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-142893, a mixed endothelin-A- and -B- (ET(A)/ET(B)) receptor antagonist. Male Wistar rats were chronically instrumented with arterial and venous catheters and a microdialysis probe placed into the adrenal medulla. Stress was induced by a 1 h period of immobilization. PD-142893 was infused (20 microg/kg/min) for 90 min starting 30 min before stress onset. Concentrations of norepinephrine 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 adrenal perfusate and constant haemodynamic parameters. Stress increased adrenal secretion (norepinephrine 206 +/- 50%, epinephrine 202 +/- 45%) associated with hypertension (peak 141 +/- 3 mmHg) and tachycardia (peak 505 +/- 5 bpm). No significant changes in haemodynamics or of plasma catecholamine levels were observed during infusion of PD-142893. The antagonist did not significantly change the stress-induced increase in catecholamine secretion, tachycardia or hypertension. Thus, in Wistar rats, circulating ET-1 seems not to be essential for blood pressure control or adrenal catecholamine secretion during acute stress.
Zaretsky
D V
DV
Cardiology Research Center, Moscow State University, Vorobjovy Gory, Russia.
Zaretskaia
M V
MV
Kalenikova
E I
EI
Grafov
M A
MA
D000208:Acute Disease; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013312:Stress, Physiological / Q000503:physiopathology*
D002395:Catecholamines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C076213:PD 142893