EFFECTS OF N-G-NITRO-L-ARGININE METHYL-ESTER ON REGIONAL HEMODYNAMIC-RESPONSES TO MGSO4 IN CONSCIOUS RATS

1 We assessed regional haemodynamic responses to the vasodilator, MgSO 4, in the absence and presence of the nitric oxide synthase inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME), in conscious chronically instrumented Long Evans rats (n=9). 2 MgSO4 (loading dose 220 mu mol k g(-1)min(-1) for 7 min, maintenance dose 56 mu mol kg(-1)min(-1) for 7 min), alone, caused slight bradycardia and hypotension accompanied by reductions in renal and mesenteric flows, but a marked hyperaemic vas odilatation in the hindquarters (flow, Delta 54+/-6%, vascular conduct ance, Delta 77+/-5%). 3 L-NAME (183 nmol kg(-1) min(-1)) caused hypert ension (29+/-2 mmHg) accompanied by bradycardia (-51+/-6 beats min(-1) ) and reductions in how and vascular conductance in the renal (-18+/-4 % and -35+/-3%, respectively), mesenteric (-35+/-3% and -49+/-3%, resp ectively), and hindquarters (-26+/-3% and -42+/-3%, respectively) vasc ular beds. In the presence of L-NAME, the hypotensive and bradycardic effects of MgSO4 were still apparent, but its hindquarters hyperaemic vasodilator effect was significantly attenuated. 4 In order to determi ne if the inhibitory action of L-NAME on the hindquarters hyperaemic v asodilator action of MgSO4 was a non-specific effect, due to the chang e in baseline conditions caused by L-NAME, we also examined responses to MgSO4 in the presence of endothelin-1 (12.5 pmol kg(-1) min(-1)) or angiotensin II (50 pmol kg(-1) min(-1)). In the presence of either pe ptide, the overall effects of MgSO4 on hindquarters flow and vascular conductance were unchanged. 5 In a separate experiment (n = 8) we dete rmined that the inhibitory effect of L-NAME on the hyperaemic vasodila tor response to MgSO4 was prevented by L-arginine, and also demonstrat ed that the beta(2)-adrenoceptor antagonist, ICI 118551, caused signif icant inhibition of the hindquarters haemodynamic effects of MgSO4. 6 We conclude that the hindquarters haemodynamic effects of MgSO4 in con scious rats involve a substantial L-NAME-sensitive component which dep ends on activation of beta(2)-adrenoceptors, probably as a consequence of adrenal medullary adrenaline release.