Background and purpose
A number of previous studies have shown that both cigarette smoking and smoke extract impair the nitric oxide synthase (NOS)-dependent reactivity of peripheral blood vessels, but not clearly shown in cerebral vessels. It is possible that antagonizing the action of angiotensin II might limit or prevent the endothelial dysfunction induced by free radicals that is associated with cigarette smoking. Our aim is to test whether the response of cerebral arterioles to acetylcholine (Ach; endothelium-dependent vasodilation) is altered (a) after brief inhalation of cigarette smoke or (b) by administration of nicotine itself. In addition, we investigated the effects of an angiotensin II type 1 (AT1)-receptor blocker (valsartan) on the impairment of endothelium-dependent vasodilation in cerebral arterioles induced by acute cigarette smoking.
Materials and methods
In pentobarbital-anesthetized, mechanically ventilated Sprague-Dawley rats (350 g ∼ 400 g), we used a closed cranial window preparation to measure changes in pial vessel diameters. We initially examined the response of arterioles to an endothelium-dependent vasodilator [Ach (10–6 M and 10–5 M)] and also to an endothelium-independent vasodilator [adenosine (10–5 M and 10–4 M)] before smoking (n=6, each). Then, 1 h after smoking had been performed we again examined the responses of arterioles to the larger doses of Ach and adenosine. In experiment 2, we examined the effects of acute infusion of nicotine on the reactivity of cerebral arterioles to Ach(n=6). Then, in experiment 3, after intravenous valsartan pretreatment we reexamined the pial vasodilator response to topical Ach (before and after cigarette smoking; n=6).
Results
Under control conditions, cerebral arterioles were dilated by 6. 9±4.2% and 13.6±4.8% by topical Ach (10–6 M and 10–5 M, respectively) and by 6.4±2.5% and 12.2±3.1% by topical adenosine (10–5 M and 10–4 M, respectively). One hour after a 1-min inhalation of mainstream smoke (1 mg-nicotine cigarette), 10–5 M Ach constricted cerebral arterioles (−4.4±4.1%), while 10–4 M adenosine dilated them by 13.4±3.4%. One hour after a 1-min nicotine infusion (0.05 mg), 10–5 M Ach dilated cerebral arterioles by 9.9±2.4%. Thus, vasodilator response to topical Ach was impaired after smoking, whereas that to adenosine was unaffected. However, the vasodilator response to Ach was unaffected by intravenous nicotine. Valsartan pretreatment did not change the responses to topical Ach application obtained before smoking. One hour after a 1-min inhalation of mainstream smoke, 10–5 M Ach dilated cerebral pial arteries by 10.9±3.7% in the valsartan pretreatment group, a response that was significantly different from that obtained without valsartan pretreatment. Thus, valsartan completely prevented the smoking-induced impairment of Ach-induced vasodilation.
Conclusion
Acute single-cigarette smoking causes a dysfunction of endothelium-dependent, but not endothelium-independent, vasodilation of rat cerebral vessels in vivo, and the effect was not mimicked by intravenous nicotine. AT1-receptor blockade prevented the above smoking-induced impairment of endothelium-dependent vasodilation (See Figure 1)
