Effects of chronic administration of bopindolol on the binding characteristics of cardiac alpha 1H-, alpha 1L-, beta 1- and beta 2-adrenoceptor subtypes in cardiac muscles of spontaneously hypertensive rats (SHR).
The effects of the chronic administration of bopindolol on the binding characteristics of [3H]CGP12177 and [3H]prazosin to cardiac alpha 1H-, alpha 1L-, beta 1- and beta 2-adrenoceptor subtypes of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were compared with those of two other beta-blockers, atenolol and propranolol. Bopindolol (1 and 3 mg/kg/d), atenolol (50 mg/kg/d) and propranolol (60 mg/kg/d) were given to 10-week-old SHR for 12 weeks. The changes in Kd and Bmax values of the myocardium of SHR treated without and those drugs were assessed by Scatchard analysis, and the ratio and Bmax values of the beta 1- and beta 2-adrenoceptor subtypes were also calculated from displacemental curves using ICI 118,551. The systolic blood pressure in SHR was dose-dependently lowered by the administration of bopindolol, and was also lowered by the administration of atenolol and propranolol. The Bmax values of beta 1- and beta 2-adrenoceptors were lowered by the administration of bopindolol (1 and 3 mg/kg/d) without any changes in the Kd values or the ratio of beta 1- and beta 2-adrenoceptors. Propranolol lowered 3-fold the affinity to the beta-adrenoceptor. On the other hand, the Kd and Bmax values of alpha 1H- and alpha 1L-adrenoceptor subtypes (high and low affinity binding sites for [3H]prazosin) were not changed by these drugs. These findings suggest that bopindolol had a beneficial effect on beta-adrenoceptors in the membranes of cardiac muscles of SHR, implying that these effects may contribute to lowering hypertension.
Hosohata
Y
Y
Department of Pharmacology, Niigata College of Pharmacy, Japan.
Sasaki
K
K
Maruyama
K
K
Ohnuki
T
T
Hattori
K
K
Suzuki
J
J
Watanabe
K
K
Nagatomo
T
T
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011412:Propanolamines / Q000493:pharmacokinetics; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D018340:Receptors, Adrenergic, alpha-1; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D001262:Atenolol; D011433:Propranolol; D010869:Pindolol; C036007:bopindolol; C033394:CGP 12177