Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Sympathetic neural responses to smoking are age dependent Dagmara Hering a , Virend K. Somers b , Tomas Kara b , Wieslawa Kucharska a , Pavel Jurak b , Leszek Bieniaszewski a and Krzysztof Narkiewicz a,b Objective Smoking is an important risk factor for cardiovascular disease. Sympathetic responses to cigarette smoking may be implicated in the link between smoking and cardiovascular disease. We tested the hypothesis that the sympathetic neural responses to smoking are age dependent. Methods We examined the effects of cigarette smoking and sham smoking on muscle sympathetic nerve activity, blood pressure and heart rate in 14 normotensive middle-aged (49 W 4 years) and 12 young (29 W 4 years) habitual smokers matched for body mass index (25 W 2 kg/m 2 in both groups). Results Sham smoking had no significant effect on sympathetic drive, blood pressure or heart rate in either group. Cigarette smoking increased heart rate in both middle-aged subjects and young subjects. In comparison to younger subjects, middle-aged smokers showed similar smoking-related increases in systolic blood pressure (SBP) [10 W 3 versus 12 W 2 mmHg, respectively, not significant (NS)]. Smoking decreased sympathetic nerve activity by 28 W 12% of baseline values (P < 0.01) in young subjects. However, muscle sympathetic nerve activity did not change significantly after smoking in middle-aged subjects (5 W 8%, NS), despite the increased blood pressures, which would be expected to inhibit sympathetic activity. By contrast, in young subjects, the heart rate increase (22 W 2 bpm) was greater than that seen in middle-aged subjects (13 W 2 bpm, P < 0.01). Conclusions The autonomic responses to smoking are age dependent. While blood pressure increases are similar in both groups, young subjects respond to smoking by marked increases in heart rate and suppression of central sympathetic outflow. In middle-aged subjects, the heart rate increase is less marked, but sympathetic vasoconstrictor activity is not suppressed. J Hypertens 24:691–695 Q 2006 Lippincott Williams & Wilkins. Journal of Hypertension 2006, 24:691–695 Keywords: age, cardiovascular disease, heart rate, smoking, sympathetic nervous system a Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland and b Divisions of Cardiovascular Disease and Hypertension, Mayo Clinic, Rochester, Minnesota, USA Correspondence and requests for reprints to Krzysztof Narkiewicz, Department of Hypertension and Diabetology, Akademia Medyczna w Gdansku, Debinki 7c, 80-952 Gdansk, Poland Tel: +48 58 349-2527; fax: +48 58 349-2601; e-mail: knark@amg.gda.pl Sponsorship: This work was supported by NIH HL61560 and NIH FIRCA Award R03 TW0 1148. Received 12 October 2005 Revised 3 December 2005 Accepted 27 December 2005 Introduction Smoking is an important risk factor for cardiovascular disease, in particular for acute events such as myocardial infarction, stroke and sudden death [1–3]. Among smokers, cardiac ischemia is five times more likely when patients are actually smoking, than when they are not smoking [4], demonstrating the importance of acute effects of cigarette smoke. The risk of myocardial infarc- tion in smokers is much higher than the risk in non- smokers with more extensive coronary artery disease [5]. The risk of sudden death increases more than tenfold in men and fivefold in women who smoke [6]. The mechanisms of any acute triggering effect of cigarette smoking are not well understood. However, a common feature of several suggested mechanisms is a smoking-initiated activation of the sympathetic nervous system. In healthy young subjects, smoking leads to an increase in blood pressure and an inhibition of muscle sympathetic nerve activity (MSNA) [7–10]. Increased blood pressure during smoking, acting via the barore- flexes, may cause sympathetic inhibition and thus obscure any sympathetic activation due to cigarette smoke [9]. Sympathetic activity increases progressively with aging. Smoking is associated with cardiovascular disease across different ages, but the increase in relative risk is particularly striking in middle-aged subjects [1,2]. Whether middle-aged subjects, who are most vulnerable to smoking-related acute cardiovascular events, have a differential response to cigarette smoking in comparison to healthy young subjects has not been studied pre- viously. We therefore tested the hypothesis that sym- pathetic neural responses to smoking in habitual smokers are age dependent. Methods Subjects We studied 14 normotensive middle-aged (49  4 years, mean  SD, eight males and six females) and 12 young (29  4 years, seven males and five females) habitual smokers (smoking 10–20 cigarettes/day for more than 2 years) matched for body mass index (25  2 kg/m 2 in Original article 691 0263-6352 ß 2006 Lippincott Williams & Wilkins