From the Centro de Investigaciones Cardiovasculares, Facultad de Ciencias
Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
Correspondence to Dr Horacio E. Cingolani, Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Calle 60 y 120, 1900 La Plata, Argentina. E-mail cicme{at}isis.unlp.edu.ar
Abstract—Intracellular pH is under
strict control in myocardium; H+ are extruded
from the cells by sodium-dependent mechanisms, mainly
Na+/H+ exchanger and
Na+/HCO3- symport, whereas
Na+-independent
Cl-/HCO3- exchanger extrudes
bases on intracellular alkalinization. Hypertrophic
myocardium from spontaneously hypertensive rats (SHR)
exhibits increased Na+/H+ exchange activity
that is accompanied by enhanced extrusion of bases through
Na+-independent
Cl-/HCO3- exchange. The
present experiments were designed to investigate the effect of
enalapril-induced regression of cardiac hypertrophy on the
activity of these exchangers. Male SHR and normotensive Wistar-Kyoto
rats (WKY) received enalapril maleate (20 mg/kg per day) in the
drinking water for 5 weeks. Gender- and age-matched SHR and WKY were
used as untreated controls. Enalapril treatment significantly reduced
systolic blood pressure in SHR and completely regressed cardiac
hypertrophy. Na+/H+ activity was
estimated in terms of both steady pHi value in HEPES buffer
and the rate of pHi recovery from CO2-induced
acid load. Na+-independent
Cl-/HCO3- activity was assessed
by measuring the rate of pHi recovery from intracellular
alkalinization produced by trimethylamine exposure. Regression of
cardiac hypertrophy was accompanied by normalization of
Na+/H+ and Na+-independent
Cl-/HCO3- exchange activities.
Inhibition of protein kinase C (PKC) activity with chelerythrine
(10 mmol/L) or calphostin C (50 nmol/L) returned both exchange
activities to normal values. These results show that
angiotensin-converting enzyme inhibition normalizes the
enhanced activity of both exchangers while regressing cardiac
hypertrophy. Because normalization of exchange activities
could be also achieved by PKC inhibition, the data would suggest that
PKC-dependent mechanisms play a significant role in the increased ion
exchange activities of hypertrophic myocardium and in their
normalization by angiotensin-converting enzyme
inhibition.
© 1998 American Heart Association, Inc.
Scientific Contributions
Enalapril Induces Regression of Cardiac Hypertrophy and Normalization of pHi Regulatory Mechanisms
Key Words: ion transport • hypertrophy, cardiac • angiotensin-converting enzyme inhibitors • protein kinase C • intracellular pH
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