Quinapril prevents hypertension and enhanced vascular reactivity in nitroarginine-treated rats.
Long-term inhibition of nitric oxide synthase (NOS) by substituted arginine analogues has previously been shown to induce systemic hypertension in several animal species; however, the precise mechanisms for the elevated blood pressure remain unclear. We hypothesized that a portion of the hypertensive response to arginine analogues was due to direct inhibition of endothelial NOS and resultant functional alterations in the vasculature that contribute to elevated systemic resistance. Adult Sprague-Dawley rats were treated for 2 weeks with an arginine analogue, N omega Nitro-L-arginine (L-NNA), alone or in combination with the angiotensin converting enzyme (ACE) inhibitor quinapril. Next, thoracic aortas were removed, cut into rings and suspended in isolated tissue baths for measurement of contractile force in response to vasoactive drugs. Our results showed that oral L-NNA treatment significantly elevated systolic blood pressure in rats that was completely prevented by quinapril. Furthermore, L-NNA treatment increased endothelium-dependent and -independent contractility and attenuated endothelium-dependent vasodilation in the thoracic aorta. These functional alterations were also attenuated by quinapril treatment. Therefore, long-term L-NNA-induced hypertension in rats is associated with enhanced vascular reactivity due both to direct inhibition of endothelial NOS and to stimulation of the renin-angiotensin system.
Charpie
J R
JR
Department of Pediatrics, University of Michigan Medical School, Ann Arbor, USA.
Charpie
P M
PM
Goud
C
C
Pitt
B
B
Webb
R C
RC
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000517:prevention & control*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D019335:Nitroarginine / Q000494:pharmacology*; D000077583:Quinapril; D051381:Rats; D017207:Rats, Sprague-Dawley; D044005:Tetrahydroisoquinolines; D014666:Vasomotor System / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D019335:Nitroarginine; D000077583:Quinapril