ACUTE NICOTINE PRETREATMENT AUGMENTS DOPAMINERGIC PULMONARY VASODILATION

Nicotine use has been associated with augmented dopaminergic neurotran smission within the central nervous system by a number of researchers, We wished to determine if acute nicotine treatment would augment the pulmonary vasodilatory response to dopamine. Male Sprague-Dawley rats were pretreated with either subcutaneous nicotine or equivolume saline and a dose-response curve for dopaminergic pulmonary vasodilation was constructed ex vivo in isolated, salt-perfused rat lungs preconstrict ed with the synthetic thromboxane analogue U-46619, Nicotine pretreatm ent augmented the vasodilatory response to dopamine at doses falling w ithin the mid range of the dopamine dose-response relationship, and th is augmentation was blocked by the nicotinic ganglionic receptor antag onist mecamylamine, In contrast, nicotine did not augment the vasodila tory response produced by either the preferential DA(1)-dopaminergic r eceptor agonist SKF-38393 or the preferential DA(2)-dopaminergic recep tor agonist quinpirole. Acute nicotine pretreatment did not affect the maximal pulmonary vasodilatory response produced by dopamine. Similar ly, nicotine pretreatment failed to augment the vasodilatory response to the beta-adrenergic receptor agonists isoproterenol or terbutaline, but significantly diminished the response to dobutamine. Even though acute nicotine pretreatment did not augment beta-adrenergic receptor-m ediated pulmonary vasodilation, the augmentation of dopaminergic respo nsiveness was inhibited by prior treatment with propranolol, suggestin g beta-adrenergic receptor involvement, Finally, nicotine pretreatment did not alter the vasodilation produced by the nitric oxide dependent agents arginine vasopressin or sodium nitroprusside, These data demon strate that nicotine alters dopaminergic vasodilation in the pulmonary vascular bed.