Evidence suggests that flow dependent vasodilation is mediated in part by the local activation and activity of vascular nitric oxide (NO) released from the endothelium. Flow mediated NO release is thought to be mediated through the action of shear stress on the vascular endothelium. Pulsatile shear stress i believed to be most effective in releasing NO. Exercise is probably the most physiologically normal cause of increased blood flow. Chronic exercise conditioning is accompanied by structural remodelling of the vascular wall and enhanced synthesis of ENOS the endothelial NO synthase. The relationships between pulsatile flow, NO release, structural remodelling and arterial wall function in vivo are largely unknown.
The specific aims of the research proposal are to determine the relaxation between NO release and pulsatile flow and between NO release and vascular elastic properties in the sedentary dog, with brief exercise training and with chronic exercise conditioning, and to measure changes in epicardial coronary artery size, morphology and ENOS activity with chronic exercise conditioning. For this purpose mongrel dogs will be employed. Dogs will be instrumented to measure circumflex coronary artery diameter and flow, and arterial and left ventricular pressure. Epicardial pacing electrodes and coronary artery occludes will be used. Dogs will be trained to lie on a lab table and to run on a treadmill. Coronary shear-stress and diameter will be altered acutely using pacing, acute exercise, reactive hyperemia, isoproterenol, nitroglycerin, and acetylcholine. Some dogs will undergo chronic exercise conditioning and measurements repeated. The relation between pulsatile shear stress and NO release will be quantitated. Changes in arterial wall elastic properties will be measured, and coronary artery wall histology and morphometrics will be performed. ENOS activity will be assessed via Northern blot analysis.
| Stewart, J M; Gewitz, M H; Weldon, A et al. (1999) Patterns of orthostatic intolerance: the orthostatic tachycardia syndrome and adolescent chronic fatigue. J Pediatr 135:218-25 |
| Stewart, J M; Xu, X; Ochoa, M et al. (1998) Exercise reduces epicardial coronary artery wall stiffness: roles of cGMP and cAMP. Med Sci Sports Exerc 30:220-8 |
