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Biomedical subjects

P Medina

Publications and source records attributed to P Medina.

At least 37 records · Page 2Linked to original sources
PubMed2000

Contractile effects of arginine analogues on human internal thoracic and radial arteries.

OBJECTIVES: Plasma levels of endogenous guanidino-substituted analogues of L -arginine are increased in various pathologic conditions. In the present study we determined the effects of some of these compounds on basal and stimulated release of nitric oxide in human internal thoracic and radial arteries. METHODS: Rings of human internal thoracic and radial arteries were obtained from 16 multiorgan donors. The rings were suspended in organ baths for isometric recording of tension. RESULTS: N(G)-monomethyl L -arginine (10(-6) to 10(-3) mol/L) and N(G),N(G)-dimethyl L -arginine (10(-6) to 10(-3) mol/L) caused concentration- and endothelium-dependent contractions. Maximal force of contractions for N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine in the internal thoracic artery were 18.0% +/- 4.3% and 17.8% +/- 3.8%, respectively, of the contraction to 100 mmol/L KCl, and those found in the radial artery were 9.6% +/- 2.5% and 9.1% +/- 2.4%, respectively. Aminoguanidine (10(-5) to 3 x 10(-3) mol/L) and methylguanidine (10(-5) to 3 x 10(-3) mol/L) produced endothelium-independent contractions. L -Arginine (10(-3) mol/L) prevented the contractions by N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine but did not change contractions induced by aminoguanidine and methylguanidine. N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine inhibited, in a concentration-dependent manner, the endothelium-dependent relaxation to acetylcholine in the internal thoracic artery and had little attenuating effect in the radial artery; aminoguanidine and methylguanidine were without effect. CONCLUSIONS: The results suggest that the contractions induced by N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine are due to inhibition of both basal and stimulated nitric oxide production, whereas aminoguanidine and methylguanidine do not affect the synthesis of nitric oxide. An increase in the plasma concentration of N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine is likely to represent a risk factor for abnormal vasomotor tone in conduit arteries used as coronary grafts.

Adolescent↗
PubMed2000

Prostate-specific antigen complexed to alpha(1)-antichymotrypsin in the early detection of prostate cancer.

OBJECTIVES: To study the usefulness of the complexed-to-total (C:T) prostate-specific antigen (PSA) ratio in the early detection of prostate cancer in patients with a total PSA value <4.0 ng/ml. PATIENTS AND METHODS: Total PSA and PSA complexed to alpha(1)-antichymotrypsin were measured in plasma from 193 men with benign prostatic hyperplasia (BPH) and 34 with prostate cancer. The diagnosis was confirmed in 28 BPH and 16 prostate cancer patients by biopsy and in 165 BPH and 18 prostate cancer patients by histological study following transurethral prostatectomy or open prostatectomy. RESULTS: The area under the receiver operating characteristic (ROC) curve was significantly greater for the C:T PSA ratio (0.908) than for total PSA (0.692) (p<0.001). Using a cut-off point of 0.83 for the C:T PSA ratio and regardless of the digital rectal examination (DRE) finding, 20 of the 34 prostate cancer patients would have been given a correct diagnosis (59% sensitivity) and in only 8 of the 193 BPH patients would a biopsy have been necessary (96% specificity). With a cut-off of 0.79, the sensitivity increased to 85% with a specificity of 92%. When the analysis was restricted to the 44 patients with abnormal DRE, the area under the ROC curve for the C:T PSA ratio was 0.919, and a cut-off point of 0. 78 gave a sensitivity of 87% and a specificity of 93%. Using a cut-off of 0.63, all prostate cancers were detected (100% sensitivity) and 54% of the negative biopsies would have been eliminated. For the 183 patients diagnosed following surgery, a cut-off of 0.82 gave a sensitivity of 72% and a specificity of 94%. CONCLUSION: Our results show that the C:T PSA ratio significantly improves the clinical utility of the PSA assay for detecting prostate cancer in patients with total PSA < 4 ng/ml, increasing the sensitivity without significantly increasing the number of biopsies.

Aged↗
PubMed1999

Modulation of adrenergic contraction of dog pulmonary arteries by nitric oxide and prostacyclin.

The aim of this work was to investigate the influence of endothelium-derived nitric oxide and prostaglandins on the contractile responses of isolated dog pulmonary arteries to electrical field stimulation and noradrenaline. Electrical field stimulation (1-8 Hz, 20 v, 0.25 ms duration, for 30 s) produced frequency-dependent contractions that were abolished by tetrodotoxin, guanethidine and, prazosin (all at 10(-6) M). Noradrenaline induced concentration-dependent contractions with an EC50, of 1.85 x 10(-6) M. The increases in tension induced by electrical stimulation and noradrenaline were of greater magnitude in arteries denuded of endothelium. In segments with endothelium, N(G)-nitro-L-arginine methyl ester (10(-4) M) or indomethacin (10(-5) M) had no effects on the basal tone, but significantly enhanced the neurogenic and noradrenaline-induced contractions. The potentiation by N(G)-nitro-L-arginine methyl ester of electrical stimulation-induced contractile responses was partially reversed by L-arginine (10(-4) M). In the presence of N(G)-nitro-L-arginine methyl ester together with indomethacin the electrical stimulation-induced contractile responses were higher than those obtained when only N(G)-nitro-L-arginine methyl ester or indomethacin was used. N(G)-nitro-L-arginine methyl ester and indomethacin did not influence neurogenic-induced contractile responses of endothelium-denuded arteries. The results suggest that endothelial cells of isolated dog pulmonary arteries depress the contractile response to electrical field stimulation of intramural nerves and that endothelium-derived dilator prostaglandins and nitric oxide may interact to inhibit contractile effects of adrenergic stimulation.

Animals↗
PubMed1999

V2-receptor-mediated relaxation of human renal arteries in response to desmopressin.

The effects of deamino-8-D-arginine vasopressin (desmopressin), a V2 receptor antidiuretic agonist, were studied in isolated rings from branches of renal arteries obtained from 22 patients undergoing nephrectomy. The rings were suspended in organ bath chambers for isometric recording of tension. In precontracted rings with norepinephrine (10(-6) to 3 x 10(-6) mol/L), desmopressin (10(-11) to 3 x 10(-7) mol/L) caused endothelium-dependent relaxation (81%+/-4% reversal of the initial contraction in arteries with endothelium; 20%+/-4% in arteries without endothelium; P < .05). The relaxation to desmopressin in rings with endothelium was reduced significantly by indomethacin (10(-6) mol/L) and unaffected by the inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (10(-4) mol/L). Two V1 receptor antagonists (a peptidic and a nonpeptidic) had no effect on desmopressin-induced relaxation. However, V2 receptor antagonists (three peptidic and a nonpeptidic) reduced significantly (P < .05) the maximal response to desmopressin. The results of this study show that desmopressin exerts powerful endothelium-dependent relaxation of human renal arteries, probably through stimulation of V2-like receptors that may bring about the release of dilating prostaglandins.

Adult↗
PubMed1999

Relaxant effects of antidepressants on human isolated mesenteric arteries.

AIMS: The therapeutic action of tricyclic agents may be accompanied by unwanted effects on the cardiovascular system. The evidence for the effects on vascular and nonvascular smooth muscle comes from animal studies. Whether these studies can be extrapolated to human vessels remains to be determined. Therefore, the present study was designed to investigate the influence of amitriptyline, nortriptyline and sertraline on the contractile responses of human isolated mesenteric arteries to electrical field stimulation, noradrenaline and potassium chloride. METHODS: Arterial segments (lumen diameter 0.8-1.2 mm) were obtained from portions of the human omentum during the course of 41 abdominal operations (22 men and 19 women), and rings 3 mm long were mounted in organ baths for isometric recording of tension. In some artery rings the endothelium was removed mechanically. RESULTS: In precontracted artery rings amitriptyline, nortriptyline and sertraline (3x10(-7)-10(-4) m ) produced concentration-dependent relaxation that was independent of the presence or absence of vascular endothelium. Incubation with indomethacin (3x10(-6) m ) reduced the pD2 values thus indicating the participation of dilating prostanoid substances in this response. Amitriptyline and nortriptyline inhibited both the neurogenic-and noradrenaline-induced contractions. In contrast, only the highest concentration of sertraline reduced the adrenergic responses. Amitriptyline, nortriptyline and sertraline inhibited contractions elicited by KCl and produced rightward shifts of the concentration-response curve to CaCl2 following incubation in calcium-free solution. CONCLUSIONS: These results indicate that amitriptyline and nortriptyline could act as adrenoceptor antagonists and direct inhibitors of smooth muscle contraction of human mesenteric arteries, whereas sertraline might principally exert its action only as direct inhibitor of smooth muscle contraction. This relaxant mechanism involves an interference with the entry of calcium.

Adult↗
PubMed1999

Effects of some guanidino compounds on human cerebral arteries.

BACKGROUND AND PURPOSE: Accumulation of endogenous guanidino-substituted analogues of L-arginine in chronic renal failure might contribute to some of the vascular and neurological disorders of this pathology. We tested the hypothesis that in human cerebral arteries, some guanidino compounds may increase vascular tone, through nitric oxide (NO) synthase inhibition, and impair endothelium-dependent relaxation. METHODS: Rings of human middle cerebral artery were obtained during autopsy of 26 patients who had died 3 to 12 hours before. The rings were suspended in organ baths for isometric recording of tension. We then studied the responses to N(G)-monomethyl-L-arginine (L-NMMA), N(G),N(G)-dimethyl-L-arginine (asymmetrical dimethylarginine; ADMA), aminoguanidine (AG), and methylguanidine (MG). RESULTS: L-NMMA (10(-6) to 3x10(-4) mol/L) and ADMA (10(-6) to 3x10(-4) mol/L) caused concentration- and endothelium-dependent contractions (median effective concentrations [EC(50)]=1.1x10(-5) and 1.6x10(-5) mol/L, respectively; E(max)=35. 5+/-7.9% and 43.9+/-5.9% of the response to 100 mmol/L KCl). AG (10(-5) to 3x10(-3) mol/L) and MG (10(-5) to 3x10(-3) mol/L) produced endothelium-independent contractions (E(max)=44.3+/-8.8% and 45.7+/-5.8% of the response to 100 mmol/L KCl, respectively). L-Arginine (10(-3) mol/L) prevented the contractions by L-NMMA and ADMA but did not change contractions induced by AG and MG. L-NMMA and ADMA inhibited endothelium-dependent relaxation induced by acetylcholine in a concentration-dependent manner; AG and MG were without effect. CONCLUSIONS: The results suggest that the contractions induced by L-NMMA and ADMA are due to inhibition of endothelial NO synthase activity, whereas AG and MG do not affect the synthesis of NO. An increase in the plasma concentration of L-NMMA and ADMA associated with uremia is likely to represent a diminished release or effect of NO, and consequently, an increased cerebrovascular tone in uremic patients is highly conceivable.

Adult↗
PubMed1999

Phase I clinical and pharmacologic study of 13-cis-retinoic acid, interferon alfa, and paclitaxel in patients with prostate cancer and other advanced malignancies.

PURPOSE: Recent studies demonstrate that retinoids decrease expression of the anti-apoptotic protein bcl-2, enhance the effect of chemotherapy, and act synergistically with interferon alfa (IFNalpha) to inhibit tumor cell growth in vitro. A phase I trial of 13-cis-retinoic acid (CRA), IFNalpha, and paclitaxel (TAX) was conducted to determine the toxicity and recommended phase II dose of this combination. Pharmacodynamic studies were performed to determine whether CRA and IFNalpha could modulate bcl-2 expression in vitro and in patients. PATIENTS AND METHODS: Twenty-two patients with prostate cancer or other advanced malignancies were treated with CRA/IFNalpha and escalating doses of TAX. The effect of CRA/IFNalpha on TAX pharmacokinetics was analyzed in both patients and human liver microsomes. The effect of CRA/IFNalpha on bcl-2 expression was assessed in vitro and in peripheral-blood mononuclear cells (PBMCs) by immunoblotting. RESULTS: CRA 1 mg/kg on days 1 to 4, IFNalpha 6 MU/m(2) subcutaneously on days 1 to 4, and TAX 175 mg/m(2) on day 3 was well tolerated. Pharmacokinetic studies demonstrated that CRA/IFNalpha caused a 33% decrease in TAX clearance and a 23% decrease in the area under the concentration-time curve values of the TAX metabolite 6-alfa-hydroxytaxol (6-HT). CRA alone reduced conversion of TAX to 6-HT by 41% in human liver microsomes. CRA/IFNalpha decreased bcl-2 expression in vitro and in PBMCs. CONCLUSION: CRA/IFNalpha and TAX is a well-tolerated regimen. CRA/IFNalpha increases TAX area under the concentration-time curve through an inhibitory effect of CRA on the metabolism of TAX to 6-HT. CRA/IFNalpha can modulate bcl-2 expression in vitro and demonstrates similar biologic activity in patients. Further studies will determine the activity of CRA/IFNalpha/TAX and validate the assessment of bcl-2 in PBMCs as a marker of tumor response.

Adult↗
PubMed1999

Comparative effects of dilator drugs on human penile dorsal artery and deep dorsal vein.

The present study was designed to characterize the response of human penile dorsal artery and deep dorsal vein to dilator drugs used in the diagnosis and treatment of erectile dysfunction with special emphasis on the effects on sympathetic neurotransmission. Ring segments of penile dorsal artery and deep dorsal vein were obtained from 20 multi-organ donors during procurement of organs for transplantation. The rings (3 mm long) were suspended in organ bath chambers for isometric recording of tension. We then studied the relaxant responses to prostaglandin E1 (PGE1), vasoactive intestinal peptide (VIP), papaverine (PV), sodium nitroprusside (SNP) and linsidomine chlorhydrate (SIN-1), and analysed the effects of these drugs on contractions induced by stimulation of perivascular sympathetic nerves. In artery and vein rings contracted by noradrenaline, all the drugs tested caused concentration-dependent relaxation. The order of potencies in terms of IC50 values (concentration of agonist causing 50% of the maximal relaxation) was PGE1=VIP>SNP>SIN-1=PV. Both arteries and veins contracted to electrical field stimulation (15 V, 0.5-2 Hz, 0.2 ms duration for 15 s) in a frequency-dependent manner. All relaxant drugs caused concentration-dependent inhibition of neurogenic contractions; the relative order of potencies was PGE1>VIP>SNP>SIN-1=PV. It is concluded that inhibition of sympathetic activity constitutes an effective relaxing mechanism in penile dorsal artery and vein. Modulation of sympathetic activity together with the direct effects on smooth muscle should be considered to evaluate adequately the efficacy of relaxant drugs to increase human penile blood supply.

Adolescent↗
PubMed1998

Vasopressin receptors involved in adrenergic neurotransmission in the circular muscle of the human vas deferens.

We studied the effects of vasopressin on the adrenergic responses of in vitro preparations of circular muscle from the vas deferens obtained from 28 men undergoing elective vasectomy. Vasopressin (3 x 10(-9)-3 x 10(-8) M) enhanced the phasic contractions elicited by electrical field stimulation and noradrenaline. This potentiation was blocked by the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)vasopressin (10(-6) M) but not by the vasopressin V2 receptor antagonist [d(CH2)5, D-Ile2,Ile4,Arg8]vasopressin (10(-6) M). The Ca2+ antagonist nifedipine (10(-6) M) did not affect the potentiation of electrical field stimulation induced by vasopressin and noradrenaline but reduced KCl-induced contractions and abolished the induction of phasic activity by vasopressin in the presence of KCl. The results demonstrate that vasopressin, in addition to its direct contractile effects, strongly potentiates contractions of human vas deferens elicited by adrenergic stimulation. Both the direct and indirect effects of vasopressin appear to be mediated by vasopressin V1 receptor stimulation and are independent of Ca2+ entry through dihydropyridine Ca2+ channels.

Adrenergic alpha-Agonists↗
PubMed1998

Arginine vasopressin enhances sympathetic constriction through the V1 vasopressin receptor in human saphenous vein.

BACKGROUND: Arginine vasopressin (AVP) not only acts directly on blood vessels through V1 receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments in vivo and in vitro. The aim of the present study was to investigate whether AVP can contribute to an abnormal adrenergic constrictor response of human saphenous veins. METHODS AND RESULTS: Saphenous vein rings were obtained from 32 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. AVP (3x10[-9] mol/L) enhanced the contractions elicited by electrical field stimulation at 1, 2, and 4 Hz (by 80%, 70%, and 60%, respectively) and produced a leftward shift of the concentration-response curve to norepinephrine (half-maximal effective concentration decreased from 6.87x10[-7] to 1.04x10[-7] mol/L; P<.05). The V1 vasopressin receptor antagonist d(CH2)5Tyr(Me)AVP (10[-6] mol/L) prevented the potentiation evoked by AVP. The selective V1 receptor agonist [Phe,2 Orn8]-vasotocin (3x[-10]-9 mol/L) induced potentiation of electrical stimulation-evoked responses, which was also inhibited in the presence of the V1 receptor antagonist (10[-6] mol/L). In contrast, the V2 receptor agonist desmopressin (10[-9] to 10[-7] mol/L) did not modify neurogenic responses, and the V2 receptor antagonist [d(CH2)5, D-Ile,2 Ile,4 Arg8]-vasopressin (10[-8] to 10[-6] mol/L) did not prevent the potentiation induced by AVP. The dihydropyridine calcium antagonist nifedipine (10[-6] mol/L) did not affect the potentiating effect of AVP. CONCLUSIONS: The results suggest that low concentrations of AVP facilitate sympathetic neurotransmission and potentiate constrictor effects of norepinephrine in human saphenous veins. These effects appear to be mediated by V1 receptor stimulation and are independent of calcium entry through dihydropyridine calcium channels. Thus, AVP may contribute to vascular mechanisms involved in acute ischemic syndromes associated with venous grafts, particularly if the sympathetic nervous system is activated.

Aged↗
PubMed1998

Neurogenic contraction and relaxation of human penile deep dorsal vein.

1. The aim of the present study was to characterize neurogenic and pharmacological responses of human penile deep dorsal vein and to determine whether the responses are mediated by nitric oxide from neural or endothelial origin. 2. Ring segments of human penile deep dorsal vein were obtained from 22 multiorgan donors during procurement of organs for transplantation. The rings were suspended in organ bath chambers for isometric recording of tension. We then studied the contractile and relaxant responses to electrical field stimulation and to vasoactive agents. 3. Electrical field stimulation (0.5-2 Hz) and noradrenaline (3 x 10(-10)-3 x 10(-5) M) caused frequency- and concentration-dependent contractions that were of greater magnitude in veins denuded of endothelium. The inhibitor of nitric oxide synthesis NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, l0(-4) M) increased the adrenergic responses only in rings with endothelium. 4. In preparations contracted with noradrenaline in the presence of guanethidine (10(-6) M) and atropine (10(-6) M), electrical stimulation induced frequency-dependent relaxations. This neurogenic relaxation was prevented by L-NAME, methylene blue (3 x 10(-5) M) and tetrodotoxin (10(-6) M), but was unaffected by removal of endothelium. 5. Acetylcholine (10(-8)-3 x 10(-5) M) and substance P (3 x 10(-11) -3 x 10(-7) M) induced endothelium-dependent relaxations. In contrast, sodium nitroprusside (10(-9)-3 x 10(-5) M) and papaverine (10(-8) 3 x 10(-5) M) caused endothelium-independent relaxations. 6. The results provide functional evidence that the human penile deep dorsal vein is an active component of the penile vascular resistance through the release of nitric oxide from both neural and endothelial origin. Dysfunction in any of these sources of nitric oxide should be considered in some forms of impotence.

Acetylcholine↗
PubMed1998

Role of vasopressin on adrenergic neurotransmission in human penile blood vessels.

We have used in vitro preparations of human penile dorsal artery and deep dorsal vein from 20 multiorgan donors to investigate whether subpressor concentrations of vasopressin facilitate noradrenergic transmission in penile blood vessels. Vasopressin constricted penile dorsal arteries (pD2, 9.38 +/- 0.18) and deep dorsal veins (pD2, 9. 40 +/- 0.14) by activating V1 receptors. Vasopressin (10(-11) and 3 x 10(-11) M) caused concentration-dependent potentiation of the contractions elicited by electrical stimulation (15 V, 0.5-2 Hz, 0.2 msec duration for 15 sec) and produced leftward shifts of the concentration-response curve for norepinephrine. The V1 receptor antagonist d(CH2)5Tyr(Me)AVP (3 x 10(-9)-10(-7) M) induced concentration-dependent inhibitions of potentiation caused by vasopressin. In contrast, the V2 receptor antagonist [d(CH2)5,D-Ile2, Ile4,Arg8]-vasopressin (10(-8)-10(-7) M) did not prevent the potentiation induced by vasopressin. The results demonstrate that vasopressin exerts powerful constrictor action in human penile arteries and veins by direct stimulation of V1 receptors. In addition, vasopressin strongly potentiates the contractions to norepinephrine and stimulation of perivascular adrenergic nerves. Consequently, the direct contractile effects of vasopressin together with its amplifying effects on adrenergic-mediated constriction should be taken into consideration in the overall regulation of penile erection and in those states characterized by increased plasma vasopressin levels.

Adolescent↗
PubMed1997

Endothelium-dependent relaxation of human saphenous veins in response to vasopressin and desmopressin.

PURPOSE: The goal of this study was to determine the effects of vasopressin and the selective V2-receptor agonist desmopressin on human saphenous veins, with special emphasis on endothelium-mediated responses. METHODS: Human saphenous vein segments were obtained from 35 patients undergoing coronary bypass surgery. Paired segments, one normal and the other deendothelized by gentle rubbing, were mounted for isometric recording of tension in organ baths. Concentration-response curves to vasopressin and desmopressin were determined in the presence and in the absence of either the V1-receptor antagonist d(CH2)5Tyr (Me)AVP (10(-6) mol/L), the V1-V2-receptor antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (10(-6) mol/L), indomethacin (10(-6) mol/L), or NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10(-4) mol/L). RESULTS: In vein rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with a concentration of vasopressin producing half-maximal contractions (EC50) of 3.44 x 10(-8) mol/L. The vasopressin V1-receptor antagonist (10(-6) mol/L) displaced the control curve to vasopressin 9.86-fold to the right in a parallel manner. In precontracted vein rings previously treated with the V1-antagonist (10(-6) mol/L) vasopressin caused endothelium-dependent relaxations. This relaxation was reduced significantly by indomethacin (10(-6) mol/L) and unaffected by the V1-V2-receptor antagonist (10(-6) mol/L) or by L-NAME (10(-4) mol/L). Desmopressin caused endothelium-dependent relaxations in precontracted vein rings that were inhibited by the mixed V1-V2-receptor antagonist and by indomethacin, but not by the V1-antagonist or by pretreatment with L-NAME. CONCLUSIONS: These observations indicate that vasopressin exerts contractile effects on human saphenous vein by V1-receptor stimulation. Vasopressin causes dilatation of human saphenous vein only if V1-receptor blockade is present. This relaxation appears to be mediated by the release of relaxant prostaglandins, probably derived from endothelial cells, and is independent of V2-receptor stimulation or release of nitric oxide. Desmopressin elicits relaxation that is largely dependent on V2-receptor stimulation, which may bring about the release of dilating prostaglandins from the endothelial cells.

Adult↗
PubMed1997

4-hydroxynonenal-induced relaxation of human mesenteric arteries.

The effect of 4-hydroxynonenal (4-HNE), a circulating lipid peroxidation product, on the vascular tone of human mesenteric arteries is studied. 4-HNE promotes relaxation of human mesenteric arterial rings in a concentration-dependent manner. Removal of the endothelium or treatment with N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10(-4) M) partially prevented 4-HNE-induced relaxation, thus suggesting the intervention of nitric oxide from endothelial origin in the vascular effects of 4-HNE.

Adult↗
PubMed1997

Potentiation by vasopressin of adrenergic vasoconstriction in the rat isolated mesenteric artery.

1. The aim of the present study was to investigate in rat mesenteric artery rings whether low concentrations of vasopressin could modify the contractile responses to noradrenaline and electrical stimulation of perivascular nerves. 2. Vasopressin (10[10]-10[-7] M) caused concentration-dependent contractions (pD2 = 8.36+/-0.09). The V1-receptor antagonist d(CH2)5Tyr(Me)AVP (10[-9]-10[-8] M) produced parallel rightward shifts of the control curve for vasopressin. Schild analysis yielded a pA2 value of 9.83 with a slope of 1.10+/-0.14. 3. Vasopressin (3 x 10[-10] and 10[-9] M) caused concentration-dependent potentiation of the contractions elicited by electrical stimulation (2-8 Hz; 0.2 ms duration for 30 s) and produced leftward shifts of the concentration-response curve for noradrenaline. The V1-receptor antagonist induced concentration-dependent inhibitions of potentiation induced by vasopressin. The selective V1-receptor agonist [Phe2, Orn8]-vasotocin (3 x 10[10] and 10[-9] M) induced potentiation of electrical stimulation-evoked responses which was also inhibited in the presence of the V1 antagonist (10[-8] M). In contrast, the V2-receptor agonist deamino-8-D-arginine vasopressin (desmopressin 10[-8]-10[-7] M) did not modify the electrical stimulation-induced responses and the V2-receptor antagonist [d(CH2)5, D-Ile2, Ile4, Arg8]-vasopressin (10[-8]-10[-7] M) did not affect the potentiation evoked by vasopressin. 4. In artery rings contracted by 10(-6) M noradrenaline in the presence of 10(-6) M guanethidine and 10(-6) M atropine, electrical stimulation (2, 4 and 8 Hz) produced frequency-dependent relaxations which were unaffected by 10(-9) M vasopressin but abolished by 10(-6) M tetrodotoxin. 5. Vasopressin also potentiated contractions elicited by KCl and contractions induced by addition of CaCl2 to KCl depolarized vessels. The augmenting effects were inhibited by the V1 antagonist. 6. In the presence of the calcium antagonist nifedipine (10[-6] M), vasopressin failed to enhance the contractile responses to electrical stimulation, noradrenaline and KCl. 7. The results demonstrate that low concentrations of vasopressin strongly potentiate the contractions to adrenergic stimulation and KCl depolarization. This effect appears to be mediated by V1 receptor stimulation which brings about an increase in calcium entry through dihydropyridine-sensitive calcium channels.

Animals↗