Effect of ramipril on alpha-adrenoceptor-mediated oscillatory contractions in tail artery of hypertensive rats.
Recent studies indicate that norepinephrine-induced contractile oscillations in the tail artery from stroke-prone spontaneously hypertensive rats (SHRSP) may be a vascular phenomenon independent of blood pressure level. The objectives of this study were: (1) to characterize pharmacologically the alpha-adrenoceptor mediating norepinephrine-induced oscillations in tail artery; and (2) to investigate the relationship between blood pressure level, altered by treatments with hydralazine/hydrochlorothiazide or the angiotensin converting enzyme inhibitor ramipril, and the observation of norepinephrine-induced oscillations in tail artery. The alpha 2-adrenoceptor agonists clonidine and guanabenz potently stimulated oscillatory contractions in the tail artery while the alpha 1-adrenoceptor agonists phenylephrine and methoxamine were considerably less potent. Yohimbine, an alpha 2-adrenoceptor antagonist, but not the alpha 1-adrenoceptor antagonist prazosin demonstrated high affinity for the receptor mediating norepinephrine-induced oscillatory contractions. These results support the hypothesis that norepinephrine-induced oscillatory contractions in the tail artery from SHRSP occur primarily through stimulation of alpha 2-adrenoceptors. Ramipril lowered blood pressure in SHRSP after 4 weeks of treatment during 6-10 weeks of life but did not alter the ability of the alpha 2-adrenoceptor agonist clonidine (10(-5) M) to induce contractile oscillations in tail arteries from SHRSP, indicating these oscillations are not a secondary effect of high blood pressure. These studies suggest that norepinephrine-induced oscillations in tail artery from SHRSP may be a vascular trait separate and distinct from blood pressure level and angiotensin II expression early in life.
Watts
S W
SW
Department of Physiology, University of Michigan, Ann Arbor 48109.
Traub
O
O
Lamb
F S
FS
Myers
J H
JH
Webb
R C
RC
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000235:genetics; D004198:Disease Susceptibility; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010507:Periodicity; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013623:Tail / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D017257:Ramipril; D009638:Norepinephrine