Effects of cilazaprilat and enalaprilat on the sympathetically mediated pressor response in pithed rats

S. Satoh, F. Yoneyama, Mizue Kusaba

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1 Citation (Scopus)

Abstract

A study was conducted to investigate the possibility that the angiotensin-converting enzyme (ACE) inhibitors, cilazaprilat (CIL) and enalaprilat (ENA), may interfere with sympathetic neurogenic vasoconstriction by acting on the facilitatory interaction between angiotensin II (AII) and the sympathetic nervous system in pithed rats. CIL and ENA (10 μg kg-1 and an additional dose of 30 μg kg-1, i.v.) dose-relatedly inhibited the pressor response to angiotensin I (0.3-3.0 μg kg-1, i.v.) without altering the pressor response to AII (1.0 μg kg-1, i.v.). The pressor response to spinal sympathetic nerve stimulation (NS, 1-10 Hz) was dose-relatedly attenuated by both ACE inhibitors (10 μg kg-1 and an additional dose of 30 μg kg-1, i.v.). However, the pressor response to injected norepinephrine (NE, 0.1-3.0 μg kg-1) tended to be attenuated, but the extent of inhibition was not significant. During subsequent infusion of AII (160 ng kg-1 min-1, i.v.), the markedly attenuated response to NS was potentiated and restored to the initial control response, while the response to NE attained a slightly higher level than the initial control response. In rats that had been bilaterally nephrectomized 18 to 24 h previously, the pressor response to either NS or NE was smaller than that in rats with intact kidneys, although there was a greater difference in the response to NS. The pressor response to either NS or NE, which was virtually unaltered by ACE inhibitor, was potentiated upon subsequent infusion of AII into bilaterally nephrectomized rats. These results suggest that the ACE inhibitors, CIL and ENA, attenuate the pressor response elicited by spinal sympathetic nerve stimulation through the inhibition of endogenous AII formation in pithed rats, in which endogenous AII may exert a facilitatory interaction with sympathetic functions.

Original languageEnglish
Pages (from-to)231-239
Number of pages9
JournalAsia Pacific Journal of Pharmacology
Volume3
Issue number4
Publication statusPublished - 1988 Jan 1

ASJC Scopus subject areas

  • Pharmacology

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