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

D. V. Zaretsky, M. V. Zaretskaia, E. I. Kalenikova, M. A. Grafov

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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 μg/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.

Original languageEnglish (US)
Pages (from-to)S374-S376
JournalJournal of cardiovascular pharmacology
Volume36
Issue number5 SUPPL. 1
DOIs
StatePublished - Jan 1 2000

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Keywords

  • Adrenal medulla
  • Cardiovascular system
  • Catecholamines
  • Endothelin
  • Rats

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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