Modulation of adrenergic receptors during regression of cardiac hypertrophy.
OBJECTIVE
To determine whether alpha 1- or beta-adrenergic receptors are altered during regression of cardiac hypertrophy produced by antihypertensive agents.


METHODS
Cardiac hypertrophy was induced in rats by aortic banding. After 6 weeks banding the rats were treated with an angiotensin converting enzyme (ACE) inhibitor (enalapril), an alpha 1-adrenergic antagonist (bunazosin) or a beta-adrenergic antagonist (propranolol) for 6 weeks to induce regression. The numbers of alpha 1- and beta-adrenergic receptors, haemodynamics, tissue noradrenaline content and tissue ACE activity were measured.


RESULTS
Regression of cardiac hypertrophy occurred after treatment of aortic banded rats with a high dose of enalapril, bunazosin or propranolol, and was accompanied by a reduction in systolic blood pressure. The number of alpha 1- or beta-adrenergic receptors was unchanged by propranolol treatment, but the number of alpha 1-adrenergic receptors was increased in the hearts of rats treated with bunazosin. A low dose of enalapril (3 mg/kg body weight) caused regression of hypertrophy without a concomitant reduction in blood pressure, and decreased the number of alpha 1-adrenergic receptors. The dissociation constants for alpha 1- and beta-adrenergic receptors were not different among the experimental groups, and the positive derivatives of left ventricular pressure was unaltered in rats treated with a low dose of enalapril but was reduced by the other drugs.


CONCLUSIONS
Of the three drugs tested, only the low dose of enalapril affected adrenergic receptors during regression of cardiac hypertrophy, causing a decrease in alpha 1-adrenergic receptor number without a reduction in blood pressure. This effect may be explained by non-haemodynamic actions of the ACE inhibitor enalapril, probably by modulation of peripheral sympathetic activity.
Matsui
H
H
Department of Bioclimatology and Medicine, Kyushu University, Beppu, Japan.
Makino
N
N
Yano
K
K
Nakanishi
H
H
Hata
T
T
Yanaga
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism*; D020120:Iodocyanopindolol; D008297:Male; D009638:Norepinephrine / Q000032:analysis; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000032:analysis* / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D009638:Norepinephrine; D011224:Prazosin