Effects of phorbol esters on canine coronary artery constriction and dilation in vitro

Frank M Sheridan; Lawrence D Horwitz; Ivan F McMurtry

doi:10.1152/ajpheart.1991.261.1.h236

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Effects of phorbol esters on canine coronary artery constriction and dilation in vitro

Journal article

Peer reviewed

Effects of phorbol esters on canine coronary artery constriction and dilation in vitro

Frank M Sheridan, Lawrence D Horwitz and Ivan F McMurtry

The American journal of physiology, Vol.261(1 Pt 2), pp.H236-H242

07/1991

DOI: 10.1152/ajpheart.1991.261.1.h236

PMID: 1858925

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Abstract

The influence of protein kinase C (PKC) activation on canine coronary vasoreactivity was assessed in vitro. Activation of PKC by phorbol 12,13-dibutyrate (PDBu) or phorbol 12-myristate 13-acetate (PMA) caused slow sustained constriction of isolated coronary artery rings. PDBu was a more potent and efficacious constrictor than PMA (169 +/- 21 vs. 81 +/- 7% of maximum KCl constriction). Constriction to PDBu was reduced slightly by deendothelialization and by meclofenamate. Pretreatment with threshold concentrations of PDBu increased constriction to serotonin from 3 +/- 1 to 48 +/- 4% of maximum KCl constriction whether or not the endothelium was present but had no effect on response to the thromboxane analogue U-46619. In addition, in arteries constricted with PDBu, dilations to ADP, thrombin, acetylcholine, and sodium nitroprusside were impaired when compared with arteries constricted with U-46619. These results suggest that activation of PKC in coronary arteries 1) produces potent constriction mediated only in small part by the endothelium and by cyclooxygenase products, 2) potentiates markedly the constrictor response to serotonin by an endothelium-independent mechanism, and 3) attenuates both endothelium-dependent and endothelium-independent vasodilation.

6-Ketoprostaglandin F1 alpha - metabolism

Animals

Coronary Circulation - drug effects

Culture Media

Dogs

Endothelium, Vascular - physiology

In Vitro Techniques

Meclofenamic Acid - pharmacology

Phorbol 12,13-Dibutyrate - pharmacology

Phorbol Esters - pharmacology

Serotonin - pharmacology

Vasoconstriction - drug effects

Vasodilator Agents - pharmacology

Details

Title: Subtitle: Effects of phorbol esters on canine coronary artery constriction and dilation in vitro
Creators: Frank M Sheridan - University of Colorado Health
Lawrence D Horwitz - University of Colorado Health
Ivan F McMurtry - University of Colorado Health
Resource Type: Journal article
Publication Details: The American journal of physiology, Vol.261(1 Pt 2), pp.H236-H242
DOI: 10.1152/ajpheart.1991.261.1.h236
PMID: 1858925
NLM abbreviation: Am J Physiol
ISSN: 0002-9513
eISSN: 2163-5773
Language: English
Date published: 07/1991
Academic Unit: Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984656540602771

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