Decreased basal nitric oxide release in hypercholesterolemia increases neutrophil adherence to rabbit coronary artery endothelium.
Hypercholesterolemia, before atherosclerosis, is known to reduce agonist- (e.g., acetylcholine) mediated nitric oxide (NO) production within 2 weeks of a cholesterol-enriched diet. However, no data exist on the effect of hypercholesterolemia on the basal release of NO from blood vessels. We studied the basal release of NO in rabbit coronary arteries by addition of the NO synthase blocker NG-nitro-L-arginine-methyl ester (L-NAME). Basal release of NO was markedly attenuated 2 weeks after introduction of a 0.5% cholesterol addition to the diet. One week later, the adherence of neutrophils to the coronary endothelium was significantly enhanced (i.e., threefold; p < 0.01 different from control). The increased adhesiveness could be attributed to enhanced endothelial adhesion rather than to changes in the properties of the leukocytes. Both phenomena could be reversed by addition of L-arginine to isolated coronary arteries. Administration of 10 mg/day lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, markedly attenuated both the reduced basal NO production and the increased adhesiveness of the endothelium. These results support the concept that NO is an important protective agent produced by the endothelium to preserve the integrity of the endothelium and may protect it against atherogenesis.
Lefer
A M
AM
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa. 19107-6799.
Ma
X L
XL
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000494:pharmacology; D003331:Coronary Vessels; D004730:Endothelium, Vascular / Q000166:cytology*; D006937:Hypercholesterolemia / Q000378:metabolism*; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009504:Neutrophils / Q000166:cytology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D011817:Rabbits
D002791:Cholesterol, Dietary; D009569:Nitric Oxide; D001120:Arginine; D008148:Lovastatin; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester