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Low-dose ACE with alpha- or beta-adrenergic receptor inhibitors have beneficial SHR cardiovascular effects
J Varagic1, D Susic, E D Frohlich
1Hypertension Research Laboratory, Alton Ochsner Medical Foundation, New Orleans, LA 70121, USA.
Insights
Alpha-1 adrenergic receptor antagonists like doxazosin, combined with low-dose ACE inhibitors, offer cardiovascular benefits in spontaneously hypertensive rats (SHR). This combination effectively reduces cardiac mass and collagen, improving hemodynamics without significant hypotension.
Area of Science:
- Cardiovascular Pharmacology
- Hypertension Research
- Adrenergic Receptor Antagonism
Background:
- Limited data exist on long-term alpha-1 adrenergic receptor antagonist effects on ventricular collagen and coronary hemodynamics in spontaneously hypertensive rats (SHR).
- This study investigated the impact of chronic doxazosin treatment on SHR hemodynamics, cardiovascular mass, and collagen content.
Purpose of the Study:
- To evaluate the effects of doxazosin, alone and in combination with a low-dose ACE inhibitor, on SHR cardiovascular parameters.
- To compare these effects with those of a beta-1 adrenergic receptor inhibitor.
Main Methods:
- Systemic and regional hemodynamics were assessed using radionuclide-labeled microspheres.
- Left and right ventricular weight, hydroxyproline concentration (collagen marker), and aortic weight were measured.
- Treatments included doxazosin, metoprolol, enalapril (low-dose ACE inhibitor), and combinations thereof.
Main Results:
- Doxazosin reduced blood pressure and peripheral resistance but did not alter left ventricular mass or collagen.
- Monotherapies with metoprolol or low-dose enalapril reduced left ventricular mass and collagen without affecting pressure.
- Combination therapy of doxazosin with low-dose enalapril reduced cardiac mass and collagen without potentiating hypotension; aortic weight index decreased with doxazosin alone or combined.
- Both combination therapies and doxazosin alone decreased renal vascular resistance.
Conclusions:
- Low-dose ACE inhibitors combined with alpha- or beta-adrenergic receptor antagonists yield beneficial cardiovascular effects in SHR.
- This combination therapy demonstrates potential for managing hypertension-related cardiac remodeling.
Background:
There are no data regarding the prolonged effect of alpha-1 adrenergic receptor antagonists on ventricular collagen content and coronary hemodynamics in spontaneously hypertensive rats (SHR). This study, therefore, was designed to determine the effects of chronic treatment with the alpha-1 adrenergic receptor inhibitor doxazosin on SHR systemic and regional (especially coronary) hemodynamics, cardiovascular mass, and ventricular collagen. The effects of the combination of doxazosin with low-dose angiotensin-converting enzyme inhibitor were studied versus the alpha-1 antagonist alone. These effects were compared with those of a beta-1 adrenergic receptor inhibitor.
Methods And Results:
Systemic and regional hemodynamics (radionuclide-labeled microspheres), left and right ventricular weight, hydroxyproline concentration, and aortic weight were measured at age 35 weeks. Doxazosin reduced arterial pressure and total peripheral resistance without changing left ventricular mass and collagen content, whereas monotherapies with the beta-1 antagonist metoprolol or a subdepressor dose of the ACE inhibitor enalapril were effective in reducing left ventricular mass and hydroxyproline without altering pressure. Doxazosin combined with the same low-dose ACE inhibitor reduced left ventricular mass and hydroxyproline without potentiating the hypotensive effect of doxazosin. By contrast, the combination of beta-1 antagonist with the low-dose ACE inhibitor reduced pressure, unlike either agent alone. Aortic weight index was significantly reduced only by doxazosin whether when used alone or with the ACE inhibitor. Low-dose ACE inhibitor with doxazosin or the beta-1 receptor antagonist as well as doxazosin alone decreased renal vascular resistance.
Conclusion:
These data show that the low subdepressor dose ACE inhibitor with an alpha- or beta-adrenergic receptor antagonist provides beneficial cardiovascular effects in SHR.
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