The contribution of nitric oxide to cardiovascular status and responses to vasodilators in conscious, hypertensive, transgenic ((mRen-2)27) rats

1 The aim of the study was to measure the regional haemodynamic responses to vasodilators, and the effects of nitric oxide (NO) synthase inhibition, in conscious, hypertensive, transgenic ((mRen-2)27) rats (TG rats) and normotensive, Hannover Sprague-Dawley (SD) rats. 2 The hypotensive response to acetylcholine was greater in TG than in SD rats, but the renal vasodilator responses were not different. 3 The responses to bradykinin were similar in the two strains, except that hindquarters vasodilatation occurred only in SD rats. 4 Salbutamol caused smaller renal and hindquarters vasodilatation in TG rats than in SD rats, and there was mesenteric vasodilatation only in the latter strain. 5 The hypotensive response to sodium nitroprusside was smaller, but the accompanying mesenteric vasodilatation was greater, in SD than in TG rats. 6 The contribution of NO to the vasodilator responses was taken as the difference between the responses in the presence of the NO synthase inhibitor, N-G-nitro-L-arginine methylester (L-NAME), compared to those in the presence of a co-infusion of angiotensin II and vasopressin (to match the haemodynamic effects of L-NAME). 7 In TG rats, L-NAME caused a greater absolute presser effect, but a smaller mesenteric vasoconstriction, than in SD rats. 8 L-NAME affected the vasodilator responses to all the challenges similarly in the two strains. 9 Collectively, the results provide no direct evidence for impaired NO-mediated vasodilator mechanisms in TG rats. It is feasible that the reduced hindquarters response to bradykinin and the reduced renal and hindquarters responses to salbutamol, in TG rats are due to abnormal beta(2)- adrenoceptor-mediated processes.