Acute infusion of nicotine potentiates norepinephrine-induced vasoconstriction in the hamster cheek pouch.

Although cigarette smoking and the components of cigarette smoke appear to alter nitric oxide synthase-dependent dilation of blood vessels, the effect of these substances on constrictor responses of resistance arterioles has not been examined. Thus the goal of this study was to examine the effect of a major component of cigarette smoke-that is, nicotine-on constrictor responses of cheek pouch arterioles. The diameter of cheek pouch arterioles (approximately 50 microm in diameter) was measured by using intravital microscopy. We examined the responses of arterioles to angiotensin II, arginine vasopressin, norepinephrine, and the thromboxane analog U-46619 before and after treatment with vehicle (saline solution), N(G)-monomethyl-L-arginine (L-NMMA; 1.0 micromol/L), or nicotine (2.0 microg/kg/min i.v. for 30 minutes followed by a maintenance dose of 0.35 microg/kg/min for 30 minutes). Topical application of angiotensin II (0.01 and 0.1 nmol/L), arginine vasopressin (1.0 and 10 pmol/L), norepinephrine (1.0 and 10 nmol/L), and U-46619 (0.01 and 0.1 nmol/L) produced marked reproducible constriction of cheek pouch arterioles in hamsters treated with vehicle. Topical application of L-NMMA potentiated constrictor responses of arterioles to the high dose of arginine vasopressin (28%+/-4% versus 36%+/-4%; P<.05) and to both doses of norepinephrine (14%+/-1% and 24%+/-2% versus 19%+/-1% and 31%+/-3%; P<.05). The infusion of nicotine did not alter responses to angiotensin II, arginine vasopressin, or U-46619 but modestly potentiated vasoconstriction in response to norepinephrine (12%+/-2% and 22%+/-2% versus 14%+/-2% and 26%+/-2%; P<.05). These findings suggest that the synthesis/release of nitric oxide may modulate constrictor responses of cheek pouch resistance arterioles to selected agonists. In addition, nicotine, at levels observed in smokers, may potentiate norepinephrine-induced vasoconstriction. We suggest that preservation/potentiation of vasoconstrictor responses may contribute to the pathogenesis of vascular abnormalities associated with cigarette smoking.