EFFECTS OF NG-NITRO-L-ARGININE METHYL-ESTER OR INDOMETHACIN ON DIFFERENTIAL REGIONAL AND CARDIAC HEMODYNAMIC ACTIONS OF ARGININE VASOPRESSIN AND LYSINE VASOPRESSIN IN CONSCIOUS RATS

1 Measurements of changes in renal, mesenteric and hindquarters haemodynamics or cardiac haemodynamics in response to i.v. bolus doses of arginine vasopressin (AVP) or lysine vasopressin (LVP, 0.7 and 7.0 pmol) were made in conscious, chronically-instrumented Long Evans rats. 2 In some experiments AVP and LVP were administered during an infusion of N(G)-nitro-L-arginine methyl ester (L-NAME; 1.0 or 0.3 mg kg-1 h-1) to determine whether or not inhibition of nitric oxide production influenced the cardiovascular effects of the peptides. In other experiments, indomethacin (bolus dose of 5 mg kg-1 followed by infusion at 5 mg kg-1 h-1) was given to determine the possible involvement of cyclo-oxygenase products in the responses to AVP and LVP. 3 Under control conditions, the lower dose of LVP had significantly greater effects than AVP on heart rate, mean arterial blood pressure, renal, mesenteric and hindquarters conductances, total peripheral conductance, cardiac index, peak aortic flow and +dF/dt(max). The higher dose of LVP had significantly greater effects than AVP on all variables (i.e. including stroke index and central venous pressure). 4 In the presence of L-NAME (1 mg kg-1 h-1) there was a sustained increase in mean arterial blood pressure (+ 23 +/- 3 mmHg) and reductions in mesenteric (-38 +/- 4%) and hindquarters (-30 +/- 6%) vascular conductances. Under these conditions the difference in the pressor effects of AVP and LVP was abolished, but their differential effects on regional and cardiac haemodynamics persisted. This dose of L-NAME did not change cardiac baroreflex sensitivity. 5 During infusion of L-NAME at a lower rate (0.3 mg kg-1 h-1), baseline cardiovascular status was unchanged and regional haemodynamic effects of AVP and LVP were enhanced, but the differences in the regional vasoconstrictor responses to the two peptides persisted. 6 Indomethacin (5 mg kg-1 bolus, then 5 mg kg-1 h-1 infusion) augmented the renal vasoconstrictor responses to AVP and LVP, but abolished the difference in the hindquarters vasoconstrictor responses to the two peptides. However, the differences in the pressor and the renal and mesenteric vasoconstrictor effects of AVP and LVP still occurred in the presence of indomethacin. 7 The results indicate that AVP normally has lesser cardiovascular effects than LVP but this difference does not seem to be due to more effective stimulation of nitric oxide-mediated or cyclo-oxygenase-dependent vasodilator mechanisms by AVP than LVP.