Role of the endothelium in the genesis of cardiovascular disease.
1. Endothelial cells release nitric oxide (NO) and the putative endothelium-derived hyperpolarizing factor (EDHF) in response to an increase in shear stress and receptor stimulation. 2. Tests of endothelial function have principally used acetylcholine (ACh)-mediated relaxation of precontracted isolated blood vessels or increases in forearm blood flow measured by venous occlusion plethysmography. Basal NO release is tested by a rise in resistance during infusion of the NO synthase inhibitor L-NMMA. Potential traps for investigators looking to evoke endothelial dysfunction following reduced ACh responses are discussed. 3. Endothelial dysfunction appears to occur in large but not small arteries in human and animal hypertension. Patients with long-standing congestive heart failure have endothelial dysfunction in buttock skin resistance arteries and there is coronary artery endothelial dysfunction following coronary ischaemia. 4. Remodelled arteries from neointimal thickening as a result of coronary collateral development in dog heart and new angiogenic vessel growth following large artery occlusion in the rabbit hindlimb appear to have normal endothelial function in relation to NO release. 5. Development of specific NO synthase inhibitors, antagonists of EDHF and the constrictor peptide endothelin, will clarify the role of these endothelium-derived factors in the cause or maintenance of vascular dysfunction. Defining redundancy and hierarchy of importance of these vascular factors are areas for future resolution.
Angus
J A
JA
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D011817:Rabbits