title: Hemodynamic effects of nicotine in canine skeletal muscle.
abstract: Studies were conducted in 36 artificially ventilated, anesthetized dogs to clarify hemodynamic effects of nicotine in resting gracilis muscle. In Series 1, effects of intravenous nicotine (36 micrograms/kg/min) were evaluated in (i) intact muscles (Condition 1), (ii) denervated muscles (Condition 2), (iii) denervated muscles following local alpha-adrenergic blockade (Condition 3), (iv) denervated muscles following combined local alpha- and beta-adrenergic blockade (Condition 4), and (v) intact muscles with aortic pressure maintained constant (Condition 5). In Series 2, nicotine was infused directly into the gracilis artery at a rate of 3.6 micrograms/kg/min. Muscle blood flow was obtained with an electromagnetic flowmeter and used to calculate vascular resistance and oxygen consumption (Fick equation). Plasma catecholamine levels were determined with a radioenzymatic method. Intravenous nicotine doubled mean aortic pressure under Conditions 1-4. In intact and denervated muscles (Conditions 1 and 2) proportional increases in vascular resistance, reflective of vasoconstriction, held blood flow constant. Muscle oxygen consumption was unchanged. alpha-Adrenergic blockade with phenoxybenzamine following denervation (Condition 3) converted muscle vasoconstriction to vasodilation during nicotine infusion. Additional beta-adrenergic blockade (Condition 4) restored muscle vasoconstriction. Nicotine-induced muscle vasoconstriction was maintained under controlled pressure (Condition 5). Intravenous nicotine significantly increased plasma catecholamine levels. Intra-arterial infusions of nicotine (Series 2) caused no hemodynamic changes in muscle. In conclusion, intravenous nicotine caused vasoconstriction in muscle, which was not due to reduced metabolic demand, pressure-flow autoregulation, or a direct [corrected] effect on vascular smooth muscle, but to stimulation of alpha-adrenergic receptors. Following denervation, this vasoconstriction was maintained by elevated plasma catecholamines. alpha-Adrenergic blockade unmasked nicotine-induced vasodilation mediated by beta-adrenergic receptors, whereas combined alpha- and beta-adrenergic blockade unmasked nicotine-induced vasoconstriction by a nonadrenergic mechanism.
authors.affiliation: Department of Anesthesiology, Illinois Masonic Medical Center, Chicago 60657.
authors.forename: G J
authors.initials: GJ
authors.lastname: Crystal
mesh_terms: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D009132:Muscles / Q000098:blood supply* / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010643:Phenoxybenzamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010643:Phenoxybenzamine; D009538:Nicotine; D011433:Propranolol