Alterations of binding characteristics of alpha 1-,beta 1-adrenoceptors and Ca2+ binding sites in the myocardium of spontaneously hypertensive rats (SHR) by chronically administered bunazosin, atenolol, ketanserin and verapamil.
The effects of chronic treatment with bunazosin, atenolol, ketanserin and verapamil on the myocardium of the spontaneously hypertensive rat (SHR) were examined by the radioligand binding assay method using [3H]prazosin, [125I]iodocyanopindolol and [3H]nitrendipine binding to alpha 1- and beta 1-adrenergic receptors and Ca2+ binding sites. The norepinephrine concentration in the rat myocardium was also determined. (1) All of these drugs lowered the elevated blood pressure of the SHR. (2) Only ketanserin administration increased the Kd value of the alpha 1-adrenoceptor in the SHR. (3) Administration of atenolol and ketanserin to the SHR decreased the Bmax value of the beta 1-adrenoceptor. (4) Verapamil, bunazosin and atenolol also lowered the Bmax values of the Ca2+ binding sites of SHRs. (5) All drugs except for atenolol lowered the norepinephrine concentration in the myocardium of the SHR. These findings suggest that the SHR has an abnormality of the alpha 1- and beta 1-adrenoceptors and Ca2+ binding site of the myocardium, that the drugs had a beneficial effect on these receptors, that the drugs could also lower the high norepinephrine content in the myocardium of the SHR and that some of these drugs also affected the binding characteristics of other types of membrane receptors.
Watanabe
K
K
Division of Cardiovascular Research Lab., Tsubame Rosai Hospital, Niigata, Japan.
Shibata
A
A
Wakabayashi
H
H
Shimada
K
K
Tsuchihashi
H
H
Nagatomo
T
T
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D015220:Calcium Channels; D011799:Quinazolines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D001262:Atenolol; D007650:Ketanserin; C018176:bunazosin; D014700:Verapamil; D009638:Norepinephrine