Effects of thymoxamine on ouabain-induced arrhythmias in dogs.

Abstract

The effect of thymoxamine, a pure alpha-adrenoceptor blocking agent, on ouabain-induced arrhythmias was investigated in dogs to clarify whether thymoxamine has an arrhythmogenic or an anti-arrhythmic action. Thymoxamine, 1 mg/kg i.v., inhibited the manifestation of ventricular arrhythmias (VA) and the pressor effect produced by ouabain infusion (1,ug/kg/min i.v.) as 5 mg/ kg i.v. of phentolamine did. Low doses of these drugs did not affect the VA. Simultaneous infusion of phenylephrine (5 yg/kg/min i.v.) with ouabain enhanced the manifestation of VA accompanying pressor effects, which were inhibited by thymoxamine (1 mg/kg) in a parallel manner. Infusion of isoprenaline (0.2 µg/ kg/min i.v.) with ouabain enhanced the manifestation of VA, but the enhancement was to a lesser extent than with phenylephrine. Thymoxamine, 1 mg/kg, did not affect the VA. The infusion of CaC12 (20 mg/kg/min i.v.) with ouabain enhanced the manifestation of VA, which was not inhibited by thymoxamine. These results show the possibility that the protective effect of thymoxamine on the manifestation of VA may be mainly associated with inhibitions of pressor effects mediated through vascular alpha-adrenoceptors. alpha blocker; thymoxamine; phentolamine; ouabain-induced arrhythmias It has been generally recognized that many of beta-adrenoceptor blocking agents have anti-arrhythmic actions. Its possible mechanisms would be related to a blocking action on beta-adrenoceptors, an inhibition of postganglionic cardiac sympathetic neural discharges, and a direct depression of cardiac excitability in a manner similar to quindine (Lucchesi 1965;Somani and Lum 1965). On the other hand, many authors observed that alpha-adrenoceptor blocking agents also have anti-arrhythmic properties in man and laboratory animals (Leimdorfer 1952;Morris et al. 1952;Gould et al. 1969). However, its possible mechanism is not clear enough. In the present experiments, the effects of phentolamine and thymoxamine on ouabain-induced arrhythmias were examined and a possible involvement of alpha-adrenoceptors in the heart or peripheral vascular beds in manifestation of ventricular arrhythmias (VA) was discussed.

Theoretical Study of the Human Bradykinin–Bradykinin B2 Receptor Complex

“…[17,18] Bradykinin also plays some role in higher brain functions [19] and has been proposed as a physiological milk ejection stimulant. [20] Computational studies have previously been performed to investigate hormone/ligand-GPCR complex structures at the molecular level. [21,22] Two crystal GPCR structures have been solved: the ground state rhodopsin (Rh) structure [23,24] and the inactive form of the b 2 -adrenergic receptor (b2ADR).…”