Hemodynamic and coronary vasodilative properties of a selective and full beta 1-adrenoceptor agonist, T-0509, in comparison with isoproterenol in anesthesized dogs.
Recently, the beta 1-adrenoceptor was shown to mediate direct coronary vasodilation independent of metabolic demand in canine arrested heart preparation. To investigate the beta 1-adrenoceptor-mediated direct vasodilation in a beating heart preparation, we compared coronary blood flow (CBF) and coronary sinus oxygen tension (PO2) in anesthetized open-chest dogs using a beta 1-selective agonist, T-0509. T-0509 (0.005-0.05 microgram/kg intravenously, i.v.) increased the maximal rate of increase in left ventricular pressure (LVdp/dtmax) and heart rate (HR) to an extent similar to that induced by isoproterenol (ISO) without decreasing diastolic blood pressure (DBP). A beta 1-adrenoceptor antagonist, (-)-bisoprolol (10 micrograms/kg), but not a beta 2-adrenoceptor antagonist, ICI 118,551 (30 micrograms/kg), inhibited the T-0509-induced increase in LVdp/dtmax and HR. Thus, T-0509 showed selective beta 1 stimulation at the doses used. T-0509 also caused beta 1-selective relaxation in isolated coronary arteries. ISO increased both CBF and PO2. The early phase of the increase in CBF and the concurrent increases in PO2 were inhibited by ICI 118,551, whereas the late phase of the increase in CBF was inhibited by (-)-bisoprolol. T-0509 increased CBF, and this increase was inhibited by (-)-bisoprolol. A slight but significant increase in PO2 induced by T-0509 was not altered by these doses of the antagonists. Our results indicate that the T-0509-induced increase in CBF is due mainly to an indirect effect on myocardial beta 1-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Yamazaki
J
J
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Sugimoto
T
T
Yabana
H
H
Nagao
T
T
D058665:Adrenergic beta-1 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D014665:Vasodilator Agents / Q000494:pharmacology*
D058665:Adrenergic beta-1 Receptor Agonists; D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D014665:Vasodilator Agents; C025342:RP333; D007545:Isoproterenol