Regression of cardiomyocyte hypertrophy in SHR following chronic inhibition of the Na(+)/H(+) exchanger.
OBJECTIVE
Experiments were performed to examine the effect of chronic inhibition of the Na(+)/H(+) exchanger isoform-1 (NHE-1) on cardiac hypertrophy of spontaneously hypertensive rats (SHR).


METHODS
SHR were orally treated during 1 month with two different doses (0.3 and 3.0 mg/kg/day) of the NHE-1 inhibitor, cariporide, or nifedipine (10.0 mg/kg/day).


RESULTS
The two doses of cariporide did not differ in their effects after 1 month of treatment, since both induced a slight decrease in systolic blood pressure (SBP) of approximately 6 mmHg and regression of the heart weight to body weight ratio (mg/g) from 3.28+/-0.05 to 3.04+/-0.05 (0.3 mg) and 2.99+/-0.10 (3.0 mg, P<0.05). Nifedipine, given for the same period, produced similar reduction in the hypertrophy index (3.03+/-0.05), but with a much greater decrease in arterial pressure (35.6+/-7.4 mmHg). Chronic treatment with cariporide induced a complete regression of the augmented cross sectional area of left ventricular myocytes without significant changes in collagen content, serum procollagen 1 propeptide levels or myocardial distensibility.


CONCLUSIONS
NHE inhibition represents a novel approach to induce regression of pathological hypertrophy of the heart. The finding can be rationalized mechanistically by previous in vitro studies suggesting a role of the NHE in the development of myocardial hypertrophy.
Camilión de Hurtado
María C
MC
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, 60 y 120 (1900) La Plata, Argentina. cicme@infovia.com.ar
Portiansky
Enrique L
EL
Pérez
Néstor G
NG
Rebolledo
Oscar R
OR
Cingolani
Horacio E
HE
D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D006332:Cardiomegaly / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D024042:Collagen Type I / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006146:Guanidines / Q000627:therapeutic use*; D006973:Hypertension / Q000097:blood; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000502:physiology; D013450:Sulfones / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D024042:Collagen Type I; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide