title: Ageing is associated with impairment of nitric oxide and prostanoid dilator pathways in the human forearm.
abstract: Ageing is associated with endothelial dysfunction and increased cardiovascular risk. We assessed the activity of nitric oxide (NO) and prostaglandin pathways in older subjects. Bilateral venous occlusion plethysmography was used to measure forearm blood flow during intra-arterial infusion of the NO synthase inhibitor, N(G)-monomethyl--arginine (-NMMA; 1, 2 and 4 micromol/min), the cyclo-oxygenase inhibitor, aspirin (3, 9 and 30 micromol/min), and the smooth muscle constrictor, noradrenaline (60, 120 and 240 pmol/min); each dose infused for 5 min. Eighteen young and 15 healthy older subjects (mean age+/-S.E.M., 32+/-1 and 65+/-1 years respectively) were studied. Effects of treatment were calculated from the ratio of blood flow in the infused to control arm, expressed as a percentage. Dose-response curves were compared by analysis of the area under the curve (AUC) using independent samples t test. All agents caused dose-dependent decreases in basal forearm blood flow. AUC values for noradrenaline, aspirin and -NMMA in younger and older subjects were 162+/-24, 173+/-24 and 170+/-17, and 138+/-22, 70+/-22 and 89+/-22 respectively. Effects of aspirin and -NMMA, but not noradrenaline, were reduced in older subjects (P=0.004, 0.007 and 0.461 respectively). Our findings suggest a generalized abnormality of basal endothelial function in older people, with similar impairment of NO and prostanoid dilator pathways. Defects in both pathways could contribute to the development of age-related cardiovascular disease.
authors: Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. nsingh@sghms.ac.uk
authors: Nivedita
authors: N
authors: Singh
authors: Sanjay
authors: S
authors: Prasad
authors: Donald R J
authors: DR
authors: Singer
authors: Raymond J
authors: RJ
authors: MacAllister
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D001241:Aspirin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D010991:Plethysmography; D011453:Prostaglandins / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D001241:Aspirin; D009638:Norepinephrine