Faculty Collaboration Database

Aortic thromboxane receptor deficiency alters vascular reactivity in cholesterol-fed rabbits. Atherosclerosis 2006 Dec;189(2):358-63

Date

03/07/2006

Pubmed ID

16515789

DOI

10.1016/j.atherosclerosis.2006.02.004

Scopus ID

2-s2.0-33750292018 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

Hypercholesterolemia is considered a major risk factor in the development of atherosclerotic disease. The endothelium is the source of a number of vasoactive compounds which may be altered by the disease process. For example, synthesis of the arachidonic acid metabolite thromboxane A(2) (TXA(2)) increases in atherosclerosis. Non-selective blockade of vascular and platelet thromboxane (TP) receptors retards the progression of the disease in various animal models. We have previously identified a subset of NZW rabbits that lack only vascular (v) TP receptors, referred to as vTP-. These rabbits provide a unique model to elucidate the role of vascular TP receptors in hypercholesterolemia. Studies evaluated vascular responses to phenylephrine and acetylcholine in isolated aortic rings obtained from vTP- and vTP+ rabbits fed 0.5% cholesterol diet for a period of only 3 weeks. In the cholesterol-fed vTP- rabbits, contractions to phenylephrine were reduced compared to the vTP+ cholesterol-fed rabbits. Acetylcholine-induced relaxations were greater in cholesterol-fed vTP- rabbits compared to cholesterol-fed vTP+ rabbits. While the overall incidence of aortic lesions was small after only 3 weeks of cholesterol-feeding, results indicated a reduction in lesions in the vTP- compared to the vTP+ rabbits. In summary, these studies are the first to show that if rabbits lack only vascular TP receptors, impaired vascular reactivity responses normally associated with hypercholesterolemia are diminished.

Author List

Pfister SL

Author

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

Acetylcholine
Animals
Aorta
Atherosclerosis
Cholesterol
Cholesterol, Dietary
Disease Models, Animal
Disease Progression
Hypercholesterolemia
Male
Rabbits
Receptors, Thromboxane
Vasoconstriction
Vasodilator Agents