© 2000 American Heart Association, Inc.
Vascular Biology |
Peripheral Vascular Endothelial Dysfunction and Apoptosis in Old Monkeys
From The Weis Center for Research (K.A., R.K.K., Y.-T.S., G.-P.Y, G.T., A.B.K., N.S., D.E.V., S.P.B., S.F.V.), Pennsylvania State University, College of Medicine, Danville; the Cardiovascular and Pulmonary Research Institute (Y.-J.G.), Allegheny University of the Health Sciences, Pittsburgh, Pa; Simian Conservation Breeding & Research Center Inc (J.B.N.), Makati, Philippines; and the Research and Biotechnology Division (F.N.), St. Luke’s Medical Center, Quezon City, Philippines.
Correspondence to Stephen F. Vatner, MD, Director of the Henry Hood Research Program, Charles B. Degenstein Professor, Sigfried and Janet Weis Center for Research, Pennsylvania State University, College of Medicine, 100 N Academy Ave, Danville, PA 17822-2601. E-mail svatner{at}psghs.edu
Abstract—To determine the effects of aging on vasoactivity in a primate model (Macaca fascicularis), 13 young male monkeys (aged 7.1±0.4 years) and 9 old male monkeys (aged 19.8±0.6 years) were chronically instrumented for measurement of left ventricular and aortic pressures and cardiac output. Total cholesterol, triglyceride, and fasting blood sugar levels were not different between the 2 groups. There were no significant differences in baseline mean aortic pressure and total peripheral resistance (TPR) in the young monkeys versus the old monkeys. TPR fell less (P<0.05) with acetylcholine (1 µg/kg) in old monkeys (-25±1%) than in young monkeys (-34±2%), whereas decreases in TPR with sodium nitroprusside were similar in old and young monkeys. There was no evidence of atherosclerosis, but apoptosis of endothelial cells was enhanced (P<0.05) in the aortas and femoral arteries, but not in the media, of the old monkeys. There was a relationship (r=0.62, P=0.013) between the incidence of terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling (TUNEL)-positive endothelial cells and endothelial cell density in the femoral artery. The reduced endothelial cell density was also correlated (r=0.82, P<0.01) with depressed TPR responses to acetylcholine. Thus, vascular endothelial dysfunction was present in old monkeys without evidence of atherosclerosis, which may be due to endothelial apoptosis and reduced endothelial cell density.
Key Words: aging • endothelium-dependent vasodilation • apoptosis • vascular endothelial cell density
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