Angiotensin-converting enzyme inhibition, intracellular Na+, and Na(+)-K+ pumping in cardiac myocytes.
Angiotensin-converting enzyme (ACE) inhibitors can reduce cardiac mass in both clinical and experimental cardiac hypertrophy. Because cytoplasmic Na+ and pH have been implicated as regulators of cell growth, we examined the effect of treatment with an ACE inhibitor on intracellular Na+ activity (alpha iNa) and pH (pHi) in the heart. After treatment of rabbits with captopril for 8 days alpha iNa was reduced relative to controls (3.6 +/- 0.4, n = 8, vs. 8.2 +/- 0.4 mM, n = 9, P < 0.001), whereas pHi was unchanged. To account for the difference in alpha iNa we measured electrogenic Na(+)-K+ pump activity in single isolated myocytes. Treatment with captopril increased pump currents at near-physiological levels of intracellular Na+ but had no effect at near-saturating levels of Na+. A similar increase in Na(+)-K+ pump activity occurred in rabbits treated with another ACE inhibitor, enalapril, but not with the vasodilator, hydralazine. We speculate that a decrease in alpha iNa after treatment with captopril may contribute to the well-documented ability of ACE inhibitors to reduce cardiac mass.
Hool
L C
LC
Department of Cardiology, Royal North Shore Hospital, St. Leonards, Australia.
Whalley
D W
DW
Doohan
M M
MM
Rasmussen
H H
HH
D000200:Action Potentials; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006830:Hydralazine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D012508:Sarcolemma / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D006830:Hydralazine; D004656:Enalapril; D002216:Captopril; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase