Effect of ET(A) receptor antagonists on cardiovascular responses induced by centrally administered sarafotoxin 6b: Role of sympathetic nervous system

Ashok Kumar, Shaun Morrison, Anil Gulati

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The present study was carried out to investigate the cardiovascular effects of centrally administered SRT6b in saline, BQ123 and BMS182874 pretreated male Sprague-Dawley rots, using a radioactive microsphere technique. SRT6b (100 ng, ICV) produced a transient increase (40%) in blood pressure at 5 min followed by a sustained decrease (-42%) at 30 and 60 min in control rats. Total peripheral resistance and heart rate were not significantly altered. Cardiac output increased (16%) at 5 min and decreased 30 and 60 min following SRT6b administration. Central venous pressure was not affected by SRT6b. Regional blood flow and vascular resistance did not change at 5 min following administration of SRT6b. However, a significant decrease in blood flow to the brain, heart, kidneys, liver, spleen, gastrointestinal tract and mesentery and pancreas was observed 30 and 60 min following administration of SRT6b in control (saline treated) rats. Pretreatment with ET(A) selective receptor antagonists, BQ123 (10 μg, ICV) or BMS182874 (50 μg, ICV) significantly attenuated the presser and depressor effects of centrally administered SRT6b. SRT6b induced decrease in blood flow was completely blocked by pretreatment with BQ 123 or BMS182874. ET-1 (100 ng, ICV) produced an increase followed by a decrease similar to SRT6b. Reserpine (5 mg/kg, IP) pretreatment attenuated the cardiovascular effects of ET-1. Role of sympathetic nervous system was determined by measuring splanchnic nerve activity. SRT6b when administered in the lateral cerebral ventricle did not produce any significant effect at 5 min, however, a significant decrease in sympathetic nerve activity was observed 30 min after its administration. It is concluded that centrally administered SRT6b produces significant changes in systemic and regional blood circulation which can be completely blocked by ET(A) receptor antagonist. The cardiovascular effects of centrally administered SRT6b appear to be mediated through the sympathetic nervous system.

Original languageEnglish (US)
Pages (from-to)855-864
Number of pages10
JournalPeptides
Volume18
Issue number6
DOIs
StatePublished - Jan 1 1997

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Keywords

  • Blood pressure
  • Cardiovascular system
  • Central nervous system
  • ET(A) receptor antagonist
  • Endothelin
  • Regional blood flow
  • Sarafotoxin
  • Sprague- Dawley rats

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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