BACKGROUND Smoking is a major risk factor for the development of atherosclerosis. Because endothelial dysfunction may be a marker for future atherosclerosis, we investigated the effects of smoking on endothelium-dependent control of vascular tone. METHODS AND RESULTS The effects of brachial arterial infusions of NG-monomethyl-L-arginine (L-NMMA), a nitric oxide synthesis inhibitor; sodium nitroprusside; endothelin-1; and norepinephrine on forearm blood flow (strain-gauge plethysmography) were compared in 29 long-term smokers and 16 nonsmokers. The acute effects of smoking on systemic hemodynamics, plasma catecholamines, and forearm vascular responses to these compounds were investigated in smokers only. Smokers did not differ from nonsmokers (n = 16) regarding the vascular effects of sodium nitroprusside (n = 13) or vasoconstriction due to norepinephrine and endothelin-1 (n = 16). Low-dose endothelin-1-induced vasodilation, believed to reflect endothelial prostacyclin or nitric oxide release, was absent in smokers (n = 16), and their increase of forearm vascular resistance (FVR) after L-NMMA (n = 13) was impaired (35.6 +/- 27.9% versus 118.8 +/- 43.2%, P < .001). Short-term smoking (n = 11) increased blood pressure, heart rate, and plasma epinephrine concentrations (P < .05 or less); enhanced endothelin-1-induced vasoconstriction (delta FVR, 457 +/- 192% versus 254 +/- 143%, P < .01); and decreased norepinephrine-induced vasoconstriction (P < .05), but had no effect on the other interventions. CONCLUSIONS Long-term smoking is associated with a diminished nitric oxide-dependent component of basal vascular tone and an impaired endothelium-dependent vasodilator response to low-dose endothelin-1 and short-term smoking enhances endothelin-1-induced vasoconstriction. Impaired endothelial control of vascular tone might reflect impairment of normal antiatherosclerotic endothelial functions in smokers, but the relevance of smoking-induced enhancement of endothelin-1 vasoconstriction remains to be determined.

To define the relation between atrial pressures and the release of atrial natriuretic peptide, we measured plasma concentrations of the peptide in 26 patients with cardiac disease--11 with normal atrial pressures and 15 with elevated atrial pressures (11 of these 15 had elevated pressures in both atria). Mean peptide levels (+/- SEM) in the peripheral venous blood were increased in the 11 patients with cardiac disease and normal atrial pressures, as compared with 60 healthy controls (48 +/- 14 vs. 17 +/- 2 pmol per liter). In the patients with elevated atrial pressures, peptide concentrations were increased twofold in peripheral venous, right atrial, pulmonary arterial, and systemic arterial plasma, as compared with the concentrations in the patients with normal atrial pressures. A step-up in peptide concentration was seen between the venous and right atrial plasma (P less than 0.002) and between the pulmonary and systemic arterial plasma (P less than 0.01), suggesting release of the peptide from the atria. A linear relation was found between right atrial pressure and right atrial peptide concentration (r = 0.835, P less than 0.001) and between pulmonary wedge pressure and the systemic arterial peptide concentration (r = 0.866, P less than 0.001). Right atrial pressure and the peptide concentration both increased with exercise testing in the nine patients evaluated. We conclude that the release of atrial natriuretic peptide is at least partly regulated by right and left atrial pressures. Distinguishing the relative contributions of the two atria and defining the role of peptide release in the pathogenesis of heart failure will require further investigation.

In view of the high risk of sudden cardiac death and the prognostic importance of complex ventricular ectopic activity, the effects of prophylactic antiarrhythmic treatment were investigated prospectively in patients with persisting asymptomatic complex arrhythmias after myocardial infarction. End points were total mortality and arrhythmic events (sudden death, sustained ventricular tachycardia and ventricular fibrillation). Of 1,220 consecutively screened survivors of myocardial infarction, 312 had Lown class 3 or 4b arrhythmia on 24 h electrocardiographic recordings before hospital discharge and consented to the study. They were randomized to individualized antiarrhythmic treatment (Group 1, n = 100), treatment with low dose amiodarone, 200 mg/day (Group 2, n = 98) or no antiarrhythmic therapy (Group 3 [control group], n = 114). During the 1 year follow-up period, 10 patients in Group 1 died, as did 5 in Group 2 and 15 in Group 3. On the basis of an intention to treat analysis, the probability of survival of patients given amiodarone was significantly greater than that of control patients (p less than 0.05). In addition, arrhythmic events were significantly reduced by amiodarone (p less than 0.01). These effects were less marked and not significant for individually treated patients (Group 1). These findings suggest that low dose amiodarone decreases mortality in the 1st year after myocardial infarction in patients at high risk of sudden death.

To determine the effects of age on the pulmonary circulation at rest and on exercise we analysed the results of right heart catheterization studies performed in 125 asymptomatic subjects aged 14-68 years, who were healthy or had indispositions which did not impair cardiac or pulmonary function. Age accounted for less than 10% of total variation in resting values of right atrial, pulmonary artery and wedge pressures, and of cardiac output. The pulmonary artery-wedge pressure gradient and flow resistance at rest significantly increased with age. On exercise there were significant increases with age in right atrial, pulmonary artery and wedge pressures, pulmonary to wedge pressure gradient and flow resistance, but cardiac output was not influenced by age. Pulmonary circulation variables at rest are mainly influenced by sex and size, but during exercise significant effects of age are apparent.