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 793 records · Page 44Linked to original sources

PubMed2003

Adrenomedullin-induced endothelium-dependent relaxation in porcine ciliary arteries.

PURPOSE: To investigate adrenomedullin-induced relaxation in isolated porcine ciliary arteries. METHODS: In a myograph system (isometric force measurement), precontracted vessels ( approximately 0.1 micro M U46619; thromboxane A(2) analogue or approximately 10 nM endothelin-1) were exposed, in a cumulative manner, to increasing concentrations of adrenomedullin (1 nM to 1 micro M) in the presence or absence of different drugs. Some experiments were conducted in vessels with nonfunctional (intentionally mechanically damaged) endothelium. RESULTS: Adrenomedullin evoked marked relaxation [maximum relaxation (Rel(max)): 85.5 +/- 3.0%; negative log M concentration inducing 50% of Rel(max) (pD(2)): 7.4 +/- 0.1] in comparison to time-controls (Rel(max): 19.2 +/-4.8%; P < 0.001). Relaxation was inhibited by 3 micro M CGRP[8-37] (CGRP(1) receptor antagonist; Rel(max): 27.2% +/- 5.3%; P < 0.001) but not by 3 micro M adrenomedullin[22-52] (presumed adrenomedullin receptor antagonist; P = 0.75). Adrenomedullin-induced relaxation was less pronounced in nonfunctional endothelium vessels (Rel(max): 67.6% +/- 3.1%; pD(2): 6.9 +/- 0.1; P < 0.01). In vessels with functional endothelium, relaxation was not significantly influenced by 0.1 mM N(G)-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthesis inhibitor), 10 micro M indomethacin (a cyclooxygenase inhibitor), or 10 micro M 17-octadecynoic acid (a cytochrome P(450) inhibitor). In contrast, relaxation was significantly inhibited by either 10 mM tetraethylammonium (nonselective potassium channel inhibitor; P < 0.01) or 50 nM apamin (small conductance potassium channel inhibitor), together with 50 nM charybdotoxin (large and intermediate potassium channel inhibitor; P < 0.01). In the presence of these potassium channel inhibitors, the amount of relaxation was not significantly different (P > 0.50) from that observed in vessels with nonfunctional endothelium. CONCLUSIONS: In isolated porcine ciliary arteries, adrenomedullin induces relaxation that involves CGRP(1) receptors and is in part endothelium dependent. Endothelium-dependent relaxation was blocked by some potassium channel inhibitors, suggesting the possible release of an endothelium-derived hyperpolarizing factor (EDHF).

Adrenomedullin↗

PubMed1999

Endothelium-Independent Relaxation of Vascular Smooth Muscle by 17beta-Estradiol.

BACKGROUND: Estrogens directly dilate arteries, and this acute relaxation of vascular smooth muscle (VSM) may contribute to the cardioprotective effect of this important hormone. However, the mechanism by which estrogens relax VSM is not clear. METHODS AND RESULTS: Based on observations in isolated smooth muscle cells, we hypothesized that 17beta-estradiol (E(2)) causes dilation through receptor-mediated activation of K(+) channels in VSM cells. To test this hypothesis, E(2)-relaxation was studied in arteries from male Sprague-Dawley rats. We observed that the estrogen receptor antagonist, tamoxifen (3 µmol) attenuated E(2) relaxation, suggesting that at least a portion of the relaxation depends on activation of E(2) receptors. The nitric oxide synthase inhibitor, Nomega-nitro-larginine (100 µmol) did not affect E(2) relaxation in either denuded or endothelium-intact arterial strips. Furthermore, inhibition of guanylyl cyclase with LY83583 (10 µmol) had no effect on the relaxation, suggesting that nitric oxide does not contribute to this relaxation. Vascular segments contracted with 90 mmol KCl to disrupt the K(+) gradient had a similar E(2) relaxation does not require K(+)-channel activation. Finally, E(2) pretreatment inhibited contraction of arterial segments depleted of intracellular calcium but in the presence of extracellular calcium. However, E(2) did not affect contraction of strips in calcium-free solution. CONCLUSIONS: These final experiments suggest that E(2) inhibits Ca(2+) influx but not intracellular calcium release. Together, these studies establish that E(2) causes receptor-mediated relaxation of peripheral resistance arteries through inhibition of calcium entry independent of nitric oxide production, guanylyl cyclase stimulation, and K(+)-channel activation.

Journal Article↗

PubMed2004

Acetylcholine-induced relaxation and hyperpolarization in small bovine adrenal cortical arteries: role of cytochrome P450 metabolites.

The present study characterizes the vascular responses of isolated small bovine adrenal cortical arteries to acetylcholine, an endogenous neurotransmitter in the adrenal gland. Acetylcholine (10(-10) to 10(-6) m) elicited a concentration-dependent relaxation, with a maximal relaxation of 96 +/- 1% and EC50 of 4.2 nm. The relaxation was abolished by endothelial removal and attenuated by the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA, 30 microm) but not by the cyclooxygenase inhibitor indomethacin (10 microm). The maximal relaxation and EC50 of acetylcholine in the presence of L-NA were 87 +/- 4% and 22 nm, respectively. The acetylcholine-induced, indomethacin- and L-NA-resistant relaxation was eliminated by high K+ and markedly inhibited by the cytochrome P450 inhibitors SKF 525A (10 microm) and miconazole (10 microm). The maximal relaxations and EC50s with SKF 525A and miconazole were 56 +/- 8 and 72 +/- 2% and 0.8 and 0.5 microm, respectively. In indomethacin- and L-NA-treated arteries, acetylcholine induced a smooth muscle hyperpolarization, which was blocked by SKF 525A (3 +/- 1 mV vs. 15 +/- 2 mV of control). Arachidonic acid (10(-9) to 10(-5) m) and 14,15-epoxyeicosatrienoic acid (14,15-EET, 10(-9) to 10(-5) m), a cytochrome P450 metabolite of arachidonic acid, also evoked relaxations in small adrenal arteries, with maximal relaxations of 56 +/- 4 and 90 +/- 5%, respectively. The arachidonic acid-induced relaxation was blocked by SKF 525A. Using high-pressure liquid chromatography and gas chromatography/mass spectrometry analysis, EETs were identified in small adrenal arteries. These results demonstrate that acetylcholine is a potent vasodilator of small adrenal cortical arteries. The acetylcholine-induced relaxation is largely mediated by an endothelium-dependent hyperpolarization mechanism, presumably through cytochrome P450 metabolites of arachidonic acid.

Acetylcholine↗

PubMed1982

Asynchronous relaxation of the ischemic left ventricle.

The etiology and clinical significance of asynchronous relaxation of the left ventricle during isovolumic relaxation period was studied. Fifty patient with angina pectoris, 50 with myocardial infarction, 40 with normal heart, 20 with mitral stenosis and 10 with mitral prolapse syndrome were investigated. Asynchronous relaxation was observed in the following order: 72% in angina pectoris, 46% in myocardial infarction, 30% in mitral valve prolapse and 10% in both pure mitral stenosis and normal heart. In left anterior descending coronary artery disease, asynchronous relaxation was observed in 80%. Asynchronous relaxation seen before aortocoronary bypass graft to the left anterior descending coronary artery either disappeared or decreased after surgery. The contractility of the site, where asynchronous relaxation was seen, was normal in most cases and akinetic in none. The results of this study suggest the possibilities that asynchronous relaxation is at least partially related to localized myocardial ischemia and that it may be an early phenomenon of the effect of myocardial ischemia. With regard to asynchronous relaxation and hemodynamic alterations, force-velocity lissajous was analysed. Distortion of the lissajous in relaxation phase was seen in 73% who showed asynchrony. This distortion can be interpreted as indication of ununiformity of the left ventricular relaxation.

Angina Pectoris↗

PubMed1998

Endothelium-independent relaxant effect of 5-hydroxytryptamine (5-HT) on the isolated rabbit facial vein.

The facial vein in several species has been shown to have unusual properties, including exhibition of spontaneous myogenic tone and relaxation to norepinephrine (NE). The present study was undertaken to characterize the relaxant effect of 5-hydroxytryptamine (5-HT) on the rabbit facial vein. An isolated ring preparation of the rabbit facial vein exhibited intrinsic tone when it was stretched and the spontaneous contraction continued for hours. 5-HT concentration-dependently relaxed facial veins exhibiting spontaneous contraction. The relaxation was not inhibited by rubbing the endothelium or by NG-nitro-L-arginine (10(-4) M), a nitric oxide (NO) synthase inhibitor. The 5-HT-induced relaxation was also unaffected by pretreatment with indomethacin (10(-5) M), a cyclooxygenase inhibitor, and propranolol (10(-6) M), a both beta-adrenoceptor and 5-HT18-receptor antagonist. In contrast, 5-HT-induced relaxation of the facial vein was concentration-dependently antagonized by methysergide (10(-7) M and 10(-6) M), a non-selective 5-HT1- and 5-HT2-receptor antagonist, but not by NAN-190 (10(-6) M) and SDZ-205,557 (10(-6) M), antagonists for 5-HT1A- and 5-HT4-receptors, respectively. A higher (10(-6) M), but not lower (3 x 10(-7) M) concentration of ketanserin, a 5-HT2-receptor antagonist, slightly inhibited the 5-HT-induced relaxation. These results indicate that 5-HT-induced relaxation is not due to indirect mechanisms mediated by NE released from the sympathetic nerve terminals, or by endogenous prostanoid and endothelium-derived relaxing factor (EDRF = NO) released from the vascular tissues, but due to a direct effect on the 5-HT receptors located on vascular smooth muscle cells. However, the subtype of 5-HT receptor that produces relaxation of the rabbit facial vein remains to be clarified.

Animals↗

PubMed2004

Musculoskeletal MRI at 3.0 T: relaxation times and image contrast.

OBJECTIVE: The purpose of our study was to measure relaxation times in musculoskeletal tissues at 1.5 and 3.0 T to optimize musculoskeletal MRI methods at 3.0 T. MATERIALS AND METHODS: In the knees of five healthy volunteers, we measured the T1 and T2 relaxation times of cartilage, synovial fluid, muscle, marrow, and fat at 1.5 and 3.0 T. The T1 relaxation times were measured using a spiral Look-Locker sequence with eight samples along the T1 recovery curve. The T2 relaxation times were measured using a spiral T2 preparation sequence with six echoes. Accuracy and repeatability of the T1 and T2 measurement sequences were verified in phantoms. RESULTS: T1 relaxation times in cartilage, muscle, synovial fluid, marrow, and subcutaneous fat at 3.0 T were consistently higher than those measured at 1.5 T. Measured T2 relaxation times were reduced at 3.0 T compared with 1.5 T. Relaxation time measurements in vivo were verified using calculated and measured signal-to-noise results. Relaxation times were used to develop a high-resolution protocol for T2-weighted imaging of the knee at 3.0 T. CONCLUSION: MRI at 3.0 T can improve resolution and speed in musculoskeletal imaging; however, interactions between field strength and relaxation times need to be considered for optimal image contrast and signal-to-noise ratio. Scanning can be performed in shorter times at 3.0 T using single-average acquisitions. Efficient higher-resolution imaging at 3.0 T can be done by increasing the TR to account for increased T1 relaxation times and acquiring thinner slices than at 1.5 T.

Adult↗

PubMed1999

Mechanisms of endothelium-dependent relaxation in myometrial resistance vessels and their alteration in preeclampsia.

OBJECTIVE: To investigate the importance of prostacyclin and nitric oxide synthesis in endothelium-dependent relaxation in myometrial resistance vessels, and to test the hypothesis that a deficiency in nitric oxide synthesis contributes to the known alterations in endothelial function in preeclampsia. METHODS: Thirty-six women with normal pregnancies and 14 with preeclampsia had the myometrium biopsied at cesarean section. Resistance arteries were dissected and mounted on a wire myograph. After preconstriction with vasopressin, vessels were treated cumulatively with bradykinin. The process was repeated in the presence of indomethacin and then indomethacin and NG-monomethyl-L-arginine (L-NMMA). RESULTS: The vessels from women with normal pregnancies showed endothelium-dependent relaxation to bradykinin which was not significantly altered by the presence of indomethacin. The addition of L-NMMA significantly, but only partially, reduced the relaxation to bradykinin in the presence of indomethacin (p = 0.03). The vessels from women with preeclampsia showed markedly reduced relaxation to bradykinin (p < 0.0001), as compared to vessels from normal pregnant women. Relaxation of vessels from women with preeclampsia was increased by the addition of indomethacin (p = 0.03) but was virtually eradicated by the presence of L-NMMA. CONCLUSIONS: Eicosanoid synthesis plays little part in the relaxation of normal pregnant myometrial vessels to bradykinin. Nitric oxide synthesis mediates part but not all of the endothelium-dependent relaxation. In preeclampsia, relaxation to bradykinin is reduced; inhibition of eicosanoid synthesis allows increased relaxation, and nitric oxide synthesis appears to mediate a greater proportion of the relaxation than in normal pregnant women.

Adult↗

PubMed2000

Association between medications that relax the lower esophageal sphincter and risk for esophageal adenocarcinoma.

BACKGROUND: The incidence of esophageal adenocarcinoma is increasing rapidly. Gastroesophageal reflux is a strong risk factor for this disease. The increase in incidence of esophageal adenocarcinoma coincided with the introduction of medications that promote reflux by relaxing the lower esophageal sphincter (LES), such as nitroglycerin, anticholinergics, beta-adrenergic agonists, aminophyllines, and benzodiazepines. OBJECTIVE: To test the possible association between use of LES-relaxing medications and risk for adenocarcinoma of the esophagus and gastric cardia. DESIGN: A nationwide population-based case-control study with in-person interviews. SETTING: Sweden, 1995 through 1997. PATIENTS: 189 patients with newly diagnosed esophageal adenocarcinoma, 262 with adenocarcinoma of the gastric cardia, and 167 with esophageal squamous-cell carcinoma were compared with 820 population-based controls. MEASUREMENTS: Estimated incidence rate ratios, calculated by using multivariate logistic regression from case-control data with adjustment for potential confounding. RESULTS: Past use of LES-relaxing drugs was positively associated with risk for esophageal adenocarcinoma. Among daily, long-term users (>5 years) of LES-relaxing drugs, the estimated incidence rate ratio was 3.8 (95% CI, 2.2 to 6.4) compared with persons who had never used these drugs. Drugs of all classes contributed to the increased risk, but the association was particularly strong for anticholinergics. Short-term use of other types of LES-relaxing drugs did not seem to be strongly associated with risk. The association almost disappeared after adjustment for reflux symptoms, indicating that promotion of reflux is the link between use of LES-relaxing drugs and esophageal adenocarcinoma. If 15,490 men in any age group take LES-relaxing drugs daily for 5 years, 1 additional case of adenocarcinoma would be expected (number needed to treat for harm); in men older than 60 years of age, the number needed to treat for harm is 5,570. Assuming a causal relation, about 10% of the esophageal adenocarcinomas occurring in the population may be attributable to intake of LES-relaxing drugs. Cardia adenocarcinoma and esophageal squamous-cell carcinoma were not associated with use of LES-relaxing drugs. CONCLUSIONS: The widespread use of LES-relaxing drugs may have contributed to the increasing incidence of esophageal adenocarcinoma.

Adenocarcinoma↗

PubMed1999

Techniques for evaluation of right ventricular relaxation rate in horses and effects of inhalant anesthetics with and without intravenous administration of calcium gluconate.

OBJECTIVES: To determine the most repeatable method for evaluating right ventricular relaxation rate in horses and to determine and compare effects of isoflurane or halothane with and without the added influence of intravenously administered calcium gluconate on right ventricular relaxation rates in horses. ANIMALS: 6 Thoroughbred horses from 2 to 4 years old. PROCEDURE: 6 models (2 for monoexponential decay with zero asymptote, 3 for monoexponential decay with variable asymptote, and 1 for biexponential decay) for determining right ventricular relaxation rate were assessed in conscious and anesthetized horses. The 2 methods yielding the most repeatable results then were used to determine right ventricular relaxation rates in horses anesthetized with isoflurane or halothane before, during, and after i.v. administration of calcium gluconate. Right ventricular pressure was measured, using a catheter-tip high-fidelity pressure transducer, and results were digitized at 500 Hz from minimum rate of change in ventricular pressure. RESULTS: 2 models that used monoexponential decay with zero asymptote repeatedly produced an estimate for relaxation rate and were used to analyze effects of anesthesia and calcium gluconate administration on relaxation rate. Isoflurane and halothane each prolonged right ventricular relaxation rate, with greater prolongation evident in halothane-anesthetized horses. Calcium gluconate attenuated the anesthesia-induced prolongation in right ventricular relaxation rate, with greater response obtained in isoflurane-anesthetized horses. CONCLUSIONS AND CLINICAL RELEVANCE: Right ventricular relaxation rate in horses is assessed best by use of a monoexponential decay model with zero asymptote and nonlinear regression. Intravenous administration of calcium gluconate to isoflurane-anesthetized horses best preserves myocardial relaxant function.

Anesthetics, Inhalation↗

PubMed2000

Regulation of beta-adrenoceptor-mediated relaxation of the rat aorta is modulated by endogenous ovarian hormones.

The aim of this study was to assess the influence of the endogenous status of ovarian hormones on the relaxation induced by the beta-adrenoceptor agonists isoprenaline (isoproterenol) and dobutamine in thoracic aorta segments, precontracted with noradrenaline, from age-matched (13-week-old) virgin (oestrus) and ovariectomized (OVX) prepubertal female Wistar rats. Isoprenaline-induced relaxation was decreased in intact aortic segments from OVX rats compared with that in segments from oestrus rats. Relaxation was significantly reduced by endothelium removal, 1 micromol/l propranolol or 100 micromol/l N(G)-nitro-L-arginine methyl ester (L-NAME). The beta(1)-adrenoceptor agonist dobutamine induced less relaxation in intact arteries from oestrus rats than did isoprenaline, and dobutamine-induced relaxation was markedly less in intact segments from OVX compared with oestrus rats. This dobutamine-induced relaxation was abolished by endothelium removal, and reduced by 1 micromol/l propranolol, 100 micromol/l L-NAME or 1 micromol/l yohimbine. Cholera toxin (an activator of the stimulatory G-protein G(s)) caused relaxation in intact arteries from oestrus rats; this relaxation was decreased by both deprivation of ovarian hormones and endothelium removal. Forskolin (a direct activator of the catalytic subunit of adenylate cyclase) and sodium nitroprusside (a nitric oxide donor and cGMP-dependent vasodilator agonist) induced similar endothelium-independent relaxation in arteries from both oestrus and OVX rats. These results suggest that the relaxation elicited by endothelial beta-adrenoceptor activation in the rat thoracic aorta is impaired by deprivation of female ovarian hormones; this impairment is caused, at least in part, by decreases in both the endothelial release of NO and G(s) function.

Adrenergic beta-Agonists↗

PubMed2004

Relaxation behaviors of monolayers of octadecylamine and stearic acid at the air/water interface.

This study investigated the relaxation behaviors of octadecylamine (ODA), stearic acid (SA), and SA/ODA mixed monolayers at the air/water interface. Area relaxations of monolayers at constant surface pressure were studied by a nucleation and growth mechanism and by direct observation using a Brewster angle microscope (BAM). The results showed that ODA and SA monolayers exhibit different characteristics in the area loss and in the BAM morphology. In the initial relaxation stage, SA monolayer illustrates a more stable characteristic than ODA. But at the later stage, the area loss of SA monolayer increases more quickly than that for ODA due to significant nucleation and growth of 3D aggregates. The BAM results demonstrated that 3D aggregates of large scale domains are likely to form on a SA monolayer even when the area loss is insignificant. On the contrary, only dotlike aggregates of low density were found on the ODA monolayer when relaxation is carried out at higher surface pressure. The relaxation behavior of SA monolayer can be described by the Vollhardt model. However, the relaxation of ODA monolayer does not follow the nucleation model described by Vollhard but can reasonably be attributed to the effect of dissolution. For the SA/ODA mixed monolayers, the relaxation behaviors in the initial and final stages follow different mechanisms, which is attributed to the formation of distinct phases as observed from the BAM. This result also implied that SA and ODA are not completely miscible to be a homogeneous phase. Phases of various compositions were formed in the mixed monolayers, and thus, the relaxation mechanism was shifted during the relaxation process as dominated by different relaxation behaviors of various phases.

Journal Article↗

PubMed1990

Fluoride produces endothelium-dependent relaxation and endothelium-independent contraction in coronary artery.

NaF produced endothelium-dependent relaxation and endothelium-independent contraction in porcine, bovine, canine and human coronary artery rings precontracted with either KCl or prostaglandin F2 alpha. For practical reasons the porcine coronary artery was selected to investigate the mechanisms responsible for these responses. Methylene blue, indomethacin, N-ethylmaleimide, pertussis toxin and cholera toxin all significantly attenuated the endothelium-dependent relaxation caused by fluoride. Pretreatment with deferoxamine had no effect on relaxation and superoxide dismutase/catalase potentiated the relaxation produced by fluoride. Fluoride also contracted vessels with or without the endothelium to equal tension levels and had no apparent relaxing effect on basal tone. The contraction produced by fluoride was significantly attenuated by pertussis toxin and cholera toxin; however, none of the other agents examined significantly altered contraction. Bradykinin also caused endothelium-dependent relaxation and this response was significantly attenuated by methylene blue but not indomethacin. Therefore, fluoride appears to relax the arteries by releasing an endothelium-derived relaxing factor similar to that released by bradykinin (methylene blue sensitive) and one or more prostanoid type endothelium-derived relaxing factor(s) (indomethacin sensitive). Furthermore, fluoride relaxation and contraction may be guanine nucleotide-binding regulatory protein-mediated based on sensitivity to the guanine nucleotide-binding regulatory protein modulators.

Animals↗

PubMed1988

Stereoselective effect of diltiazem on endothelium-dependent relaxations in canine femoral arteries.

Experiments were designed to analyze potential interactions between voltage-dependent calcium channel blockers and endothelium-dependent vascular responses. Rings of canine femoral artery were suspended for isometric force recording in organ chambers and contracted with prostaglandin F2 alpha. Removal of the endothelium had no effect on relaxations induced by d-cis-diltiazem (active stereoisomer), verapamil or nimodipine. When rings with endothelium were first partially relaxed with acetylcholine or the calcium ionophore A23187 the concentration-relaxation curve to d-cis-diltiazem (but not to verapamil or nimodipine) was significantly shifted to the right. Partial relaxation of femoral arterial rings without endothelium by sodium nitroprusside had no effect on relaxations evoked by diltiazem. Pretreatment with diltiazem (10(-6) M) had no effect on endothelium-dependent relaxations to acetylcholine in femoral artery rings. D-cis-Diltiazem partially reversed the relaxation induced by acetylcholine in a bioassay system, in which a ring of canine coronary artery without endothelium was superfused by solution passing through a segment of femoral artery with endothelium. D-cis-Diltiazem relaxed the bioassay ring when infused downstream of the perfused femoral artery with, or upstream of a femoral artery without endothelium. The effect of diltiazem was stereoselective (the less active l-cis-diltiazem had no effect). Verapamil did not reverse the relaxation induced by acetylcholine and did not affect the reversal induced by diltiazem. These findings indicate that diltiazem specifically antagonizes the production and/or the release of endothelium-derived relaxing factor(s) stimulated by acetylcholine or A23187 in canine femoral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Possible involvement of 5-lipoxygenase products in the generation of endothelium-derived relaxing factor.

Acetylcholine and substance P applied to the donor tissue, dog femoral artery segments with endothelium, produced moderate relaxations of the assay tissue, endothelium-denuded dog coronary artery strips. The relaxation was attenuated markedly by treatment of the assay tissue with hydroquinone and abolished by oxyhemoglobin or methylene blue. In this bioassay system, the effect of AA861 and TMK777, new 5-lipoxygenase inhibitors, was evaluated. When the donor tissue was treated with AA861 or TMK777, the responses to acetylcholine and substance P were attenuated moderately, whereas the relaxation by nitroglycerin was not influenced by AA861. However, the inhibitors when infused just below the donor tissue did not attenuate relaxant responses to acetylcholine and substance P. Application of superoxide dismutase (SOD) to the donor tissue caused a relaxation of the assay tissue, and potentiated the relaxation by acetylcholine and substance P. AA861 and TMK777 suppressed the relaxant responses to acetylcholine and substance P, respectively, in the presence and absence of SOD to a similar extent and abolished the SOD-induced relaxation. Pyrogallol abolished the relaxation by acetylcholine, but did not inhibit the response when the donor tissue was pretreated with SOD. Therefore, it appears that AA861 and TMK777 do not degrade endothelium-derived relaxing factor (EDRF) in the perfusate via generation of superoxide anion or block the action of EDRF on vascular smooth muscle, but interfere with the synthesis and/or release of EDRF. The findings obtained so far support the idea that lipoxygenase products participate in the generation of EDRF.

Acetylcholine↗

PubMed1988

Endothelium-dependent contraction and -independent relaxation induced by adenine nucleotides and nucleoside in the canine basilar artery.

ATP, ADP, AMP and adenosine at 10(-8) induced a slight relaxation, and at concentrations greater than 10(-7) M caused a biphasic response consisting of an initial relaxation followed, after a brief period, by a transient contraction in canine basilar artery. ATP (10(-6) and 10(-5) M) caused a triphasic response consisting of a rapid, small contraction, a relaxation and then a second, transient contraction. The order of agonist potency for contraction was ATP greater than ADP much greater than AMP = adenosine, but for producing relaxation the agonists were equipotent. Removal of the endothelium abolished the contraction after the relaxation, but had virtually no effect on the relaxation and the rapid contraction induced by ATP (10(-6) and 10(-5) M). Only the relaxation in response to ATP (10(-6) M) was attenuated by removal of the endothelium. Aspirin (a cyclooxygenase inhibitor) (5 X 10(-5) M), OKY-046 (a thromboxane A2 synthetase inhibitor) (10(-5) M) and ONO-3708 (a thromboxane A2 antagonist) (5 X 10(-9) M) attenuated markedly the endothelium-dependent contraction induced by ATP (10(-5) M) and ADP (10(-5) M), but did not affect the relaxation. Phentolamine (10(-6) M) and atropine (10(-6) M) did not affect either the contraction or the relaxation. The relaxations induced by both ATP and adenosine in both endothelium-intact preparations and endothelium-removed preparations were attenuated by 8-phenyltheophylline (P1 antagonist) (10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

PubMedDate not supplied

NMR relaxation times of blood: dependence on field strength, oxidation state, and cell integrity.

The variation with field strength or interecho interval of the T1 and T2 relaxation times of oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), and methemoglobin (MHb) in either intact or lysed red blood cells was studied with a variable field (0.19-1.4 T) nuclear magnetic resonance spectroscopy unit. The T2 relaxation time of intracellular HbO2 decreased slightly with increasing field strength and interecho interval. The T2 relaxation times of intracellular Hb and MHb decreased markedly with increasing field strength and interecho interval. This T2 proton relaxation enhancement increased as the square of the applied field strength and was 1.6 times stronger for intracellular MHb than for intracellular Hb. The T2 relaxation enhancement is secondary to the loss of transverse phase coherence of water protons that diffuse across cellular magnetic field gradients. These field gradients occur when an external field is applied to a region with gradients of magnetic susceptibility. The heterogeneity of magnetic susceptibility is caused by the heterogeneous distribution (only intracellular) of the paramagnetic molecules (Hb or MHb). The T2 relaxation times of red cell lysates (homogeneous magnetic susceptibility) were independent of field strength or interecho interval. There was a decrease in the T1 relaxation times when the red cells were lysed. This may be due to an increase in the slow motional components of water molecules, because of the decrease in the average distance between water and hemoglobin molecules in the lysate. The T1 relaxation times of all the MHb samples were shortened because of proton-electron dipolar-dipolar relaxation enhancement. All the T1 relaxation times increased with increasing field strength.

Blood↗

PubMed1984

[Early relaxation of the left ventricular wall in coronary artery disease].

A mechanism for the genesis of early relaxation of the left ventricle was assessed. For 18 patients with coronary artery disease, biplane left coronary cineangiography was performed and the coordinates (x, y, z) of the points of the artery were measured by frame to frame basis throughout one cardiac cycle. The spatial distance (segment length) between any two points was calculated on each frame as (Formula: See text) to investigate shortening and relaxation characteristics of the ischemic and nonischemic segments. Coronary angiography was repeated during right atrial pacing to aggravate ischemia, and following nitroglycerin administration to ameliorate ischemia. From data of six normal subjects, 43 segments were calculated. All showed shortening during systole and lengthening in diastole. Right atrial pacing caused early relaxation in only two of the 43. Two hundred and fifteen segments were calculated for 18 patients with coronary artery disease. All but eight segments showed normal relaxation on control angiography. Following pacing, 115 segments showed early relaxation, and in 107 of the 115, normal relaxation were restored after nitroglycerin. Among the 107 segments, 44 were ischemic and 63 were normal. For 34 segments with early relaxation by pacing, pacing was repeated after administering nitroglycerin, and 15 did not reproduce early relaxation. The present study showed that early relaxation was observed in patients with coronary artery disease, which was effectively ameliorated by nitroglycerin, suggesting this phenomenon is closely related to the development of myocardial ischemia. The decreased active tension, reduced duration of tension, development and delay in electrical depolarization in the ischemic segment can be a reasonable inducement to early relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cineangiography↗

PubMed1998

Angiotensin 1-7 induces bradykinin-mediated relaxation in porcine coronary artery.

Angiotensin 1-7 (Ang 1-7) has been reported to induce relaxation which is partially blocked by a kinin receptor antagonist. We investigated the relationship between kinins and angiotensin peptides with use of preconstricted isolated pig coronary arteries. Ang 1-7 alone (up to 10(-5) M) had no relaxant effect. Bradykinin (BK) (10(-10)-10(-7) M) induced transient relaxation, returning to basal tone, although BK remained in the bath. In these BK-stimulated rings, Ang 1-7 but not BK (both 5 x 10(-6) M) again relaxed the rings by approximately 50%. This relaxation was blocked by a BK B2 antagonist, a kininase, and a nitric oxide synthase inhibitor. Ang 1-7 inhibited purified angiotensin-converting enzyme (ACE) by 30 +/- 3.5% (n = 4) at 10(-6) M. However, in BK-pretreated rings, the ACE inhibitor ramiprilat did not induce relaxation, nor did it affect the relaxant response to Ang 1-7, which suggests that the effect of Ang 1-7 was not caused by ACE inhibition. Ang 1-7-induced vasodilation was reduced by 69.9 +/- 6.2% by an AT2 receptor blocker, PD-123319, and 29.3 +/- 7.3% by an AT1 antagonist, losartan. Neither the nonselective AT1/AT2 receptor antagonist sarthran nor saralasin inhibited the response to Ang 1-7. Ang II did not elicit relaxation either alone or in the presence of losartan, which suggests that activation of AT2 receptors does not cause relaxation. Thus, in the presence of bradykinin, Ang 1-7 relaxes pig coronary arteries via a PD-123319-sensitive mechanism involving nitric oxide, kinins and the BK B2 receptor. The kallikrein-kinin and renin-angiotensin systems may be linked through the interaction of Ang 1-7 and BK.

Angiotensin I↗