Preliminary experiments from our laboratories suggest that prolonged, untreated hypertension in Spontaneously Hypertensive Rats (SHR) leads to a decrease in the size, strength, and endurance of skeletal muscles. Despite the potential significance of these effects to patient motor capacity, electrolyte homeostasis, and the side effects of antihypertensive therapy little attention has been paid to skeletal muscle function in hypertensive patients or animals. Most investigations of skeletal muscle properties influenced by hypertension have been concerned with blood supply and changes in fiber type. This proposal is intended to extend our preliminary data and investigate the ontological progress of muscle dysfunction in hypertensive rats, the possible bases for functional defects, and their susceptibility to antihypertensive therapy. The proposed project will initially establish a data base describing the structural and functional changes which appear in specific muscle types in genetically and experimentally-induced hypertensive rats. Measurements will include the electrical and mechanical properties of muscles in situ, and the structure and metabolic capacity of excised muscles. Several experimental objectives will be pursued: a) To distinguish muscle defects induced by hypertension per se, and describe their development and progression; b) To determine the effect of different antihypertensive therapies on the recovery of muscle function; c) To explore possible causal bases for the appearance of muscle defects by investigating muscle electrolyte balance and adrenergic receptor activity. This study will provide new information in two areas. First, it offers a new approach to the investigation of skeletal muscle plasticity and the short- and long-term consequences of antihypertensive therapies, such as the use of Beta blockers. Second, skeletal muscle preparations offer advantages to the investigation of hypertension-induced molecular defects in excitable cells which may also affect cardiac and smooth muscle. The size, relative homogeneity and variety of experimental approaches available with skeletal muscle make it well suited for the study of changes induced by systemic disease.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cardiovascular and Pulmonary Research B Study Section (CVB)
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University of California Davis
Schools of Medicine
United States
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Vali, S; Carlsen, R; Pessah, I et al. (2000) Role of the sarcoplasmic reticulum in regulating the activity-dependent expression of the glycogen phosphorylase gene in contractile skeletal muscle cells. J Cell Physiol 185:184-99
Matthews, C C; Carlsen, R C; Froman, B et al. (1998) Nerve-dependent factors regulating transcript levels of glycogen phosphorylase in skeletal muscle. Cell Mol Neurobiol 18:319-38
Carlsen, R C; Kerlin, D; Gray, S D (1996) Regeneration and revascularization of a nerve-intact skeletal muscle graft in the spontaneously hypertensive rat. Am J Physiol 270:R153-61
Atrakchi, A; Gray, S D; Carlsen, R C (1994) Development of soleus muscles in SHR: relationship of muscle deficits to rise in blood pressure. Am J Physiol 267:C827-35
Pickar, J G; Carlsen, R C; Atrakchi, A et al. (1994) Increased Na(+)-K+ pump number and decreased pump activity in soleus muscles in SHR. Am J Physiol 267:C836-44
Pickar, J G; Gray, S D; Carlsen, R C (1992) Appearance of alpha 1-adrenergic receptors in soleus muscles from SHR. Am J Physiol 262:C1284-91
Pickar, J G; Atrakchi, A; Gray, S D et al. (1991) Apparent upregulation of Na+,K+ pump sites in SHR skeletal muscle with reduced transport capacity. Clin Exp Hypertens A 13:645-52
Atrakchi, A; Carlsen, R C; Gray, S D et al. (1989) Beta-receptor properties in soleus muscles from spontaneously hypertensive rats. Hypertension 14:54-60