Hormonal, global, and regional haemodynamic responses to a vascular antagonist of vasopressin in patients with congestive heart failure with and without hyponatraemia.

Abstract

The pathophysiological role of an increase in circulating vasopressin in sustaining global and regional vasoconstriction in patients with congestive heart failure has not been established, particularly in patients with hyponatraemia. To assess this further, 20 patients with congestive heart failure refractory to digoxin and diuretics were studied before and 60 minutes after the intravenous injection (5 micrograms/kg) of the vascular antagonist of vasopressin [1(beta-mercapto-beta,beta-cyclopentamethylene-propionic acid), 2-(0-methyl) tyrosine] arginine vasopressin. Ten patients were hyponatraemic (plasma sodium less than 135 mmol/l) and 10 were normonatraemic. In both groups of patients the vascular vasopressin antagonist did not alter systemic or pulmonary artery pressures, right atrial pressure, pulmonary capillary wedge pressure, cardiac index, or vascular resistances. Furthermore, there was no change in skin and hepatic blood flow in either group after the injection of the vascular antagonist. Only one patient in the hyponatraemic group showed considerable haemodynamic improvement. He had severe congestive heart failure and a high concentration of plasma vasopressin (51 pmol/l). Plasma renin activity, vasopressin, or catecholamine concentrations were not significantly changed in response to the administration of the vasopressin antagonist in either the hyponatraemic or the normonatraemic groups. Patients with hyponatraemia, however, had higher baseline plasma catecholamine concentrations, heart rate, pulmonary pressure and resistance, and lower hepatic blood flow than patients without hyponatraemia. Plasma vasopressin and plasma renin activity were slightly, though not significantly, higher in the hyponatraemic group. Thus the role of vasopressin in sustaining regional or global vasoconstriction seems limited in patients with congestive heart failure whether or not concomitant hyponatraemia is present. Vasopressin significantly increases the vascular tone only in rare patients with severe congestive heart failure and considerably increased vasopressin concentrations. Patients with hyponatraemia do, however, have raised baseline catecholamine concentrations, heart rate, pulmonary arterial pressure and resistance, and decreased hepatic blood flow.

Arginine Vasopressin Levels Are Elevated and Correlate With Functional Status in Infants and Children With Congestive Heart Failure

“…Pharmacological blockade of AVP receptors has therefore become an attractive method of improving symptomatology and functional class in adults with heart failure. 8,[11][12][13] To date, very limited data exist on secretion of AVP in infants and children with heart failure. 14 The purpose of the present study was to determine whether AVP levels are elevated in children with CHF attributable to left ventricular dysfunction or symptomatic pulmonary overcirculation attributable to large left-to-right intracardiac shunts and to determine whether AVP levels correlate with functional clinical status in patients with ventricular dysfunction.…”

Conivaptan: A Dual Receptor Vasopressin V1a/V2 Antagonist

“…Unfortunately, although these agents antagonized pressor and antidiuretic responses in animals, they were found to have a paradoxical weak agonism in humans (Verbalis et al 2002). In addition, these compounds had short biological half‐lives and poor oral bioavailability (Nicod et al 1985; Verbalis et al 2002). In 1991, the first nonpeptide AVP receptor antagonist was discovered in Japan (Yamamura et al 1991).…”

The Role of Neuroendocrine Abnormalities in the Enhanced Sodium and Water Retention of Chronic Heart Failure

“…Consequently, specific antagonists of the vascular effects of AVP have been developed and used in CHF. As yet there are no reports of attempts to block the renal effects of AVP in CHF (Creager et al 1986;Nicod et al 1986). …”

“…Consequently, specific antagonists of the vascular effects of AVP have been developed and used in CHF. As yet there are no reports of attempts to block the renal effects of AVP in CHF (Creager et al 1986;Nicod et al 1986). Dzau et al (1984) have reported that the metabolites of the prostaglandins PGI2 and PGEz in patients with CHF reach 3-10 times the levels of those found in normal subjects.…”