Evidence for increased in vivo Na(+)-H+ antiporter activity and an altered skeletal muscle contractile response in the spontaneously hypertensive rat.
We have assessed the in vivo activity of the Na(+)-H+ antiporter skeletal muscle in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) controls using phosphorus (31P) nuclear magnetic resonance spectroscopy to measure changes in cytosolic acid concentrations during isometric contraction. During contraction there was a small rate of rise in skeletal muscle cytosolic acid concentration to a smaller maximum concentration in SHR. This difference in acid response was removed by amiloride and was not attributable to differences in cell buffering or the rate of production of lactic acid, suggesting that the difference in acid response in SHR skeletal muscle is due to increased in vivo Na(+)-H+ antiporter activity. Amiloride reduced resting muscle glycogen concentration and increased muscle lactate concentration in the SHR. This could be related to altered in vivo calcium metabolism. The maximum tension produced by skeletal muscle during contraction in SHR was less than in WKY rats, and relaxation between twitches was significantly greater, consistent with the finding of increased vascular smooth muscle relaxation in essential hypertension. Since increased Na(+)-H+ antiporter activity occurs in association with increased relaxation of both skeletal and vascular smooth muscle, these data are not consistent with a relationship between increased Na(+)-H+ antiporter activity and increased maximal muscle tension development. However, they show that increase Na(+)-H+ antiporter activity is associated with increased muscle relaxation.
Syme
P D
PD
MRC Unit, Radcliffe Infirmary, Oxford, UK.
Arnolda
L
L
Green
Y
Y
Aronson
J K
JK
Grahame-Smith
D G
DG
Radda
G K
GK
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D007537:Isometric Contraction / Q000502:physiology*; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D007773:Lactates; D017923:Sodium-Hydrogen Exchangers; D019344:Lactic Acid; D000584:Amiloride; D006003:Glycogen