Previous studies under this grant indicate that an alpha-constrictor tone limits myocardial perfusion and as a result imposes a limitation on myocardial contractile function. Because of the potential importance of this adrenergic effect on coronary perfusion and myocardial function during physical exertion in the human, four new studies are proposed. Research studies by others suggest that the alpha-constriction is mediated by circulating catecholamines rather than to neural mechanisms, while pilot studies from this laboratory indicate that neural mechanisms play a large role. Therefore, Study 5 will examine whether the coronary alpha- constrictor tone is mediated primarily humoral or by neural mechanisms. Studies also conflict with regard to the transmural distribution of an alpha-constrictor tone and its physiological importance in modulating myocardial blood flow. Study 6 will examine the transmural nature of he adrenergic constrictor tone and its effect on transmural myocardial function during exercise. Studies by others have shown that during progressive coronary occlusion, there is a reduction in flow leading to a reduction in contractile function long before the coronary dilatory reserve capacity is exhausted. Study 7 will examine whether the alpha-constrictor tone varies with the intensity of exercise, and whether the constrictor tone, as a result of restricting coronary flow also imposes a limitation on maximal cardiac performance at maximal levels of exercise. The specific alpha-receptor subtypes involved will also be examined. Pilot studies indicate that holding flow constant during mild exercise induces a sympathetic vasoconstriction. Therefore, Study 8 will examine whether ischemia during exercise elicits a neural reflex which imposes a coronary alpha-constriction. These important studies will be applicable to the treatment of the human with pre-existing coronary artery disease, especially during exertion.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034172-06
Application #
3346860
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1990-07-01
Project End
1994-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of North Texas
Department
Type
Schools of Osteopathy
DUNS #
110091808
City
Fort Worth
State
TX
Country
United States
Zip Code
76107
Stuewe, S R; Gwirtz, P A; Mallet, R T (2001) Exercise training increases creatine kinase capacity in canine myocardium. Med Sci Sports Exerc 33:92-8
Stuewe, S R; Gwirtz, P A; Agarwal, N et al. (2000) Exercise training enhances glycolytic and oxidative enzymes in canine ventricular myocardium. J Mol Cell Cardiol 32:903-13
Barron, B A; Laughlin, M H; Gwirtz, P A (1997) Exercise effect on canine and miniswine cardiac catecholamines and enkephalins. Med Sci Sports Exerc 29:1338-43
Dodd-o, J M; Gwirtz, P A (1996) Coronary alpha 1-adrenergic constrictor tone varies with intensity of exercise. Med Sci Sports Exerc 28:62-71
Kim, S J; Kline, G; Gwirtz, P A (1996) Limitation of cardiac output by a coronary alpha 1-constrictor tone during exercise in dogs. Am J Physiol 271:H1125-31
Gwirtz, P A (1995) Coronary alpha 1-constrictor tone during renovascular hypertension. Circulation 92:1576-81
Quist, E E; Lee, S C; Vasan, R et al. (1994) Chronic sympathectomy of canine cardiac ventricles affects Gs-adenylyl cyclase coupling and muscarinic receptor density. J Cardiovasc Pharmacol 23:936-43
Brandt, M A; Jones, C E; Gwirtz, P A (1993) Augmented coronary blood flow response to intracoronary norepinephrine after ventricular sympathectomy. Coron Artery Dis 4:101-7
Dodd-o, J M; Gwirtz, P A (1992) Cardiac response to acute coronary artery occlusion in exercise-trained dogs. Med Sci Sports Exerc 24:1245-51
Gwirtz, P A; Dodd-O, J M; Downey, H F et al. (1992) Effects of a coronary alpha 1-constriction on transmural left ventricular flow and contractile function. Am J Physiol 262:H965-72

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