EFFECTS OF RAMIPRIL ON CONTRACTILE OSCILLATIONS IN ARTERIES FROM GENETICALLY HYPERTENSIVE RATS

We have tested the hypothesis that altered vascular reactivity, specif ically the appearance of spontaneous and BayK 8644 (L-type voltage gat ed calcium channel agonist)-induced oscillations in the carotid artery and the sarcoplasmic reticulum Ca2+-ATPase inhibitor cyclopiazonic ac id (CPA)-induced oscillations in the aorta from stroke-prone spontaneo usly hypertensive rats (SHRSP), are dependent upon angiotensin II prod uction early in life. SHRSP and normotensive Wistar-Kyoto (WKY) rats w ere treated from 6-10 weeks of age with vehicle, hydralazine/hydrochlo rothiazide (used as a control for lowered blood pressure) or the angio tensin converting enzyme inhibitor ramipril (3 mg/kg/day). Systolic bl ood pressures were measured weekly in rats from 6 to 17 weeks of age. In SHRSP (at 17 weeks of age), ramipril-treatment but not hydralazine/ hydrochlorothiazide attenuated the long term expression of elevated sy stolic blood pressure in adult SHRSP while blood pressures of all adul t WKY rats were unaffected by any treatment. At 17 weeks, rats were ki lled and arteries removed for in vitro measurement of isometric contra ctile activity. Only the incidence of spontaneous oscillations (caroti d artery) was affected by ramipril treatment; ramipril did not change the frequency of BayK 8644-induced oscillations in the artery or the f requency of CPA-induced oscillations in aorta from either SHRSP or WKY . These data indicate that while spontaneous oscillations in the carot id artery may be dependent on an angiotensin II-sensitive mechanism du ring development, agonist-induced oscillations (CPA and BayK 8644) app ear not to be angiotensin II-dependent. Thus, not all of the contracti le oscillations which appear in vascular smooth muscle from SHRSP are angiotensin II-dependent, suggesting that some of these vascular abnor malities may develop at a time separate from that in which increased b lood pressure is firmly established and may not be associated with the for maintenance of elevated blood pressure.