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 normotensive mammals, is highly fatigue resistant. In 6-mo-old spontaneously hypertensive 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 antihypertensive treatment with hydralazine or amlodipine would shift the contractile force and fatigue resistance profile of SHR soleus toward that which 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 soleus twitch and tetanic force generation and the rate of fatigue were evaluated during a 4-min period of repetitive stimulation. Although both hydralazine and amlodipine lowered blood pressure, they had different 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 resistant. Amlodipine, on the other hand, increased contractile force in both 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 stimulates Ca-activated K+ efflux in SHR and adds to the extracellular load of K+. Increased extracellular K+ can in turn depress contractile performance.
Gray
S D
SD
Department of Human Physiology, School of Medicine, University of California, Davis 95616.
Carlsen
R C
RC
Atherley
R
R
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006614:Hindlimb; D006830:Hydralazine / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D017311:Amlodipine; D006830:Hydralazine