[Effects of beta-antagonists and beta 1-partial agonists on the pulmonary pressor response to 5-HT].
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.
Takashio
T
T
First Department of Internal Medicine, Asahikawa Medical College, Hokkaido, Japan.
Yamashita
H
H
Onodera
S
S
Inoue
H
H
Oomiya
H
H
Tanazawa
S
S
Obara
A
A
Imamoto
T
T
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D003864:Depression, Chemical; D004285:Dogs; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply*; D012701:Serotonin / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014655:Vascular Resistance / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D012701:Serotonin