Coronary vasoconstriction produced by vasopressin in anesthetized goats. Role of vasopressin V1 and V2 receptors and nitric oxide.
To examine the role of vasopressin V1 and V2 receptors, nitric oxide and prostanoids in the coronary vascular effects of [Arg8]vasopressin, coronary blood flow was measured with an electromagnetic flow transducer placed around the left circumflex (23 goats) or anterior descending (11 goats) coronary artery and vasopressin (0.03-1 microg) was intracoronarily injected in 34 anesthetized, open-chest goats. Basal mean values for coronary blood flow, mean systemic arterial pressure and heart rate, were 34 +/- 2.38 ml/min, 89 +/- 3.34 mmHg and 80 +/- 3.06 beats/min, respectively. Vasopressin produced dose-dependent decreases in coronary blood flow and the maximal reduction of this flow, attained with 1 microg of vasopressin, was 14 +/- 1.49 ml/min (42 +/- 2.64% of basal flow) (P < 0.01). Desmopressin (0.03-1 microg; 8 goats) did not affect significantly coronary blood flow. The intracoronary infusion of the antagonist for vasopressin V1 receptors d(CH2)5Tyr (Me) arginine vasopressin (2 microg/min per kg, 6 animals) significantly diminished the effects of vasopressin on coronary blood flow (the effects of 1 microg of vasopressin were reduced by 28%, P < 0.05). The mixed antagonist for vasopressin V1 and V2 receptors desGly-d(CH2)5-D-Tyr(Et)Val arginine vasopressin (0.2, 0.7 and 2 microg/min per kg, 9 animals) decreased in a dose-dependent manner the effects of vasopressin on coronary blood flow (the effects of 1 microg of vasopressin were decreased by 61% with 2 microg/min per kg, P < 0.01). Intracoronary infusion of saline (vehicle, 3 goats) did not change the effects of vasopressin on coronary blood flow. Intravenous administration of the inhibitor of nitric oxide synthesis N-omega-nitro-L-arginine methyl ester (L-NAME, 47 mg/kg, 9 animals) decreased resting coronary blood flow by 10% (P < 0.01) and augmented mean systemic arterial pressure by 20% (P < 0.01), without changing heart rate. During this treatment the reduction in coronary blood flow produced by vasopressin was higher than under control (the effects of 1 microg of vasopressin were increased by 28%, P < 0.01). Intravenous administration of the inhibitor of cyclooxygenase, meclofenamate (5 mg/kg, 7 animals), neither modified resting coronary blood flow, arterial pressure and heart rate nor the effects of vasopressin on this flow. These data indicate that vasopressin produces marked coronary vasoconstriction and suggest that: (a) it may be mediated by vasopressin V1 receptors, without involvement of vasopressin V2 receptors, (b) it is probably inhibited by nitric oxide under normal conditions and (c) it may be not modulated by prostanoids.
Fernández
N
N
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
García
J L
JL
García-Villalón
A L
AL
Monge
L
L
Gómez
B
B
Diéguez
G
G
D000768:Anesthesia, General; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006041:Goats; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008469:Meclofenamic Acid; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D017483:Receptors, Vasopressin / Q000187:drug effects*; D012076:Renal Agents / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D017483:Receptors, Vasopressin; D012076:Renal Agents; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D019001:Nitric Oxide Synthase; D003894:Deamino Arginine Vasopressin; D019331:NG-Nitroarginine Methyl Ester