NA-PUMP ACTIVITY AND SKELETAL-MUSCLE CONTRACTILE DEFICITS IN THE SPONTANEOUSLY HYPERTENSIVE RAT(, K+)

Skeletal muscles in an animal model of generic hypertension (the spont aneously hypertensive rat. SHR) exhibit significant deficits in contra ctile performance. These deficits appear to be unrelated to the rise i n blood pressure. Slow-twitch soleus muscles show a decrease in specif ic muscle tension and a reduced resistance to muscle fatigue during pr olonged contractile activity. We rested the hypothesis that the reduce d fatigue resistance occurs as a consequence of an impaired ability to maintain or restore Na+ and K+ balance across the sarcolemma during r epeated contractions. This may result from a genetically based increas e in the Na+ permeability of SHR muscles, coupled with a reduction Na. K+ pump capacity as the animals mature. Soleus muscles in adult SHR exhibit a significant increase in intracellular Na+ content and a sign ificant decrease in intracellular K+ content at rest. Rb-86(+) uptake in Na+-loaded hypertensive muscles is 45% less than predicted from the number of ouabain-binding sites available. Activation of Na+, K+ pump s using adrenaline or insulin produces a significantly smaller hyperpo larization in hypertensive soleus than in control muscles. Control sol eus muscles are hyperpolarized for at least 10 min after a 4 min perio d of high-frequency activity. but hypertensive soleus muscles remain a t resting polarity. Nonetheless. the number of ouabain-binding sites i n hypertensive muscles is significantly greater than in control soleus , and binding affinities are similar. This apparent deficit in pump ca pacity might lead to a greater and more prolonged increase in extracel lular K+ during repetitive contractions, and an associated decline in tension. Recently. we have been able to prevent the abnormal decrease in hypertensive soleus fatigue resistance by long-term treatment (8 we eks) with the Ca2+ blocker amlodipine. The therapy prevented or revers ed the contractile deficits, but did not restore the responsiveness of the Na+, K+ pump to hormonal stimulation. The current data suggest th at both a reduction in Na+, K+-pump capacity and changes in Ca2+ distr ibution play a role in the development of contractile deficits in hype rtensive muscles.