EFFECT OF RAMIPRIL ON ALPHA-ADRENOCEPTOR-MEDIATED OSCILLATORY CONTRACTIONS IN TAIL ARTERY OF HYPERTENSIVE RATS

Recent studies indicate that norepinephrine-induced contractile oscill ations in the tail artery from stroke-prone spontaneously hypertensive rats (SHRSP) may be a vascular phenomenon independent of blood pressu re level. The objectives of this study were: (1) to characterize pharm acologically the alpha-adrenoceptor mediating norepinephrine-induced o scillations in tail artery; and (2) to investigate the relationship be tween blood pressure level, altered by treatments with hydralazine/hyd rochlorothiazide or the angiotensin converting enzyme inhibitor ramipr il, and the observation of norepinephrine-induced oscillations in tail artery. The alpha2-adrenoceptor agonists clonidine and guanabenz pote ntly stimulated oscillatory contractions in the tail artery while the alpha1-adrenoceptor agonists phenylephrine and methoxamine were consid erably less potent. Yohimbine, an alpha2-adrenoceptor antagonist, but not the alpha1-adrenoceptor antagonist prazosin demonstrated high affi nity for the receptor mediating norepinephrine-induced oscillatory con tractions. These results support the hypothesis that norepinephrine-in duced oscillatory contractions in the tail artery from SHRSP occur pri marily through stimulation of alpha2-adrenoceptors. Ramipril lowered b lood pressure in SHRSP after 4 weeks of treatment during 6-10 weeks of life but did not alter the ability of the alpha2-adrenoceptor agonist clonidine (10(-5) M) to induce contractile oscillations in tail arter ies from SHRSP, indicating these oscillations are not a secondary effe ct of high blood pressure. These studies suggest that norepinephrine-i nduced oscillations in tail artery from SHRSP may be a vascular trait separate and distinct from blood pressure level and angiotensin II exp ression early in life.