EFFECT OF CHRONIC BLOOD-PRESSURE REDUCTION ON SOLEUS MUSCLE CONTRACTILE PROPERTIES IN SPONTANEOUSLY HYPERTENSIVE RATS

Soleus muscle in Wistar-Kyoto rats (WKY), as well as in most normotens ive mammals, is highly fatigue resistant. In 6-mo-old spontaneously hy pertensive rats (SHR), however, soleus muscle generates less specific force and experiences a more rapid rate of fatigue than in age-matched WKY. The present experiments tested the hypothesis that antihypertens ive treatment with hydralazine or amlodipine would shift the contracti le force and fatigue resistance profile of SHR soleus toward that whic h characterizes WKY. Hydralazine was given via the drinking water (100 mg/l) and amlodipine via the food (1 g/4 kg rat chow) to two separate groups of animals, starting at the age of 16 wk. At 24-26 wk of age s oleus twitch and tetanic force generation and the rate of fatigue were evaluated during a 4-min period of repetitive stimulation. Although b oth hydralazine and amlodipine lowered blood pressure, they had differ ent effects on muscle function. Hydralazine decreased force generation in both WKY and SHR at all stimulation frequencies; it did not change the fatigue properties of SHR but made WKY soleus less fatigue resist ant. Amlodipine, on the other hand, increased contractile force in bot h WKY and SHR and increased fatigue resistance in SHR. Amlodipine is a dihydropyridine that blocks L-type channels, thereby preventing entry of Ca2+ into the muscle. We suggest that Ca2+ entry during activity s timulates Ca-activated Kf efflux in SHR and adds to the extracellular load of K+. Increased extracellular K+ can in turn depress contractile performance.