Effect of protein kinase C inhibitors on endothelin- and vasopressin-induced constriction of the rat basilar artery

Margaret A Murray; Frank M Faraci; Donald D Heistad

doi:10.1152/ajpheart.1992.263.6.H1643

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Effect of protein kinase C inhibitors on endothelin- and vasopressin-induced constriction of the rat basilar artery

Journal article

Peer reviewed

Effect of protein kinase C inhibitors on endothelin- and vasopressin-induced constriction of the rat basilar artery

Margaret A Murray, Frank M Faraci and Donald D Heistad

The American journal of physiology, Vol.263(6 Pt 2), pp.H1643-H1649

12/1992

DOI: 10.1152/ajpheart.1992.263.6.H1643

PMID: 1481891

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Abstract

The goal of this study was to determine whether inhibitors of protein kinase C (PKC) attenuate constrictor responses of the basilar artery in vivo to endothelin and arginine vasopressin. In anesthetized rats, the diameter of basilar arteries was measured through a cranial window [control diameter 218 +/- 3 (SE) microns]. Vessel diameter was measured during topical application of agonists and antagonists. Sphingosine (10(-6) M), a PKC inhibitor that binds to the regulatory site of PKC, attenuated vasoconstriction in response to endothelin (10(-9), 10(-8), and 10(-7) M) and vasopressin (10(-9) and 10(-8) M). H-7 (10(-9) M), a PKC inhibitor that binds to the catalytic site of PKC, also inhibited vasoconstriction in response to endothelin and vasopressin. Sphingosine and H-7 did not affect baseline diameter and did not attenuate vasoconstriction in response to prostaglandin (PG) F2 alpha. The V1 antagonist [d(CH2)5Tyr(Me)]arginine vasopressin (10(-8) M) significantly inhibited constriction in response to vasopressin (10(-9) and 10(-8) M) but not PGF2 alpha (10(-6) M). These observations suggest that activation of PKC may contribute to endothelin-induced constriction of the basilar artery in vivo and that PKC may also be a mediator of V1-receptor-mediated constriction of the basilar artery in response to vasopressin.

Sphingosine - pharmacology

Basilar Artery - drug effects

Animals

Isoquinolines - pharmacology

Endothelins - pharmacology

Rats

Male

Protein Kinase C - antagonists & inhibitors

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Arginine Vasopressin - pharmacology

Piperazines - pharmacology

Vasoconstriction - drug effects

Details

Title: Subtitle: Effect of protein kinase C inhibitors on endothelin- and vasopressin-induced constriction of the rat basilar artery
Creators: Margaret A Murray - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242
Frank M Faraci
Donald D Heistad
Resource Type: Journal article
Publication Details: The American journal of physiology, Vol.263(6 Pt 2), pp.H1643-H1649
DOI: 10.1152/ajpheart.1992.263.6.H1643
PMID: 1481891
NLM abbreviation: Am J Physiol
ISSN: 0002-9513
eISSN: 2163-5773
Publisher: United States
Grant note: HL-16066 / NHLBI NIH HHS NS-24621 / NINDS NIH HHS HL-14388 / NHLBI NIH HHS
Language: English
Date published: 12/1992
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040335002771

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