Comparison of selective arginine vasopressin V1 and V2 receptor antagonists on burn shock in the rat.

STUDY OBJECTIVE

Two selective V1 and V2 receptor antagonists of arginine vasopressin, d(CH2)5Tyr(Me)AVP and d(CH2)5[D-Ile2, Ile4, Ala9-NH2]AVP, were given intravenously in burn shocked rats to investigate the respective effects of V1 and V2 receptor blockade on the haemodynamic variables in burn shock.

DESIGN

Computer assisted on line real time measurements of mean arterial blood pressure, diastolic blood pressure, left ventricular systolic pressure, dP/dtmax, and heart rate were used to study the effects of the receptor antagonists during burn shock. In addition, the radioactive microsphere method was used to measure the changes of cardiac output and regional blood flows to heart, kidney, and liver in response to the antagonists during burn shock. Third degree burns extending over 30% of body surface area were made by dipping the rat's shaved back into water at 100 degrees C for 20 s.

EXPERIMENTAL MATERIAL

Male Sprague-Dawley rats (250-300 g) were used in groups of 6-9 per experiment.

MEASUREMENTS AND MAIN RESULTS

Mean and diastolic arterial blood pressures, left ventricular systolic pressure, dP/dtmax and heart rate were measured for 8 h after burns. Cardiac output and regional blood flow were measured at 3 h and 8 h postburn. Results showed that blockade of V1 receptor lowered mean and diastolic arterial blood pressures throughout the 8 h period, and raised left ventricular systolic pressure and dP/dtmax only during the early phase of shock. Cardiac output and blood flows to heart, kidney, and liver were increased by the V1 antagonist at 3 h but not at 8 h postburn. The V2 receptor antagonist increased mean and diastolic arterial blood pressures, left ventricular systolic pressure, and dP/dtmax both during the early and during the late phases of burn shock. It also improved cardiac output and blood flows to the heart, kidney, and liver during the early and late phases of burn shock. However, heart rate was not affected by V1 and V2 receptor antagonists.

CONCLUSIONS

The V2 like receptor may be the dominating receptor mediating vasopressin's inhibitory effect on the heart. V1 receptor mediated coronary vasoconstriction contributes to the myocardial depression possibly only at the compensatory phase of shock. In addition V1 receptor mediated vasoconstriction is important in maintaining blood pressure during burn shock.