Na+, K(+)-pump activity and skeletal muscle contractile deficits in the spontaneously hypertensive rat

Skeletal muscles in an animal model of genetic hypertension (the spontaneously hypertensive rat. SHR) exhibit significant deficits in contractile performance. These deficits appear to be unrelated to the rise in blood pressure. Slow-twitch soleus muscles show a decrease in specific muscle tension and a reduced resistance to muscle fatigue during prolonged contractile activity. We tested the hypothesis that the reduced fatigue resistance occurs as a consequence of an impaired ability to maintain or restore Na+ and K+ balance across the sarcolemma during repeated contractions. This may result from a genetically based increase 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 significant decrease in intracellular K+ content at rest. B6RB+ uptake in Na(+)-loaded hypertensive muscles is 45% less than predicted from the number of ouabain-binding sites available. Activation of Na+, K+ pumps using adrenaline or insulin produces a significantly smaller hyperpolarization in hypertensive soleus than in control muscles. Control soleus muscles are hyperpolarized for at least 10 min after a 4 min period of high-frequency activity, but hypertensive soleus muscles remain at resting polarity. Nonetheless, the number of ouabain-binding sites in hypertensive muscle is significantly greater than in control soleus, and binding affinities are similar. This apparent deficit in pump capacity might lead to a greater and more prolonged increase in extracellular 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 weeks) with the Ca2+ blocker amlodipine. The therapy prevented or reversed the contractile deficits, but did not restore the responsiveness of the Na+, K+ pump to hormonal stimulation. The current data suggest that both a reduction in Na+, K(+)-pump capacity and changes in Ca2+ distribution play a role in the development of contractile deficits in hypertensive muscles.