Long-term alpha 1 blockade does not reverse cardiac hypertrophy in spontaneously hypertensive rats
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H Nishimura1, J Kubota, M Okabe
1Third Department of Internal Medicine, Osaka Medical College, Japan.
Insights
Selective alpha 1-blocker bunazosin lowered blood pressure in hypertensive rats but did not reverse left ventricular hypertrophy. Inadequate afterload reduction and increased norepinephrine may explain these findings.
Area of Science:
- Cardiology
- Pharmacology
- Hypertension Research
Background:
- Antihypertensive drugs vary in their ability to reverse left ventricular (LV) hypertrophy.
- The impact of alpha 1-blockers on cardiac hypertrophy regression remains inconsistent.
Purpose of the Study:
- To investigate the effects of bunazosin, a selective alpha 1-blocker, on cardiac hypertrophy, hemodynamics, and neurohumoral factors in spontaneously hypertensive rats (SHR).
Main Methods:
- Male SHR were treated with bunazosin (15 mg/kg/day) from 15 to 35 weeks of age.
- Hemodynamics were assessed using a micromanometer and thermodilution.
- Plasma renin activity and norepinephrine levels were measured.
Main Results:
- Bunazosin significantly reduced systolic blood pressure (209 to 192 mmHg) but did not decrease LV mass.
- Heart rate, LV end-diastolic pressure, and cardiac output remained unchanged.
- Plasma norepinephrine levels increased in bunazosin-treated rats.
Conclusions:
- Bunazosin achieved a relative reduction in blood pressure but failed to reverse LV hypertrophy in SHR.
- Severe hypertension and potential counter-regulatory norepinephrine increases may limit regression.
Abstract:
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.