1 Regional haemodynamic responses to i.v. bolus doses (0.1-10.Omgkg-) of N0-nitro-L-arginine methyl ester (L-NAME) were measured in conscious, Long Evans rats (n = 8) chronically instrumented with renal, mesenteric and hindquarters pulsed Doppler flow probes and intravascular catheters. 2 L-NAME caused dose-dependent pressor effects associated with renal, mesenteric and hindquarters vasoconstrictions. The mesenteric vascular bed showed earlier onset with more rapid, and greater, maximum vasoconstrictions than the renal or hindquarters vascular beds; however, the hindquarters vasoconstriction was more persistent. D-NAME was without significant effects (n = 2).3 Primed infusion of L-arginine (lOOmgkg-1 bolus followed by lOOmgkg-h-' infusion), starting 10min after an i.v. bolus injection of L-NAME (10mgkg-1), caused significant reversal of the pressor responses, and renal and mesenteric vasoconstrictions, but not of the hindquarters vasoconstriction.Primed infusions of L-arginine (100 mg kg 1, 100 mg kg'-h -1) starting 5 min after L-NAME (1 mg kg1 additionally caused some reversal of the hindquarters vasoconstriction, but this effect was transient.4 Primed infusion of L-arginine (lOOmgkg-', lOOmgkg-'h-1) starting 30min before i.v. bolus injection of L-NAME (10mgkg-') caused significant attenuation of the pressor effects and the renal and mesenteric vasoconstrictions but not of the hindquarters vasoconstriction. 5 In a separate group of rats (n = 8) chronically instrumented with thoracic aortic electromagnetic flow probes for the measurement of cardiac haemodynamics, i.v. bolus injection of L-NAME (10mgkg-1) produced significant reductions in total peripheral conductance, cardiac output, stroke volume, peak thoracic aortic flow and the maximum rate of rise of aortic flow; these were coincident with the maximum pressor and vasoconstrictor effects.6 These results, collectively, are consistent with L-NAME interfering with L-arginine-nitric oxide pathways that have important influences on regional vascular conductances in vivo. The pressor effect resulting from L-NAME-induced vasoconstrictions is offset by a substantial reduction in cardiac function that may depend on direct and/or indirect effects of L-NAME on the heart.

The regional hemodynamic consequences of inhibiting vascular endothelial nitric oxide generation with NG-monomethyl-L-arginine (L-NMMA) were studied in conscious Long-Evans rats. Experiments were carried out in groups of chronically instrumented rats with intravascular catheters and pulsed Doppler probes to monitor regional blood flow. L-NMMA (0.3-300 mg/kg) caused a dose-dependent, long-lasting (5-90 minutes), and enantiomerically specific increase in mean blood pressure and also caused bradycardia. The increase in blood pressure was accompanied by a dose-dependent and long-lasting vasoconstriction in the internal carotid, mesenteric, renal, and hindquarters vascular beds that could be attenuated, in a concentration-dependent manner, by L-arginine but not by D-arginine. In contrast, L-arginine did not affect the pressor or vasoconstrictor effects of vasopressin. These results indicate that nitric oxide production by vascular endothelial cells contributes to the maintenance of blood pressure and to the control of the resting tone of different vascular beds in the conscious rat.

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