Lack of endothelium-dependent relaxation in coronary resistance arteries of cholesterol-fed rabbits.
The endothelium-dependent contractile responses of subepicardial coronary resistance arteries (286 +/- 18 microns ID, n = 22) from rabbits fed either a 0.5 or 2.0% cholesterol-enriched diet or a control diet for 10-12 wk were determined under isometric conditions at the optimum length for active force production (Lo). After the development of tone with 29 mM K+-Krebs, arteries from control rabbits treated with acetylcholine (0.1-10 microM) showed a concentration-dependent relaxation, with a maximum decrease in tone of 63%. In contrast, coronary arteries from animals fed 0.5 and 2.0% cholesterol contracted to acetylcholine (approximately 210% increase in tone). A similar phenomenon was seen with arteries precontracted with 10 nM 9,11-methanoepoxy-prostaglandin H2 (U 46,619), a thromboxane A2 mimetic. The contractile responses to acetylcholine occurred in arteries in which the endothelium was structurally intact and which were devoid of plaque. Arteries from cholesterol-fed animals were poorly responsive to ADP (0.01-10.0 microM), whereas arteries from normal animals relaxed. All arteries relaxed to an equal degree when exposed to acidified nitrite, which produces nitric oxide (NO). The data suggest that as a result of hypercholesterolemia, there may be a dysfunction in the synthesis or release of endothelium-derived relaxing factor (EDRF) by the endothelial cells of coronary resistance arteries, rather than an abnormality of the smooth muscle cells per se.
Osborne
J A
JA
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Siegman
M J
MJ
Sedar
A W
AW
Mooers
S U
SU
Lefer
A M
AM
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D002791:Cholesterol, Dietary; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008854:Microscopy, Electron; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D012016:Reference Values
D002791:Cholesterol, Dietary; D000244:Adenosine Diphosphate; D000109:Acetylcholine