Biphasic Antagonisms by β-Blockers Against Positive Inotropic Response Through β1-Adrenoceptors in Isolated Canine Right Ventricular Muscles: Possible Involvement of Two β1-Adrenoceptor Subtypes

Hideo Kurosawa, Teruyuki Yanagisawa, Norio Taira

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

In isolated canine right ventricular muscles, we investigated the differences in antagonisms by β-blockers against the positive inotropic effects (PIEs) of isoproterenol, a nonselective agonist, and T-0509, a β1-selective agonist. The selective β1-blockers atenolol and bisoprolol antagonized the PIE of T-0509 monophasically in Schild analysis, showing pA2 values of 7.05 and 7.63, respectively. On the other hand, both blockers produced biphasic antagonism against the PIE of isoproterenol (ISO); therefore, two pKB values were obtained (7.75 and 4.25 and 7.82 and 5.76, respectively). Nadolol, a nonselective β-blocker, also antagonized the PIE of T-0509 monophasically (pA2 value 7.58), but antagonized the PIE of ISO biphasically (pKB values 7.42 and 4.39). Because the different mode of antagonism by three β-blockers between T-0509 and ISO could not be explained by the selectivities of β-agonists and blockers for β1 and β2-adrenoceptors in the heart, two subtypes of β1-adrenoceptors may exist together in canine ventricular muscles, and atenolol, bisoprolol, and nadolol may act as antagonists for the two subtypes with two different affinities.

Original languageEnglish
Pages (from-to)262-268
Number of pages7
JournalJournal of cardiovascular pharmacology
Volume27
Issue number2
DOIs
Publication statusPublished - 1996

Keywords

  • High-affinity β-adrenoceptor
  • Isoproterenol
  • Low-affinity β-adrenoceptor
  • Positive inotropic effect
  • T-0509

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Biphasic Antagonisms by β-Blockers Against Positive Inotropic Response Through β<sub>1</sub>-Adrenoceptors in Isolated Canine Right Ventricular Muscles: Possible Involvement of Two β<sub>1</sub>-Adrenoceptor Subtypes'. Together they form a unique fingerprint.

Cite this