Impaired acetylcholine-induced cutaneous vasodilation in young smokers: roles of nitric oxide and prostanoids.

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Impaired acetylcholine-induced cutaneous vasodilation in young smokers: roles of nitric oxide and prostanoids.

Am J Physiol Heart Circ Physiol. 2013 Mar 1;304(5):H667-73

Authors: Fujii N, Reinke MC, Brunt VE, Minson CT

Abstract
Cigarette smoking attenuates acetylcholine (ACh)-induced cutaneous vasodilation in humans, but the underlying mechanisms are unknown. We tested the hypothesis that smokers have impaired nitric oxide (NO)- and cyclooxygenase (COX)-dependent cutaneous vasodilation to ACh infusion. Twelve young smokers, who have smoked more than 5.2 � 0.7 yr with an average daily consumption of 11.4 � 1.2 cigarettes, and 12 nonsmokers were tested. Age, body mass index, and resting mean arterial pressure were similar between the groups. Cutaneous vascular conductance (CVC) was evaluated as laser-Doppler flux divided by mean arterial pressure, normalized to maximal CVC (local heating to 43.0�C plus sodium nitroprusside administration). We evaluated the increase in CVC from baseline to peak (CVC?peak) and area under the curve of CVC (CVCAUC) during a bolus infusion (1 min) of 137.5 ?M ACh at four intradermal microdialysis sites: 1) Ringer (control), 2) 10 mM N(G)-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor), 3) 10 mM ketorolac (COX inhibitor), and 4) combination of l-NAME + ketorolac. CVC?peak and CVCAUC at the Ringer site in nonsmokers were greater than in smokers (CVC?peak, 42.9 � 5.1 vs. 22.3 � 3.5%max, P < 0.05; and CVCAUC, 8,085 � 1,055 vs. 3,145 � 539%max�s, P < 0.05). In nonsmokers, CVC?peak and CVCAUC at the l-NAME site were lower than the Ringer site (CVC?peak, 29.5 � 6.2%max, P < 0.05; and CVCAUC, 5,377 � 1,109%max�s, P < 0.05), but in smokers, there were no differences between the Ringer and l-NAME sites (CVC?peak, 16.8 � 4.3%max, P = 0.11; and CVCAUC, 2,679 � 785%max�s, P = 0.30). CVC?peak and CVCAUC were reduced with ketorolac in nonsmokers (CVC?peak, 13.3 � 3.6%max, P < 0.05; and CVCAUC, 1,967 � 527%max�s, P < 0.05) and smokers (CVC?peak, 7.8 � 1.8%max, P < 0.05; and CVCAUC, 1,246 � 305%max�s, P < 0.05) and at the combination site in nonsmokers (CVC?peak, 15.9 � 3.1%max, P < 0.05; and CVCAUC, 2,660 � 512%max�s, P < 0.05) and smokers (CVC?peak, 11.5 � 2.6%max, P < 0.05; and CVCAUC, 1,693 � 409%max�s, P < 0.05), but the magnitudes were greater in nonsmokers (P < 0.05). These results suggest that impaired ACh-induced skin vasodilation in young smokers is related to diminished NO- and COX-dependent vasodilation.

PMID: 23316063 [PubMed - indexed for MEDLINE]

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