Endothelial cells release both relaxing and contracting factors that modulate vascular smooth muscle tone and also participate in the pathophysiology of essential hypertension. Endothelium-dependent vasodilation is regulated primarily by nitric oxide but also by an unidentified endothelium-derived hyperpolarizing factor and by prostacyclin. Endothelium-derived contracting factors include endothelin-1, vasoconscrictor prostanoids, angiotensin II and superoxide anions. Under physiological conditions, there is a balanced release of relaxing and contracting factors. The balance can be altered in cardiovascular diseases such as hypertension, atherosclerosis, diabetes and other conditions, thereby contributing to further progression of vascular and end-organ damage. In particular, endothelial dysfunction leading to decreased bioavailability of nitric oxide impairs endothelium-dependent vasodilation in patients with essential hypertension and may also be a determinant for the premature development of atherosclerosis. Different mechanisms of reduced nitric oxide activity have been shown both in hypertensive states and several cardiovascular diseases, and endothelial dysfunction is likely to occur prior to vascular dysfunction. Thus, the strategies currently used to improve endothelial dysfunction may result in decreased morbidity and mortality in hypertensive patients.

Patients with advanced cirrhosis frequently show hemodynamic abnormalities. Autonomic dysfunction (AD) is also common and, owing to the importance of autonomic function in cardiovascular homeostasis, it may be involved in the pathogenesis of the hyperdynamic circulation. We, therefore, evaluated the hemodynamic status and autonomic function in 30 patients with cirrhosis, most of them with an advanced stage of the disease. Autonomic function was assessed with 7 cardiovascular tests exploring the vagal or sympathetic function. Each test was scored from 1 to 3 (normal, borderline, altered). Cardiac index (CI) was measured by an echocardiogram. Twenty-four (80%) patients showed an AD, this being definite in 14 (47%) patients. A vagal dysfunction (VD) was found in 19 patients (63%), this being definite in 11 patients (37%), and a sympathetic dysfunction (SD) in 7 patients (definite in 3 [10%] patients). The patients with AD showed a faster heart rate (P ‫؍‬ .021), lower indicized peripheral vascular resistance (P ‫؍‬ .013), and increased CI (P ‫؍‬ .004) than patients without AD whereas mean arterial pressure did not differ. Similar results were seen by grouping patients according to the VD. AD score was directly correlated with heart rate (r ‫؍‬ 0.53; P ‫؍‬ .002) and CI (r ‫؍‬ 0.45; P ‫؍‬ .016), and inversely correlated with peripheral vascular resistance (r ‫؍‬ 0.46; P ‫؍‬ .013). Even closer correlations were found with vagal score. AD (mainly VD) may be involved in the pathogenesis of the hyperdynamic circulatory syndrome of patients with advanced cirrhosis. (HEPATOLOGY 1999;30:1387-1392.)Hyperdynamic circulation is a common and long-recognized feature of patients with advanced cirrhosis, 1 consisting of elevated cardiac rate and output and reduced peripheral vascular resistance, so that arterial pressure is tendentially or frankly reduced. The clinical importance of this disorder was shown by subsequent studies, showing that the alterations of systemic hemodynamics, renal function, and vasoactive systems are prognostic indicators even more accurate than the tests exploring liver function. 2 The setting of the hyperdynamic circulatory syndrome is the pathogenetic background of complications such as renal sodium and water retention and hepatorenal syndrome. 3 Splanchnic blood pooling, opening of portal-systemic collaterals, and arterial vasodilation, as well as a compensatory increase in blood volume, are the causative events of the hyperdynamic circulatory syndrome. 4,5 The pathogenesis of arterial vasodilation is still debated. It has been proposed that an overproduction of a variety of vasorelaxant agents, such as histamine, adenosine, gut-derived peptides and endothelial cell-derived vasodilators, and bile acid retention reduce the responsiveness of the vascular bed to endogenous vasoconstrictor stimuli. 4,6 The autonomic nervous system plays a central role in modulating cardiac performance and vasomotor activity. The presence of an autonomic dysfunction (AD) in cirrhosis has been clearly shown through different...

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To assess the hemodynamic status of patients with compensated cirrhosis, mean arterial pressure, cardiac index and peripheral vascular resistance and markers of central (plasma concentrations of atrial natriuretic factor) and arterial volemia (plasma norepinephrine concentration, plasma renin activity) were studied in 10 patients and 10 healthy control subjects under steady-state conditions (after 2 hr of standing) and after assumption of the supine position (30, 60, and 120 min). After standing, neither hemodynamics nor markers of effective volemia differed significantly between controls and patients. By evaluating the areas under the curve during the 2 hr of supine posture, the increase in cardiac output and plasma natriuretic factor and the decrease in peripheral vascular resistance were greater in patients (2.59 +/- 0.43 [S.E.M.] L/min/hr; 32.8 +/- 7.2 pg/ml/hr -1,103 +/- 248.4 dyn.sec/cm5/hr, respectively) than in controls (0.53 +/- 0.24 L/min/hr, p = 0.005; 17.4 +/- 4.7 pg/ml/hr, p = 0.005; -265.5 +/- 206.2 dyn.sec/cm5/hr, p = 0.02). The declines in heart rate, plasma norepinephrine concentration and plasma renin activity did not differ significantly. Mean arterial pressure did not significantly change. Our results suggest that during periods of upright posture, cirrhotic patients in the preascitic stage, who are known to have expanded blood volume, compensate for dilatation of the splanchnic vascular bed through total hypervolemia. The latter becomes excessive during recumbency, leading to supernormal increases in venous return, central volemia and cardiac index. The decline in peripheral vascular resistance appears to be a compensatory mechanism to maintain steady arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)