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 the antihypertensive effects of renin-angiotensin system (RAS) inhibition. We examined the effects of the NO synthase inhibitor L-NNA on the hypotensive effects of captopril, the Ang II antagonist EXP 3174, or the 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 partially 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 partially 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 rat, NO in GPs appears to participate only in the hypotensive action of ACE inhibition and does not appear to be strongly involved in the hypotensive action of AII antagonism or renin inhibition. The involvement of NO in the hypotensive effects of RAS antagonists other than ACE inhibitors may be species-dependent.
Mangiapane
M L
ML
Department of Cardiovascular and Metabolic Diseases, Pfizer Central Research, Groton, Connecticut 06340, USA.
Peters
B R
BR
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000172:deficiency*; D013777:Tetrazoles / Q000494:pharmacology; D000092502:Renin Inhibitors
D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D004151:Dipeptides; D007093:Imidazoles; D019808:Losartan; D009025:Morpholines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D012964:Sodium; D013777:Tetrazoles; D000092502:Renin Inhibitors; C076964:terlakiren; C066026:losartan carboxylic acid