Acute nicotine pretreatment augments dopaminergic pulmonary vasodilation

Nicotine use has been associated with augmented dopaminergic neurotransmission 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 preconstricted with the synthetic thromboxane analogue U-46619. Nicotine pretreatment augmented the vasodilatory response to dopamine at doses falling within the mid range of the dopamine dose-response relationship, and this augmentation was blocked by the nicotinic ganglionic receptor antagonist mecamylamine. In contrast, nicotine did not augment the vasodilatory response produced by either the preferential DA1-dopaminergic receptor agonist SKF-38393 or the preferential DA2-dopaminergic receptor agonist quinpirole. Acute nicotine pretreatment did not affect the maximal pulmonary vasodilatory response produced by dopamine. Similarly, 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-mediated pulmonary vasodilation, the augmentation of dopaminergic responsiveness was inhibited by prior treatment with propranolol, suggesting 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 demonstrate that nicotine alters dopaminergic vasodilation in the pulmonary vascular bed.