Effects of trandolapril on vascular morphology and function during the established phase of systemic hypertension in the spontaneously hypertensive rat.
The aim of this study was to determine the morphologic and functional vascular changes occurring following 4 weeks of treatment with the angiotensin-converting enzyme inhibitor trandolapril in the spontaneously hypertensive rat (SHR) in the established phase of hypertension. At the dosage used, 0.4 mg/kg orally, trandolapril decreased blood pressure of the SHR by 15-18% compared with that of the control animals. Immediately before the end of treatment, the following changes from control values were observed: (1) 9, 11, and 12% reductions for myocardial hypertrophy and the media thickness of the thoracic aorta and femoral arteries, respectively; and (2) an increase in the compliance of the resistance arteries, demonstrated by a shift to the right of the in vitro tension-diameter curves and a significant 22% increase in their normalized internal diameter, while their maximum contractile ability was significantly decreased. Following discontinuation of treatment, blood pressure levels remained significantly lower in the treated versus the control groups for up to 4 weeks after the last administration. At that time measurement of the studied parameters showed: (1) a rapid reversion to control values of the compliance of the resistance vessels; and (2) a slower progression, but in the same direction, in the parameters of cardiac and vascular hypertrophy. Thus, trandolapril, administered for a short period in the adult SHR, was able to reverse the cardiac and vascular morphologic changes present in this model of hypertension. Like the effect on blood pressure, these effects were slowly reversible at the end of treatment, whereas the functional consequences at the resistance artery level seemed to display a more rapid reversibility.
Freslon
J L
JL
Département de Pharmacodynamie, Université de Bordeaux II, France.
Pourageaud
F
F
Lecaque
D
D
Secchi
J
J
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006332:Cardiomegaly / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006984:Hypertrophy / Q000188:drug therapy; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril