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Letters to the Editor |
2nd Dept. of Intern. Med., University of Rome "La Sapienza", Rome, Italy
a Address correspondence to this author, at: 2a Clinica Medica, Policlinico Umberto I, 00185 Rome, Italy.
To the Editor:
Endothelin-1 (ET-1) is a potent vasoconstrictive peptide originally isolated from the supernatant of cultured porcine endothelial cells (1). ET-1 has not only contractile effects but also growth effects on both smooth muscle and heart muscle cells in vitro (2). Studies have shown that some substances (1)(3), e.g., vasopressin (4), stimulate the release of immunoreactive ET-1 from cultured bovine carotid endothelial cells.
Smoking is known to induce a variety of effects in the cardiovascular and hormonal systems in humans (5)(6)(7)(8)(9)(10). Administration of nicotine causes the release of some hormones (9)(10) and produces increases in blood pressure, heart rate, cardiac output, and oxygen consumption (5)(6)(7)(8). Recently, Yildiz et al. (11) reported that heavy cigarette smokers had higher plasma ET-1 concentrations than either light smokers or controls. In another study, Haak et al. (12) stated that after a short-term tobacco consumption the plasma concentrations of ET-1 significantly increased within 10 min of smoking.
Although tobacco smoke contains other compounds, besides nicotine and carbon monoxide, we decided to test in 10 healthy nonsmoker volunteers (all medical students, 5 men and 5 women, ages 21–24 years) the acute effect of nicotine chewing gum (Nicorette, supplied by Pierrel Pharmaceutical) on plasma ET-1 concentrations. Each piece of chewing gum contained 2 mg of nicotine. We also measured the plasma concentrations of the vasoconstrictor peptide vasopressin, also known to act on the cardiovascular system.
On the day of the study, fasting subjects arrived between 0800 and 0900. At the time of collecting venous samples, all subjects had been kept in supine position for at least 30 min to stabilize their physical condition. Before and 5, 15, 30, and 60 min after the subjects chewed the nicotine gum, venous blood samples were collected in ice-chilled EDTA-coated tubes and centrifuged at 3000g for 30 min; the plasma obtained was frozen and stored at -70 °C until assayed. At the same intervals, the subjects' blood pressure and pulse rate were monitored. After 1 week, all volunteers repeated the experimental study but with a placebo gum that looked the same as the nicotine gum.
Plasma ET-1 was assayed with a specific RIA (RIC-6901; Peninsula Lab., Belmont, CA), as previously described (13). Vasopressin was also measured with an RIA (RK-065–07 Phoenix Pharmaceuticals, Mountain View, CA). Briefly, vasopressin was extracted from samples with a C18 Sep-Pak column after acidification with 5 mL of 1 g/L trifluoroacetic acid and was eluted with 4 mL of acetonitrile:water (50:50 by vol). The residue was dissolved in 0.3 mL of 50 mmol/L phosphate buffer (pH 7.4) and assayed by RIA with radioiodinated vasopressin and antiserum against synthetic vasopressin in rabbits.
For statistical evaluation, we used ANOVA, followed by Bonferroni's correction. Results are presented as mean ± SD.
Nicotine gum was well-tolerated, but 2 subjects had local mouth
irritation. All volunteers had significantly increased mean plasma ET-1
values within 15 min after chewing the nicotine gum (P
<0.0001), whereas the vasopressin values increased 5 min after this
oral nicotine administration (P <0.002) (Table 1
). Oral nicotine consumption was associated with significant
increases in the mean pulse rate (P <0.001) and systolic
(P <0.005) and diastolic (P <0.001) blood
pressure 15 min after the start of nicotine gum administration,
compared with the basal values: 76.2 ± 2.5 beats/min, 125.5
± 8 mmHg, and 86.1 ± 3.3 mmHg vs 69.7 ± 2.4 beats/min,
118.3 ± 2.5 mmHg, and 80.1 ± 3.5 mmHg, respectively.
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In addition, the correlation between ET-1 and vasopressin plasma
concentrations 60 min after nicotine gum administration was
statistically significant (r = 0.695, P
= 0.038). As reported in Table 1
, plasma ET-1 and vasopressin
concentrations and the hemodynamic measurements remained unchanged
during the placebo experiment.
ET-1 is one of the most potent vasoconstrictors (10 times more potent than angiotensin II, vasopressin, and neuropeptide Y) (1), and its expression by endothelial cells is regulated by other vasoactive agents (1)(3)(4). Thus, vasopressin rapidly (within 5 min) induces the expression of pro-pre-endothelin-1 mRNA and secretion of ET-1 from a cultured bovine carotid endothelial cells (14).
Our results indicate that acute nicotine consumption induces in nonsmoking healthy subjects an increase in plasma ET-1 concentrations and that this increase follows a prompt rise of plasma vasopressin. These data suggest that, at least in part, the acute consumption of nicotine stimulates the release of circulating ET-1 via vasopressin activation. Therefore, the alterations in plasma ET-1 secretion induced by nicotine consumption might contribute to the pathogenesis of several cardiovascular disorders, in view of the powerful vasoconstrictor and growth-promoting properties of the peptide. Additional studies are required to describe the effects of nicotine gum in smokers.
References
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