Low-dose ACE with alpha- or beta-adrenergic receptor inhibitors have beneficial SHR cardiovascular effects.
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.


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.


CONCLUSIONS
These data show that the low subdepressor dose ACE inhibitor with an alpha- or beta-adrenergic receptor antagonist provides beneficial cardiovascular effects in SHR.
Varagic
J
J
Hypertension Research Laboratory, Alton Ochsner Medical Foundation, New Orleans, LA 70121, USA.
Susic
D
D
Frohlich
E D
ED
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003094:Collagen / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D017292:Doxazosin / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005355:Fibrosis; D006352:Heart Ventricles / Q000473:pathology; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000517:prevention & control; D007668:Kidney / Q000098:blood supply; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D014655:Vascular Resistance
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D003094:Collagen; D017292:Doxazosin