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

We have tested the hypothesis that altered vascular reactivity, specifically the appearance of spontaneous and BayK 8644 (L-type voltage gated calcium channel agonist)-induced oscillations in the carotid artery and the sarcoplasmic reticulum Ca2+-ATPase inhibitor cyclopiazonic acid (CPA)-induced oscillations in the aorta from stroke-prone spontaneously hypertensive rats (SHRSP), are dependent upon angiotensin II production early in life. SHRSP and normotensive Wistar-Kyoto (WKY) rats were treated from 6-10 weeks of age with vehicle, hydralazine/hydrochlorothiazide (used as a control for lowered blood pressure) or the angiotensin converting enzyme inhibitor ramipril (3 mg/kg/day). Systolic blood 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 systolic blood pressure in adult SHRSP while blood pressures of all adult WKY rats were unaffected by any treatment. At 17 weeks, rats were killed and arteries removed for in vitro measurement of isometric contractile activity. Only the incidence of spontaneous oscillations (carotid artery) was affected by ramipril treatment; ramipril did not change the frequency of BayK 8644-induced oscillations in the artery or the frequency of CPA-induced oscillations in aorta from either SHRSP or WKY. These data indicate that while spontaneous oscillations in the carotid artery may be dependent on an angiotensin II-sensitive mechanism during development, agonist-induced oscillations (CPA and BayK 8644) appear not to be angiotensin II-dependent. Thus, not all of the contractile oscillations which appear in vascular smooth muscle from SHRSP are angiotensin II-dependent, suggesting that some of these vascular abnormalities may develop at a time separate from that in which increased blood pressure is firmly established and may not be associated with the for maintenance of elevated blood pressure.