Faculty Collaboration Database

Augmented vasoconstrictor responses to serotonin precede development of atherosclerosis in aorta of WHHL rabbit. Arteriosclerosis 1989;9(2):195-202

Date

03/01/1989

Pubmed ID

2647071

DOI

10.1161/01.atv.9.2.195

Scopus ID

2-s2.0-0024510564 (requires institutional sign-in at Scopus site)   56 Citations

Abstract

Watanabe heritable hyperlipidemic (WHHL) rabbits have elevated concentrations of plasma cholesterol and develop progressive atherosclerosis. The present investigation was undertaken to evaluate the vascular responses to vasoactive compounds of aorta from WHHL rabbits and normal New Zealand White (NZW) rabbits at 1 and 6 months of age. Rings of distal thoracic aorta were suspended under isometric tension in oxygenated Krebs buffer. Developed tension was measured in response to graded concentrations of agonists. Maximal responses to KCl (40 mM) were the same in aortas from the 1-month-old and 6-month-old WHHL and NZW rabbits. Aortas from 1-month-old animals were more sensitive to serotonin than aortas from 6-month-old animals. Aortas from WHHL rabbits exhibited an increased maximal response to serotonin when compared with NZW controls. In contrast, the constrictor responses to norepinephrine were reduced in WHHL rabbits compared with NZW rabbits at both age groups. Methacholine decreased tension development in serotonin-contracted vessels. This relaxation was greatest in aortas from NZW rabbits. In 1-month-old NZW rabbits fed a high cholesterol diet, the constrictor responses to serotonin and the relaxation responses to methacholine did not differ from NZW rabbits ingesting a normal diet. However, the responses to norepinephrine were markedly attenuated in the hypercholesterolemic NZW rabbits. Microscopic evaluation of the aortas revealed occasional adherent leukocytes and irregularities in the vascular endothelium in 1-month-old WHHL animals. These changes were greater in aortas from 6-month-old WHHL animals, with more adherent leukocytes, adherent platelets, and severe irregularities in the endothelial surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Author List

Wines PA, Schmitz JM, Pfister SL, Clubb FJ Jr, Buja LM, Willerson JT, Campbell WB

Authors

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

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

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Animals
Aorta
Aortic Diseases
Arteriosclerosis
Cholesterol, Dietary
Histamine
Hyperlipidemias
In Vitro Techniques
Methacholine Chloride
Methacholine Compounds
Norepinephrine
Prostaglandin Endoperoxides, Synthetic
Rabbits
Serotonin
Vasoconstriction