Endothelin antagonism does not affect adrenal catecholamine secretion and system haemodynamics during acute stress in Wistar rats

In the present work we evaluated the role of circulating endothelin-1 (ET-1 ) in haemodynamics and the adrenal medulla responses to stress using PD-142 893, a mixed endothelin-A- and -B- (ETA/ETB) receptor antagonist. Male Wist ar rats were chronically instrumented with arterial and venous catheters an d a microdialysis probe placed into the adrenal medulla. Stress was induced by a 1 h period of immobilization. PD-142893 was infused (20 mug/kg/min) f or 90 min starting 30 min before stress onset. Concentrations of norepineph rine and epinephrine in dialysate samples were measured by high-performance liquid chromatography (HPLC). At rest animals displayed a stable level of norepinephrine (85 +/- 34 pg/ml) and epinephrine (176 +/- 57 pg/ml) in adre nal perfusate and constant haemodynamic parameters. Stress increased adrena l secretion (norepinephrine 206 +/- 50%, epinephrine 202 +/- 45%) associate d with hypertension (peak 141 +/- 3 mmHg) and tachycardia (peak 505 +/- 5 b pm). No significant changes in haemodynamics or of plasma catecholamine lev els were observed during infusion of PD-142893. The antagonist did not sign ificantly change the stress-induced increase in catecholamine secretion, ta chycardia or hypertension. Thus, in Wistar rats, circulating ET-1 seems not to be essential for blood pressure control or adrenal catecholamine secret ion during acute stress.