Acute administration of nicotine impairs the hypotensive responses to bradykinin in rats

Nicotine may contribute to smoking-induced endothelial dysfunction because of its ability to impair endothelium-dependent vasodilatation. We investiga ted whether the acute administration of nicotine changes the hypotensive re sponses to bradykinin in rats. The effects of pre-treatment with losartan o r enalapril on the nicotine-induced changes in the responses to bradykinin were also evaluated. In study 1, anesthetized rats were cannulated via caro tid artery for the measurement of mean arterial pressure. Dose-response cur ves to bradykinin (0.1, 0.4, 1.6, 6.4, 25 and 100 mug/kg) were generated be fore and 10 min after the injection of nicotine (200 mug/kg, i.v.) or salin e. The individual dose-response curves were fitted to a four-parameter logi stic equation using the ALLFIT program, which provided an estimate of the m aximal response (E-max) and of the dose of bradykinin producing the half-ma ximal response (ED50). In study 2, rats were pre-treated orally with losart an (10 mg/kg/day) or enalapril maleate (25 mg/kg/day) for 2 weeks. Control rats received tap water alone. After pre-treatment, the rats were anestheti zed and used as described in study 1. Nicotine decreased the E-max (from 73 .0 +/- 7.5 to 65.7 +/- 3.3 mm Hg; P < 0.05) but did not affect the ED50. In study 2, losartan or enalapril did not affect nicotine-induced decrease in responses to bradykinin; E-max decreased in both groups (from 68.7 +/- 6.3 to 62.8 +/- 4.2 mm Hg, and from 53.8 +/- 13.0 to 43.1 +/- 7.1 mm Hg, respe ctively; P < 0.05) without significantly changing the ED50. These results s uggest that nicotine impairs the endothelium-dependent hypotensive response s to bradykinin. This effect is not influenced by inhibition of the angiote nsin-converting enzyme or by blockade of the angiotensin AT(1) receptors. ( C) 2001 Elsevier Science B.V. All rights reserved.