Long-term alpha 1 blockade does not reverse cardiac hypertrophy in spontaneously hypertensive rats.
Not all antihypertensive drugs induce regression of left ventricular (LV) hypertrophy in hypertension, although they may equally lower blood pressure. The effects of alpha 1-blockers on regression have been inconsistent. In this study, bunazosin, a selective alpha 1-blocker, (15 mg/kg/day in food) was given to male spontaneously hypertensive rats (SHR) from 15 to 35 weeks of age to evaluate its effects on cardiac hypertrophy, hemodynamics, and neurohumoral factors. Age- and sex-matched SHR served as controls. LV function and cardiac output were determined by a micromanometer and thermodilution, respectively. Bunazosin significantly decreased blood pressure in conscious rats (from 209 to 192 mmHg, p < 0.01) but did not reduce LV mass. Heart rate, LV end-diastolic pressure, dp/dtmax, and cardiac output were similar in the 2 groups. Plasma renin activity was unaltered but plasma norepinephrine levels were higher in the treated rats (p < 0.05). Thus, bunazosin produced a significant relative reduction of blood pressure but did not reverse LV hypertrophy in SHR. Inadequate afterload reduction (8%) due to severe hypertension (> 200 mmHg) may explain the absence of regression. The rise of plasma norepinephrine levels may also offset the beneficial effects of bunazosin.
Nishimura
H
H
Third Department of Internal Medicine, Osaka Medical College, Japan.
Kubota
J
J
Okabe
M
M
Ueyama
M
M
Oka
T
T
Kawamura
K
K
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000150:complications*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011799:Quinazolines / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood
D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; C018176:bunazosin; D012083:Renin; D009638:Norepinephrine