The relative contributions of the hemodynamic and morphological (vascular and cardiac) modifications induced by long-term administration of an
angiotensin I-converting enzyme inhibitor,
quinapril, to the
drug's long-lasting preventive effects vis-à-vis genetic
hypertension development (GHD) have been investigated in young spontaneously hypertensive rats (SHRs). Two groups of SHRs were given
quinapril (10 mg/kg/day) or distilled water from 5 to 20 weeks of age. The
drug was then stopped, but observations continued for another 7 weeks. At selected times systemic and regional hemodynamic parameters as well as cardiac and vascular morphological effects were investigated. During the treatment period,
quinapril partially opposed GHD and limited the early rise in total peripheral and regional vascular resistances observed in control animals.
Quinapril's partial preventive effect vis-à-vis GHD persisted, but faded
after treatment withdrawal. From a morphological point of view,
quinapril strongly opposed aortic wall
hypertrophy as evidenced by significant reductions in media thickness and wall to lumen ratio and by a significant increase in aortic nuclear density.
Quinapril also limited vascular
fibrosis development. At the cardiac level,
quinapril reduced heart weight to
body weight ratio and opposed myocardial
hypertrophy and cardiac
collagen synthesis. All these vascular and cardiac morphological changes were delayed (starting after 9-15 weeks of treatment) as compared to
quinapril's hemodynamic effects. Finally, the
drug's vascular and cardiac antihypertrophic properties persisted
after treatment withdrawal. In conclusion, our data indicate that the early systemic and regional hemodynamic effects of
quinapril initiate its
antihypertensive action, but the
drug-induced delayed and prolonged vascular morphological changes later take over and may be partly responsible for
quinapril's residual blood pressure lowering effects
after treatment withdrawal.