Role of beta 2-adrenoceptor blockade and circulating adrenaline level for the pressor responses to beta-adrenoceptor blocking drugs in rats.
The present experiments were designed to elucidate what mechanism(s) would be responsible for beta-adrenoceptor blocking drugs (beta-blockers)-induced pressor responses in rats. In urethane-anaesthetized rats, 6 beta-blockers at i.v. doses ranging from 0.3 to 300 micrograms/kg evoked the pressor response in a dose-dependent manner. The relative potency in causing the pressor action was correlated not to their beta 1-blocking activities (r = 0.374, P greater than 0.05) but to their beta 2-blocking ones (r = 0.856, P less than 0.05). In pithed or adrenalectomized rats with low levels of plasma catecholamines, however, propranolol failed to exert its sustained pressor action. Propranolol (300 micrograms/kg i.v.) distinctly potentiated the pressor responses not to noradrenaline but to adrenaline and to electrical stimulation of the sympathetic outflow (E.S.) in pithed rats. On the contrary, there was not any potentiation of pressor response to E.S. in pithed, adrenalectomized rats treated with propranolol (300 micrograms/kg i.v.). In rats treated with phenoxybenzamine (5 mg/kg i.v.), adrenaline was shown to have much more potent vasodilating action resulting from beta 2-stimulation than noradrenaline, the dose difference for causing the diastolic blood pressure decrease by a 25 mm Hg being almost 80 times. In pithed rats, infusion of adrenaline at the rate of 0.02 micrograms/min caused a significant increase in plasma adrenaline level from 0.02 +/- 0.01 to 0.45 +/- 0.048 ng/ml, being close to basal level obtained in urethane-anaesthetized rats. Under this situation, propranolol (1-100 micrograms/kg i.v.) showed a distinct pressor response in a dose-dependent fashion as observed in adrenal intact rats anaesthetized with urethane.(ABSTRACT TRUNCATED AT 250 WORDS)
D000315:Adrenalectomy; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003655:Decerebrate State; D004558:Electric Stimulation; D004837:Epinephrine / Q000097:blood* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine