H. Wahlander et al., THERAPEUTIC, BUT NOT LOW-DOSE, ANGIOTENSIN-CONVERTING ENZYME-INHIBITION CAUSES REGRESSION OF CARDIOVASCULAR CHANGES IN SPONTANEOUSLY HYPERTENSIVE RATS, Journal of cardiovascular pharmacology, 27(3), 1996, pp. 327-334
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.