Mechanisms of reflex vasodilation: assessment of the role of neural reuptake of norepinephrine and release of histamine.
The mechanisms of reflex vasodilation were studied in an innervated canine hindlimb preparation which was perfused at a constant rate. Reflex vasodilation was produced by suddenly increasing the pressure in the trunk by the intravenous injection of norepinephrine, with consequent stimulation of the baroreceptors. When the basal vasoconstrictor tone exerted by the sympathetic nervous system on the systemic arterial bed was minimized, either by pretreatment with the alpha adrenergic blocking agent phenoxybenzamine or with reserpine, which depletes endogenous catecholamine stores, reflex vasodilation was virtually abolished. Administration of cocaine, a drug which blocks reuptake of norepinephrine by the nerve terminals, significantly reduced reflex vasodilation, the response after cocaine averaging 47% of the vasodilator response in the control period. Cocaine also potentiated the vasoconstriction caused by intra-arterially administered norepinephrine but attenuated the vasoconstriction induced by tyramine. The antihistamine, tripelennamine, had effects similar to those of cocaine. It is suggested, therefore, that reflex vasodilation results from a sudden decrease in the level of norepinephrine at the neuroeffector junction, which is a consequence of the cessation of norepinephrine secretion, together with continued and possibly augmented uptake. When the uptake mechanism is impaired, either by the administration of cocaine or tripelennamine, the magnitude of reflex vasodilation is diminished. It does not appear necessary to postulate active secretion of a vasodilator substance to account for reflex vasodilation.
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004285:Dogs; D006614:Hindlimb / Q000294:innervation; D006636:Histamine Release; D009411:Nerve Endings / Q000378:metabolism*; D009451:Neuroeffector Junction / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D012018:Reflex / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013268:Stimulation, Chemical; D014309:Tripelennamine / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010643:Phenoxybenzamine; D014309:Tripelennamine; D012110:Reserpine; D003042:Cocaine; D009638:Norepinephrine; D014439:Tyramine