ROLE OF NITRIC-OXIDE IN RESPONSES TO RENIN-ANGIOTENSIN SYSTEM INHIBITION IN SODIUM-DEPLETED GUINEA-PIG AND RAT

Previous reports have suggested that NO is an important mediator of th e antihypertensive effects of renin-angiotensin system (RAS) inhibitio n. We examined the effects of the NO synthase inhibitor L-NNA on the h ypotensive effects of captopril, the Ang II antagonist EXP 3174, or th e renin inhibitor terlakiren. In sodium-depleted guinea pigs (GPs), L- NNA (3 mg/kg) increased MAP by 15-21% for at least 5 hours. L-NNA part ially blocked the hypotensive effects of captopril (1 mg/kg, iv), but not those of EXP 3174 (1 mg/kg, iv) or terlakiren (3 mg/kg). In sodium -depleted rats, 10 mg/kg L-NNA (iv) increased MAP by 16-22%, and parti ally or fully blocked the hypotensive effect of EXP 3174 (1 mg/kg, iv) or captopril (3 mg/kg, iv), respectively. Thus, in contrast to the ra t, NO in GPs appears to participate only in the hypotensive action of ACE inhibition and does not appear to be strongly involved in the hypo tensive action of AII antagonism or renin inhibition. The involvement of NO in the hypotensive effects of RAS antagonists other than ACE inh ibitors may be species-dependent.