Effects of beta-antagonists and beta 1-partial agonists on the pulmonary pressor response to 5-HT

Abstract

The effects of beta-antagonists (propranolol, pindolol, atenolol) and beta 1-partial agonists (xamoterol, denopamine) on the pulmonary circulation, and on the pressor response to 5-HT were investigated and compared with those of a beta-agonist, isoproterenol. These agents (at doses of 0.002-20 mg) were administrated into the isolated lung lobe perfusion system excised from mongrel dogs (7-12 kg in weight). Under standard conditions (mean pulmonary inflow pressure, 15 mmHg; mean outflow pressure, 5 mmHg), propranolol and atenolol had no effect on pulmonary vascular resistance (PVR) at the tested doses, but pindolol which has intrinsic sympathomimetic activity (ISA) and two beta 1-partial agonists significantly decreased PVR in a dose-dependent manner (each n = 7). Isoproterenol, up to a dose of 0.2 mg, markedly decreased PVR, but induced vasoconstriction in larger doses (n = 7). Propranolol and xamoterol similarly reduced the pressor response to 30 micrograms of 5-HT from a dose of 2 mg, and these inhibitory actions were greater than those of the other drugs. Pindolol and denopamine inhibited the 5-HT response in a dose of 20 mg, whereas atenolol only augmented the response in a dose-dependent manner. In conclusion, beta-antagonists with ISA (including beta 1-partial agonist activity) can dilate the pulmonary vessels in a dose-dependent manner, but not beta-antagonists without ISA. Furthermore, the 5-HT inhibitory effects caused by relatively large doses of beta-antagonists, except for atenolol, may be related to the 5-HT receptor blockade or other unknown mechanisms, including calcium influx or prostaglandin synthesis, but not to the beta-receptor blockade.