on airway smooth muscle precontracted with histamine, they differed in their ability to potentiate the relaxing effect of adrenaline. S(+) ketamine produced the greatest potentiation. Changes in intracellular Ca2+ level secondary to a reduction in the L-type Ca2+ current may partially mediate the spasmolytic effect of R(+/-) ketamine.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2004

Influence of relaxin on the neurally induced relaxant responses of the mouse gastric fundus.

The peptide hormone relaxin has been reported to depress the amplitude of contractile responses in the mouse gastric fundus by upregulating nitric oxide (NO) biosynthesis at the neural level. In the present study, we investigated whether relaxin also influenced nonadrenergic, noncholinergic (NANC) gastric relaxant responses in mice. Female mice in proestrus or estrus were treated for 18 h with relaxin (1 microg s.c.) or vehicle (controls). Mechanical responses of gastric fundal strips were recorded via force-displacement transducers. In carbachol precontracted strips from control mice and in the presence of guanethidine, electrical field stimulation (EFS) elicited fast relaxant responses that may be followed by a sustained relaxation. All relaxant responses were abolished by tetrodotoxin. Relaxin increased the amplitude of the EFS-induced fast relaxation without affecting either the sustained one or the direct smooth muscle response to papaverine. In the presence of the NO synthesis inhibitor L-N(G)-nitro arginine (L-NNA), that abolished the EFS-induced fast relaxation without influencing the sustained one, relaxin was ineffective. In strips from relaxin-pretreated mice, EFS-induced fast relaxations were enhanced in amplitude with respect to the controls, while sustained ones as well as direct smooth muscle responses to papaverine were not changed. Further addition of relaxin to the bath medium did not influence neurally induced fast relaxant responses, whereas L-NNA did. In conclusion, in the mouse gastric fundus, relaxin enhances the neurally induced nitrergic relaxant responses acting at the neural level.

Adrenergic Agents↗

PubMed1997

The relaxing effect of ketamine on isolated rabbit lower esophageal sphincter.

We used ketamine to investigate the effects and intracellular mechanisms of several anesthetics on strips of lower esophageal sphincter (LES) from rabbits. Ketamine induced dose-dependent relaxation of LES preparations. It increased the content of 3',5'-cyclic adenosine monophosphate (cAMP) dose-dependently, but decreased that of 3',5'-cyclic guanosine monophosphate (cGMP). Pretreatment with nicotinic acid, an inhibitor of adenylate cyclase, along with atropine to block neurogenic effects, antagonized ketamine-induced relaxation. Pretreatment with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89), a selective antagonist for cAMP-dependent protein kinase, similarly antagonized the relaxant effect of ketamine. Cholera toxin and dibutyryl cAMP induced LES relaxation. However, dibutyryl cGMP induced little LES relaxation, and pretreatment with NG-nitro-L-arginine or methylene blue did not alter the relaxant effect. Atropine, propranolol, phentolamine, vasoactive intestinal peptide (VIP) antagonist, and tetrodotoxin did not affect the ketamine-induced relaxation. This response, however, was potentiated in the presence of indomethacin or diphenhydramine. Ketamine-induced relaxation was inhibited in the presence of verapamil. These findings suggest that ketamine induces relaxation of LES, in part, by modulating the activity of adenylate cyclase and in part by inhibiting transmembrane influx of Ca2+.

Adenylyl Cyclases↗

PubMed2000

Role of K+ channels in augmented relaxations to sodium nitroprusside induced by mexiletine in rat aortas.

BACKGROUND: A class Ib antiarrhythmic drug, mexiletine, augments relaxations produced by adenosine triphosphate (ATP) sensitive K+ channel openers in isolated rat aortas, suggesting that it produces changes in the vasodilation mediated by ATP-sensitive K+ channels. Nitric oxide can induce its vasodilator effect via K+ channels, including ATP-sensitive K+ channels, in smooth muscle cells. Effects of mexiletine on arterial relaxations to nitric oxide donors, have not been studied. Therefore, the current study in isolated rat aortas was designed to (1) evaluate whether mexiletine augments relaxation in response to nitric oxide donors, including sodium nitroprusside, and (2) determine the role of K+ channels in mediating effects of mexiletine on such nitric oxide-mediated relaxation. METHODS: Rings of rat aortas without endothelia were suspended for isometric force recording. Concentration-response curves of sodium nitroprusside (10(-10) to 10(-5) M) and 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7; 10(-9) to 10(-5) M) were obtained in the absence and in the presence of mexiletine, in combination with a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo [4,3,-a]quinoxaline-1-one (ODQ), or inhibitors for ATP-sensitive K+ channels (glibenclamide), inward rectifier K+ channels (BaCl2), delayed rectifier K+ channels (4-aminopyridine), large conductance Ca2+-dependent K+ channels (iberiotoxin), or small conductance Ca2+-dependent K+ channels (apamin). RESULTS: Mexiletine (10(-5) or 3 x 10(-5) M) augmented relaxations to sodium nitroprusside and NOC-7. In arteries treated with glibenclamide (10(-5) M), mexiletine (3 x 10(-5) M) did not affect relaxations to nitric oxide donors, whereas mexiletine augmented relaxations to sodium nitroprusside despite the presence of BaCl2 (10(-5) M), 4-aminopyridine (10(-3) M), iberiotoxin (5 x 10(-8) M) and apamin (5 x 10(-8) M). Relaxations to sodium nitroprusside were abolished by ODQ (5 x 10(-6) M), whereas these relaxations were augmented by mexiletine (3 x 10(-5) M) in arteries treated with ODQ (5 x 10(-6) M). CONCLUSIONS: These results suggest that ATP-sensitive K+ channels in vascular smooth muscle, contribute to the augmented vasodilator effect of a nitric oxide donor, sodium nitroprusside induced by mexiletine, and that the vasodilator effect is produced, at least in part, via the guanylate cyclase-independent mechanism.

Animals↗