Potentiated vasoconstrictor response to vasopressin following meclofenamate in conscious rats.
Experiments were performed to test the hypothesis that release of vasodilator cyclooxygenase products may attenuate the systemic and renal vasoconstrictor responses to arginine vasopressin (AVP) in the conscious, chronically instrumented rat. Four groups of animals were studied under the following conditions: (i) AVP infused iv at 2 ng/min for 40 min followed by a 15-min postcontrol; (ii) pretreatment with meclofenamate (3 mg/kg iv) followed by AVP infusion; (iii) meclofenamate pretreatment followed by saline vehicle infusion; and (iv) saline vehicle infusion alone (time control). AVP increased mean arterial blood pressure (MABP) in both meclofenamate-treated (n = 12) and untreated (n = 12) animals; however, the pressor response was significantly greater in animals with cyclooxygenase inhibition. Both heart rate (HR) and cardiac output (CO) (n = 6) fell during AVP infusion, but there were no differences between the meclofenamate-treated and the untreated groups. However, the total peripheral resistance response to AVP was significantly greater in animals treated with meclofenamate than the untreated group. Renal blood flow (RBF) was not affected by AVP infusion alone, but RBF fell significantly in animals given AVP after cyclooxygenase inhibition. The renal vascular resistance response to AVP was also enhanced by cyclooxygenase inhibition. There were no changes in any of the hemodynamic variables in either of the control protocols (i.e., meclofenamate alone or vehicle). These data demonstrate a consistent effect of cyclooxygenase inhibition to augment the systemic and renal vasoconstrictor responses to AVP, and suggest that endogenous vasodilator prostaglandins attenuate the potent vasoconstrictor action of this peptide in vivo.
Walker
B R
BR
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Brizzee
B L
BL
Harrison-Bernard
L M
LM
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D062367:ortho-Aminobenzoates; D001127:Arginine Vasopressin; D008469:Meclofenamic Acid