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.
