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
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute


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