Mitochondrial ATP synthase regulation in heart: defects in hypertension are restored after treatment with captopril.
Control of mitochondrial ATP synthase capacity was investigated in cultured cardiomyocytes from normotensive (Wistar-Kyoto) and spontaneously hypertensive rats. Cells from spontaneously hypertensive rats have a higher basal ATP synthase capacity than those from normotensives, but lack the normal up-regulation in response to an increased energy demand. After treatment of spontaneously hypertensive rats with captopril (60 mg/kg per day for 12 weeks), cellular hypertrophy characteristic of the hypertensives was abolished and the cardiomyocytes showed a normal ATP synthase capacity. Normal up-regulation of this enzyme was also restored. All cells showed a normal down-regulation of the synthase in response to cyanide. Experiments with the calcium antagonists, verapamil and ruthenium red, suggest that abnormal ATP synthase regulation observed in the untreated spontaneously hypertensive rats results from an alteration of Ca2+ handling in cardiac cells under chronic high workload, which is reversed by captopril treatment.
D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004558:Electric Stimulation; D006973:Hypertension / Q000201:enzymology* / Q000473:pathology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012430:Ruthenium Red / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002316:Cardiotonic Agents; D009097:Multienzyme Complexes; D011719:Pyrazines; D012430:Ruthenium Red; C048350:5-(4-acetamidophenyl)pyrazin-2(1H)-one; D002216:Captopril; D014700:Verapamil; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D006180:Proton-Translocating ATPases; D007545:Isoproterenol