vasopressin--1-(1-mercaptocyclohexaneacetic-acid)-2-(o--methyl-l-tyrosine)-8-l-arginine- and Heart-Failure

The pressor action of vasopressin (AVP) in humans was investigated with the specific anti-vasopressor V1 antagonist d(CH2)5-O(Me)-Tyr-AVP. A single 0.5-mg intravenous bolus of this agent inhibited the pressor effect of AVP by about 80%. Normally hydrated humans had no blood pressure response to this dose, but this agent did prevent the blood pressure rise in response to exogenous AVP given in doses up to 200 milli-units/kg. Patients with severe hypertension, especially that associated with end-stage renal disease, tended to respond with moderate increases in blood pressure and plasma AVP after sodium overload and had a modest blood pressure fall (10-20 mmHg) in response to a single intravenous bolus of the AVP antagonist. Patients with an impaired sympathetic nervous system had increased sensitivity to the pressor action of AVP, in keeping with knowledge derived from experimental studies. These data suggest an interaction between AVP and alpha-adrenergic function, whereby the latter tends to attenuate the pressor action of AVP although it facilitates the release of AVP in response to various stimuli. In patients with congestive heart failure, the direct pressor action of AVP appears to contribute to increased systemic vascular resistance in about 30% of cases, i.e., those with plasma AVP concentrations well above the normal range. In these subjects, circulating AVP concentrations correlated with a decrease in vascular resistance in response to the V1 antagonist.

Topics: Animals; Arginine Vasopressin; Clinical Trials as Topic; Heart Failure; Humans; Hypertension; Sympathetic Nervous System; Vasopressins

The effect of circulating arginine vasopressin (AVP) on blood pressure, heart rate, and skin blood flow was assessed in normotensive subjects, mild hypertensive patients, and patients with congestive heart failure, utilizing the specific antagonist of AVP at the vascular receptor level, d(CH2)5Tyr(Me)AVP (5 micrograms/kg i.v.). The renin system of the normal volunteers treated with the AVP antagonist was either intact or acutely blocked with the angiotensin converting-enzyme inhibitor captopril (25 mg p.o.). In some volunteers, the cardiovascular effect of AVP released by Finnish sauna or cigarette smoking was studied. In patients with congestive heart failure, hemodynamic measurements (pressures and cardiac output) were obtained invasively. Acute blockade of AVP vascular receptors produced no cardiovascular effect unless plasma AVP levels were markedly elevated. In our experience, abnormally high circulating AVP appears to be responsible for the decrease in skin blood flow induced by cigarette smoking and to some extent for the maintenance of vascular tone in the rare patients with particularly severe congestive heart failure.

Topics: Angiotensin II; Arginine Vasopressin; Heart Failure; Hemodynamics; Humans; Hypertension; Smoking; Steam Bath; Vasopressins

Ten patients with advanced congestive heart failure were treated with an arginine vasopressin V1 antagonist during hemodynamic monitoring to determine the contribution of vasopressin to vasoconstriction in this disorder. The vasopressin antagonist caused a decrease in systemic vascular resistance in the three patients whose plasma vasopressin was greater than 4.0 pg/ml (average for the group was 2.4 +/- 0.6). Plasma vasopressin concentration correlated with the percent decrease of systemic vascular resistance (r = 0.70, p less than 0.025), serum sodium (r = 0.72, p less than 0.02) and serum creatinine (r = 0.85, p less than 0.005). To compare the relative roles of vasopressin, the renin-angiotensin system and the sympathetic nervous system, these patients also received captopril and phentolamine. Captopril decreased systemic vascular resistance by 20% (p less than 0.05), mostly in patients with high plasma renin activity. Levels of plasma renin activity ranged between 1 and 46 ng/ml per h (average 14.7 +/- 5.7) and correlated with serum sodium (r = 0.77, p less than 0.025), serum creatinine (r = 0.73, p less than 0.025) and right atrial pressure (r = 0.67, p less than 0.05). Phentolamine decreased systemic vascular resistance in all patients (average 34%, p less than 0.01), but the decrease did not correlate with the pretreatment norepinephrine concentration. Norepinephrine levels were elevated in all patients (694 +/- 110 pg/ml) and correlated with baseline stroke volume index (r = 0.75, p less than 0.025) and plasma renin activity (r = 0.67, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Arginine Vasopressin; Captopril; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Phentolamine; Renin; Renin-Angiotensin System; Sympathetic Nervous System; Vascular Resistance; Vasoconstriction; Vasopressins

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.

Topics: Adult; Aged; Arginine Vasopressin; Female; Heart Failure; Hemodynamics; Humans; Hyponatremia; Male; Middle Aged; Time Factors

To assess the role of vasopressin (AVP) in congestive heart failure (CHF), we investigated 10 patients with CHF refractory to conventional treatment, before and 60 minutes after intravenous administration of 5 micrograms/kg of d(CH2)5Tyr(Me)AVP, a specific antagonist of AVP at the vascular receptor level. Heart rate, systemic arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index by thermodilution, and cutaneous blood flow by laser-Doppler technique were measured. In 9 patients there was no significant hemodynamic and cutaneous blood flow response to the AVP antagonist. Plasma AVP was 2.3 +/- 0.8 pg/ml and plasma osmolality 284 +/- 14 mosm/kg H2O. The tenth patient had the most severe CHF. His plasma AVP was 55 pg/ml and plasma osmolality 290 mosm/kg. He responded to the AVP antagonist with a marked decrease in systemic arterial pressure from 115/61 to 79/41 mm Hg, in pulmonary arterial pressure from 58/31 to 33/13 mm Hg and in pulmonary capillary wedge pressure from 28 to 15 mm Hg. Simultaneously cardiac index increased from 1.1 to 2.21 X min-1 X m-2 and cutaneous blood flow rose 5-fold. Thus, most patients with CHF have only moderately elevated plasma AVP and its role in determining peripheral vascular resistance appears to be limited. AVP may become important in rare patients presenting with marked hemodynamic instability and very high plasma AVP.

Topics: Adult; Arginine Vasopressin; Female; Heart Failure; Hemodynamics; Humans; Male; Osmolar Concentration; Vasopressins

To assess the role of arginine vasopressin (AVP) in congestive heart failure (CHF), 10 patients with CHF refractory to conventional treatment were studied before and 60 minutes after intravenous administration of 5 micrograms/kg of d(CH2)5Tyr(Me)AVP, a specific antagonist of AVP at the vascular receptor level. Heart rate, systemic arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index by thermodilution and cutaneous blood flow by laser-Doppler technique were measured. In 9 patients with no significant hemodynamic and cutaneous blood flow response to the AVP antagonist, baseline values (mean +/- standard deviation) were: heart rate, 77 +/- 14 beats/min; systemic arterial pressure, 120/79 +/- 18/8 mm Hg; pulmonary arterial pressure, 42/21 +/- 12/8 mm Hg; pulmonary capillary wedge pressure, 19 +/- 7 mm Hg; cardiac index, 2.2 +/- 0.6 liters/min/m2; plasma AVP, 2.3 +/- 0.8 pg/ml; and plasma osmolality, 284 +/- 14 mosm/kg H2O. The tenth patient had the most severe CHF. His plasma AVP level was 55 pg/ml and plasma osmolality was 290 mosm/kg. He responded to the AVP antagonist with a decrease in systemic arterial pressure from 115/61 to 79/41 mm Hg, in pulmonary arterial pressure from 58/31 to 33/13 mm Hg and in pulmonary capillary wedge pressure from 28 to 15 mm Hg. Simultaneously, cardiac index increased from 1.1 to 2.2 liters/min/m2 and heart rate from 113 to 120 beats/min; cutaneous blood flow increased 5-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Arginine Vasopressin; Blood Pressure; Cardiac Output; Epinephrine; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Regional Blood Flow; Renin; Skin