Faculty Collaboration Database

Cooperative mediation by serotonin S2 and thromboxane A2/prostaglandin H2 receptor activation of cyclic flow variations in dogs with severe coronary artery stenoses. Circulation 1987 Oct;76(4):952-9

Date

10/01/1987

Pubmed ID

3652429

DOI

10.1161/01.cir.76.4.952

Scopus ID

2-s2.0-0023229589 (requires institutional sign-in at Scopus site)   87 Citations

Abstract

We have reported previously that thromboxane A2/prostaglandin (PG)H2 and serotonin independently mediate the occurrence of cyclic flow variations (CFVs) in a canine preparation of severe coronary artery narrowing. This may be due to an effect of these substances on platelets and/or the vascular wall. We tested the hypothesis that there is a cooperative effect between thromboxane A2/PGH2 and serotonin receptor stimulation in the development of CFVs in this animal preparation. After placement of a hard plastic cylindrical constrictor around the left anterior descending coronary artery, CFVs develop and are characterized by repetitive cycles of declines in coronary blood flow and abrupt increases in flow. In a control group of dogs, CFV frequency (cycles/hour) and severity (lowest coronary blood flow just before its restoration) did not change significantly over a 3 hr interval. In a second group of dogs, CFVs were established after constrictor placement, abolished with the serotonin (5HT2) receptor antagonist ketanserin, and reestablished by the continuous infusion of serotonin into the left atrium. Serotonin-induced CFVs were then abolished with a thromboxane A2/PGH2 receptor antagonist, SQ29,548, or a thromboxane synthetase inhibitor, dazoxiben (UK37,248). The relative specificity of the respective antagonists, SQ29,548 and ketanserin, was determined in canine platelets and rat aortic vascular strips. No significant cross-reactivity between ketanserin and SQ29,548 was found. Thus, the data obtained in these studies demonstrate a cooperative interaction between thromboxane A2/PGH2 and serotonin S2 receptors that contributes to the development of CFVs in this experimental preparation.

Author List

Ashton JH, Ogletree ML, Michel IM, Golino P, McNatt JM, Taylor AL, Raheja S, Schmitz J, Buja LM, Campbell WB

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Coronary Circulation
Coronary Disease
Dogs
Drug Antagonism
Epinephrine
Hemodynamics
In Vitro Techniques
Ketanserin
Male
Muscle Contraction
Muscle, Smooth, Vascular
Platelet Aggregation
Prostaglandin Endoperoxides
Prostaglandin Endoperoxides, Synthetic
Prostaglandin H2
Prostaglandins H
Rats
Receptors, Prostaglandin
Receptors, Serotonin
Thromboxane A2