• Sinoway, Lawrence I. (PI)

Project: Research project

Project Details


The long range goal of the PI is to examine blood flow (0) regulation. This proposal investigates the role of sympathetic nervous system (SNS) in this process. Specifically, we are interested in how metaboreceptor stimulation in skeletal muscle alters SNS activity and Q delivery. Our hypotheses are that: 1) During exercise skeletal .muscle acidosis stimulates metaboreceptors and this increases sympathetic nervous system ,(SNS) activity. This process is crucial in regulating blood flow delivery to exercising !skeletal muscle. 2) Congestive heart failure (CHF) and exercise conditioning alter this response in opposite ways: for a given amount of work conditioning causes less acidosis ;and less metaboreceptor stimulation, CHF causes more acidosis and theoretically more metaboreceptor stimulation. However, it is postulated that both conditions via chronic stimulation can densensitize metaboreceptors. This proposal uses a number of models and methodologies to examine these hypotheses 1) simultaneous 3H-NE kinetics and microneurography (peroneal nerve, muscle sympathetic nerve activity, MSNA) will evaluate if the SNS response to forearm exercise is generalized and altered by training and CHF. 2) Measurements of MSNA and forearm Q (plethysmography) and 31p NMR spectroscopy of the exercising forearm are utilized to examine the relationship between SNS activation, forearm Q and metabolism during forearm exercise. These methods will also be used to examine the effects of training and CHF on this relationship- 3) The effects of (leg) metaboreceptor stimulation (post leg exercise circulatory arrest) to regulate peak (forearm) Q will be investigated under conditions that are designed to blunt (leg) muscle acid production (dichloroacetate and glycogen depletion). Vastas lateralis muscle biopsies will also be performed. 4) Post handgrip circulatory arrest will be used to evaluate the role of forearm skeletal muscle metaboreceptor stimulation on MSNA. 31p NMR will evaluate forearm high energy phosphate metabolism and pH and the ability of forearm glycogen depletion and dichloroacetate to alter the metaboreceptor response. The effects of training and CHF will also be evaluated. Finally, the concept that conditioning may blunt the metaboreceptor response by a densensitization process will be addressed using fatiguing handgrip exercise during circulatory arrest. These studies will provide insight into the mechanisms that control Q. The results of these experiments will help explain the improved exercise capacity with training and the reduced exercise capacity in heart failure.
Effective start/end date4/1/903/31/95


  • National Heart, Lung, and Blood Institute


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