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 investigated whether the acute administration of nicotine changes the hypotensive responses to bradykinin in rats. The effects of pre-treatment with losartan or enalapril on the nicotine-induced changes in the responses to bradykinin were also evaluated. In study 1, anesthetized rats were cannulated via carotid artery for the measurement of mean arterial pressure. Dose-response curves to bradykinin (0.1, 0.4, 1.6, 6.4, 25 and 100 microg/kg) were generated before and 10 min after the injection of nicotine (200 microg/kg, i.v.) or saline. The individual dose-response curves were fitted to a four-parameter logistic equation using the ALLFIT program, which provided an estimate of the maximal response (E(max)) and of the dose of bradykinin producing the half-maximal response (ED(50)). In study 2, rats were pre-treated orally with losartan (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 anesthetized 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 ED(50). 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, respectively; P<0.05) without significantly changing the ED(50). These results suggest that nicotine impairs the endothelium-dependent hypotensive responses to bradykinin. This effect is not influenced by inhibition of the angiotensin-converting enzyme or by blockade of the angiotensin AT(1) receptors.
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), P.O. Box 6111, 13081-970, Campinas, São Paulo, Brazil
M O
MO
Paganelli
J E
JE
Tanus-Santos
J C
JC
Toledo
J F
JF
do Prado
V
V
Calegari
H
H
Moreno
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001920:Bradykinin; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D005731:Ganglionic Stimulants; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D004656:Enalapril; D009538:Nicotine; D019808:Losartan; D001920:Bradykinin