Reguratory mechanism of hypotensive responses to muscarinic cholinergic stimulation through the adrenergic receptor system.

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The following findings were obtained in pentobarbital (30mg/kg, i.v) -anesthetized dogs.1.Phenylephrine (Phe) infusions into the right cephalic vein at a rate between 0.3 and 10mug/kg induced persistent and dose-dependent pressor responses through stimulation of alpha-adrenoceptors on the vascular smooth muscle cells.2.Infusions of Phe at a rate in the above range suppressed ACh-induced hypotension in a manner that is dependent on the dose and the period of time of Phe infusion.After Phe infusion at a rate of 3 mug/kg for 120 min shifted the dose-response curve for the hypotensive responses to ACh to the right by about 80-times.3.Inhibitory effect of Phe infusions on the ACh-induced hypotension was long-lasting.For instance, no recovery in the inhibition was observed for at last 120 min after cessation of a Phe infusion that was carried out at a rate of 3 mug/kg for 120 min.Blood pressure returned to the basal level immediately after stopping the Phe infusions.4.Other alpha-adrenoceptor agonists, methoxamine and norepinephrice, and a non-adrenerigic vasoconstrictor, angiotensin II,also inhibited ACh-induced hypotension in a similar manner as observed with Phe, suggesting importance of elevation of blood pressure in this phenomenon.5.Phe infusions little affected hypotensive responses to histamine, sodium nitroprusside, carbachol and methacholine.6.The inhibitory effect of Phe infusions on ACh-induced hypotension was reversed by treatment of dogs with a cholinesterase inhibitor, neostigmine.In addition, only small inhibition was observed when ACh was administered into the left ventricle, instead of vein, even after Phe infusions at a rate of 3 mug/kg for 120min.These results suggest that acceleration of ACh metabolism in the lung is responsible for Phe-induced inhibition of ACh responses.In other animal species examined so far, including rats, guinea-pigs and rabbits, Phe infusions failed to affect hypotensive responses to ACh.