Antagonism of vasopressin-induced coronary artery constriction by the vasopressin antagonist d(CH2)5Tyr(Me)-AVP.
d(CH2)5Tyr(Me)-AVP is a potent inhibitor of the systemic vasoconstrictor action of vasopressin (AVP). In order to examine the effectiveness of this agent in blocking AVP-induced coronary vasoconstriction, 11 pentobarbital-anesthetized mongrel dogs were instrumented for the measurement of left circumflex (LCX) coronary blood flow, systemic arterial blood pressure, heart rate, lead II electrocardiogram, left ventricular end-diastolic pressure, left ventricular developed pressure, and left ventricular +/- dP/dt. Direct injection of AVP (0.01-1 microgram) into the LCX produced a dose-dependent decrease in coronary artery blood flow (maximum reduction: 60.5 +/- 8.1% after 1 microgram), - dP/dt (maximum reduction: 41.8 +/- 5.3% after 1 microgram), and +dP/dt (maximum reduction: 14.6 +/- 5.3%), whereas a dose-dependent increase in left ventricular end-diastolic pressure was observed (maximum increase: 62.6 +/- 20.2%). No significant changes occurred in heart rate, mean blood pressure, or left ventricular developed pressure. Intravenous administration of d(CH2)5Tyr(Me)-AVP reduced (1 microgram/kg) or abolished (5 micrograms/kg) the effects of AVP on coronary blood flow +/-dP/dt and left ventricular end-diastolic pressure. In addition, doses of 1,2, and 5 micrograms/kg of d(CH2)5Tyr(Me)-AVP alone produced increases of LCX blood flow of 5.1 +/- 1.5, 2.0 +/- 0.7, and 6.8 +/- 1.7 ml/min, respectively (p less than 0.05). We conclude that d(CH2)5Tyr(Me)-AVP is effective in preventing the coronary artery constriction and hemodynamic sequelae of intracoronary administered AVP.
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D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014667:Vasopressins / Q000037:antagonists & inhibitors*
D014667:Vasopressins; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-