Increased heart microsomal Na(+) K(+)-transporting ATPase activity by tetrandrine in spontaneously hypertensive rats.
In spontaneously hypertensive rats (SHR), the heart microsomal Na+, K(+)-ATPase showed a reduced activity with a higher Ca2+ sensitivity and lower responsiveness to K+. After SHR were treated with tetrandrine (Tet, ig 30 mg.kg-1, qd x 30 d) or when the microsomes obtained from SHR hearts were incubated with various concentrations of Tet, the myocardial Na+,K(+)-ATPase showed a higher activity with a decreased Km for K+, or ATP and an increased Vmax for K+. The in vitro stimulatory effect of Tet on the enzyme was dependent on the Na+ concentration in medium and was not abolished by CaCl2 1 mmol.L-1 or ouabain 0.1 mmol.L-1. However, when given in vivo, Tet tended to reduce the tolerance of the enzyme to Ca2+ and failed to change the responsiveness of the enzyme to ouabain. In vitro, Tet had similar but weaker stimulatory effect on the Na+,K(+)-ATPase from Wistar Kyoto rats.
Chen
N H
NH
Department of Pharmacology, Nanjing Medical College, China.
Wang
Y L
YL
Ding
J H
JH
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D044182:Benzylisoquinolines; D002122:Calcium Chloride / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology*; D008861:Microsomes / Q000201:enzymology; D008929:Mitochondria, Heart / Q000201:enzymology; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D000470:Alkaloids; D000959:Antihypertensive Agents; D044182:Benzylisoquinolines; C009438:tetrandrine; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D002122:Calcium Chloride