INCREASED NA-K+ PUMP NUMBER AND DECREASED PUMP ACTIVITY IN SOLEUS MUSCLES IN SHR()

We have previously demonstrated electrophysiological and contractile a bnormalities in soleus muscles of the spontaneously hypertensive rat ( SHR). The age-related decrease in force and fatigue resistance observe d in SHR muscles may be produced by alterations in sarcolemmal ion con ductance and/or Na+ pump function. The experiments reported in the pre sent paper were designed to assess the functional capacity of the Napump in 6- to 8- and 24- to 28-wk-old SHR and Wistar-Kyoto (WKY) soleu s muscles and to correlate pump activity with Na+ pump number and bind ing affinity ([H-3]ouabain binding). Functional capacity was determine d by measuring the change in resting membrane potential (RMP) of soleu s muscle fibers in response to agents that stimulate (epinephrine and insulin) or inhibit (ouabain) the pump and by measuring maximum ouabai n-suppressible Rb-86(+) uptake in Na+-loaded muscles. Na+ pump number and affinity were quantified by determining the specfic binding of [H- 3]ouabain in soleus muscle slices. SHR soleus muscles contain a greate r number of Na+ pump sites (ouabain binding sites) than are present in age-matched WKY muscles but also experience a significant decrease in pump activity with age. SHR may upregulate pump number in response to the significantly higher intracellular Na+ concentration found in sol eus muscles at all the ages examined. The apparent reduction in pump c apacity with age may play a major role in the observed age-related dec rease in SHR soleus force and fatigue resistance.