DESCRIPTION (provided by applicant): The exercise pressor reflex is widely believed to play an important rote in controlling the sympathetic outflow to the vasculature during exercise in both humans and animals. The reflex is believed to arise from contracting skeletal muscles and is evoked by two types of stimuli, namely mechanical and metabolic. The sensory arm of the exercise pressor reflex arc is comprised of group III and IV fibers, which together haw been termed thin fiber muscle afferents.. Group I and II fibers do not participate in evoking this reflex. Although the role played the exercise pressor reflex in increasing arterial blood pressure during exercis, is well established, its control of the sympathetic outflow to specific visceral and somatic structures controversial. This is especially the case for the role played by metaboreceptors in reflexly activating the sympathetic outflow to the vasculature of the skin. In addition, the specific roles played by thin fiber mechanoreceptors and metaboreceptors in activating the sympathetic outflow to the skeletal muscles and the kidney are unknown. The experiments proposed in this application will determine the effect of blocking the contractioninduced input from thin fiber muscle mechanoreceptors and metaboreceptors on the responses of single fiber sympathetic postganglionic efferent fibers innervating the vasculature of hind limb hairy skin, the vasculature of hind limb skeletal muscle and the kidney. Mechanoreceptor input arising from the triceps surae muscles of decerebrate unanesthetized cats will be prevented by popliteal arterial injections of gadolinium, an agent which blocks mechanogated channels. Metaboreceptor input from these muscles will be blocked by popliteal arterial injections of PPADS, a purinergic 2 receptor antagonist. The sympathetic nature of the efferent discharge will be identified by: 1.) showing that the efferents are activated by an electrical pulse applied to the thoracic or lumbar sympathetic chain;2.) showing that both spontaneous and evoked activity is prevented by ganglionic blockade with hexamethonium;and 3.) showing that the activity of the renal, muscle and to a lesser extent, skin sympathetic discharge is under control of the arterial baroreceptors. The proposed experiments will provide new information about the role played by thin fiber muscle mechanoreceptors and metaboreceptors in controlling the sympathetic outflow during exercise.
|Effective start/end date||7/1/04 → 3/31/11|
- National Institute of Arthritis and Musculoskeletal and Skin Diseases: $305,790.00
- National Institute of Arthritis and Musculoskeletal and Skin Diseases: $1.00
- National Institute of Arthritis and Musculoskeletal and Skin Diseases: $312,032.00
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