THERAPEUTIC, BUT NOT LOW-DOSE, ANGIOTENSIN-CONVERTING ENZYME-INHIBITION CAUSES REGRESSION OF CARDIOVASCULAR CHANGES IN SPONTANEOUSLY HYPERTENSIVE RATS

Therapy with angiotensin II-converting enzyme (ACE) inhibitors has bee n suggested to prevent cardiovascular hypertrophy in hypertension even in doses that are subantihypertensive. We investigated the effects of two different ACE inhibitors on blood pressure and cardiovascular cha nges during as well as after discontinuation of treatment in spontaneo usly hypertensive rats (SHR). SHR were treated with either enalapril ( ENA) or ramipril (RAM) from age 12 to age 20 weeks. Each drug was give n in either an antihypertensive (ENA 15 mg . kg(-1), RAM 3 mg . kg(-1) ) or a subantihypertensive (ENA 50 mu g . kg(-1), RAM 10 mu g . kg(-1) ) dose. Mean arterial pressure (MAP) was reduced with antihypertensive doses of ENA (26%) as well as RAM (21%). Regression of cardiovascular changes occurred as reduction in left ventricular (LV) weight/body we ight ratio (25 and 21% for ENA and RAM, respectively), reduction in pe rfusion pressure at maximal vasodilation of the perfused hindquarter ( PPdil, 17 and 17%), and reduction in maximal developed pressure (PPmax , 13 and 17%). These effects partly persisted IO weeks after treatment was discontinued. However, treatment with subantihypertensive doses o f ENA and RAM had no effect on MAP, LV/body weight ratio, PPdil, or PP max. Overall, regression of cardiovascular parameters correlated close ly to the decrease in MAP. Similarly, no changes in MAP, LV weight/bod y weight ratio, PPdil, or PPmax were noted when young SHR were treated with subantihypertensive doses of RAM from age 6 to age 12 weeks, dur ing which time hypertension becomes established. At doses having equal effects on blood pressure, plasma concentrations of RAM were consider ably lower than those of ENA. Skeletal muscle concentrations were very low or undetectable in comparison to plasma concentrations for both d rugs. Therefore, both RAM and ENA caused regression of cardiovascular changes that could be explained by a concomitant reduction in blood pr essure. This regression persisted for a considerable time after discon tinuation of treatment. On the other hand, no specific antitrophic eff ects in the absence of blood pressure reduction was evident with eithe r drug. Furthermore, despite substantial differences in plasma concent rations, RAM, and ENA administered chronically appeared to affect card iovascular parameters equally in the adult SHR.