infarction, and sudden death [1] . An acute increase in heart rate and arterial pressure mediated by systemic Background. Cigarette smoking is associated with vasoconstriction is usually observed during cigarette acute increase in arterial pressure due to systemic smoking [2] . In addition to the above-mentioned vasoconstriction and decreased skin and coronary effects, nicotine induces a reduction in skin [3] as well blood flow. Virtually all cardiovascular effects of cigaras coronary blood

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... [4] , systemic venoconstriction ette smoking are due to nicotine. However, whether and an increase in muscle blood flow [5] and myocardnicotine also affects the renal circulation and function ial contractility [4] . Whether nicotine affects the renal in humans is at present unknown. circulation and glomerular filtration rate in humans is Methods. In the current study the acute effects of a presently unknown. Of interest, smoking is associated 4-mg nicotine gum on arterial pressure, heart rate as with a larger prevalence of microalbuminuria in normwell as renal haemodynamics and function were otensive and hypertensive subjects [6,7] and a faster assessed in non-smokers and chronic smokers. progression of renal disease [8], as reported in a recent Results. In non-smokers, mean arterial pressure extensive review of the renal risks of smoking [9]. (+8±1 mmHg, P<0.001) and heart rate (+13±3 Since denicotinized cigarettes have no consistent beats/min, P<0.001) increased whereas effective renal cardiovascular effect, it was suggested that the acute plasma flow (ERPF ) and glomerular filtration rate effects of cigarette smoking could be due to nicotine (GFR) decreased by 15±4% and 14±4% respectively; [2, 5] . A role for stimulation of the sympathetic nervous in addition, urinary cyclic GMP decreased by 51±12% system and vasopressin release in the vasoconstrictor in response to nicotine administration. In smokers, effect of nicotine was demonstrated [3, 10]. Recent studies mean arterial pressure and heart rate increased simhave shown that the release of vasoactive substances ilarly; however, in contrast with non-smokers, ERPF including nitric oxide (NO) by endothelial cells may and GFR remained unchanged whereas urinary cyclic participate to the regulation of systemic as well as GMP rose by 87±43%. Changes in ERPF induced by regional vascular tone [11]. Since nitric oxide-dependent nicotine were positively correlated with changes in vasodilatation assessed through the vasodilatory effect urinary cyclic GMP. of acetylcholine is attenuated in chronic smokers Conclusions. These findings indicate that nicotine [12][13][14], the role of nicotine remains to be demonstrated. administration is associated with renal vasoconstriction In most studies, the effects of nicotine was assessed in healthy non-smokers, possibly through alteration in habitual cigarette smokers; however, because of the of a cyclic-GMP-dependent vasoactive mechanism. eventual development of tolerance to nicotine [15], Tolerance to the renal effect of nicotine was observed these effects may not be identical in non-smokers. in chronic smokers, despite the maintenance of the In the present studies, the systemic and renal effects systemic response to nicotine. of a 4-mg nicotine gum were evaluated in non-smokers and habitual cigarette smokers. In addition, a possible Key words: cyclic GMP; humans; nicotine; renal role for the nitric oxide/atrial natriuretic peptide pathway was investigated through the determination of haemodynamics; smoking urinary excretion of cyclic guanosine monophosphate (cGMP) considered as the marker of the interaction betwen nitric oxide/atrial natriuretic peptide and effector cells [11,16,17].