Effect of subchronic exposure to mainstream cigarette smoke on endothelium-dependent vasodilation in rat arteries
Abstract
Background: Cigarette smoking is reported to impair endothelium-dependent vasodilation. The aim of the present study was to assess the effect of 30-day exposure to mainstream cigarette smoke on vascular reactivity of rat abdominal aorta, carotid, renal and mesenteric artery. Separately, the NO-mediated and the EDHF-mediated, endothelium-dependent vascular relaxations were determined.
Methods: Two groups of »Whistar Kyoto« rats were exposed to mainstream cigarette smoke (2 hours/day, 5 days/week for 30 days) and to fresh conditioned air, respectively. Rats were sacrificed on the second day after the last exposition to cigarette smoke. Vascular reactivity studies were performed on isolated, endothelium-intact, phenylephrine-preconstricted rat artery rings. Cumulative concentration-relaxation curves to acetylcholine (ACh) were obtained in the absence and presence of the endothelial NO synthase (eNOS) inhibitor N ω nitro L-arginine (L-NA) and the cyclo-oxygenase (COX) inhibitor diclofenac, respectively. After washing period of 1 hour, vessels were exposed either to the intracellular superoxide scavenger tiron, to the cytochrome P450 (CYP) inhibitor miconazole or the Na-K-ATPase inhibitor ouabain before being preconstricted with phenylephrine and determining the concentration-response curve to ACh.
Results: ACh induced concentration-dependent relaxations. In none of the vessels investigated did we observe a significant difference in the relaxations obtained in arteries from control rats and rats exposed to cigarettee smoke. Although smoking is known to cause an increase in oxidative stress, treatment of the vessels with tiron did not affect the NOmediated relaxations. To evaluate the contribution of EDHF to endothelium-dependent vasodilation rings were preincubated with L-NA. The EDHF-mediated relaxations were significantly attenuated compared to the NO-mediated relaxations in renal and mesenteric artery and almost completely abolished in aorta and carotid artery in both groups of rats. Comparing the EDHF-mediated relaxations in arterial preparations from the control group with those from smoke-treated rats, we found no significant differences in ACh-induced relaxations. The inclusion of both, miconazole and ouabain in organ chambers induced a rightward shift in the ACh-induced, EDHF-mediated relaxations in renal and mesenteric arteries what confirmed the involvement of CYP and Na/K ATPase in EDHF-mediated relaxations. Again, no differences were registered between the vessels of treated and untreated group.
Conclusions: The results of the present study show that 30 days of transient (subchronic) exposure to cigarette smoke did not induce detectable changes in global endothelial function, or in specific NO and EDHF-mediated relaxations in the rat aorta or in carotid, mesenteric and renal arteries.
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