Aortic thromboxane receptor deficiency alters vascular reactivity in cholesterol-fed rabbits.
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.
Pfister
Sandra L
SL
Department of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. spfister@mcw.edu
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000493:pharmacokinetics / Q000633:toxicity; D004195:Disease Models, Animal; D018450:Disease Progression; D006937:Hypercholesterolemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000172:deficiency*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D002791:Cholesterol, Dietary; D017482:Receptors, Thromboxane; D014665:Vasodilator Agents; D002784:Cholesterol; D000109:Acetylcholine