Effects of antihypertensive therapy on cardiac sodium/hydrogen ion exchanger activity and hypertrophy in spontaneously hypertensive rats.
BACKGROUND
Sodium/hydrogen ion exchange is hyperactive in hypertension. Myocardial sodium/hydrogen ion exchange hyperactivity accompanies the regression of cardiac hypertrophy in spontaneously hypertensive rats (SHR) after long term control of blood pressure with enalapril.


OBJECTIVE
To explore whether this effect is shared by other antihypertensive agents or is specific to angiotensin-converting enzyme inhibition.


METHODS
SHR and normotensive Wistar Kyoto (WKY) rats were treated for five weeks with enalapril (20 mg/kg/day), nifedipine (10 mg/kg/day) or losartan (40 mg/kg/day). Sodium/hydrogen ion exchange activity was estimated in terms of both steady intracellular pH in HEPES buffer and the rate of intracellular pH recovery from intracellular acid loads in isolated superfused 2'-7'-bis(2-carboxyethyl)-5,-(and-6)-carboxyfluorescein, acetoxymethyl ester form-loaded papillary muscles.


RESULTS
Enalapril, nifedipine and losartan decreased systolic blood pressure in SHR to about the same value (140 3, 140 2 and 146 3 mmHg, respectively, at the end the treatment). However, the index of cardiac hypertrophy (heart weight to body weight ratio) was decreased to a smaller value with losartan than with nifedipine or enalapril (2.66 0.09, 3.06 0.05 and 2.86 0.04 mg/g respectively; P<0.05 ANOVA). For the untreated SHR, the index of cardiac hypertrophy was 3.30 0.04 mg/g. Myocardial sodium/hydrogen ion exchange hyperactivity in SHR was normalized by all treatments.


CONCLUSIONS
The three treatments regressed cardiac hypertrophy and normalized sodium/hydrogen ion exchange exchange activity in SHR, and losartan was the most effective treatment for reversing cardiac hypertrophy, despite producing effects on blood pressure and sodium/hydrogen exchange activity similar to that of other antihypertensive drugs.
Alvarez
Bernardo V
BV
Universidad Nacional de La Plata, La Plata, Argentina.
Ennis
Irene L
IL
De Hurtado
María C Camilión
MC
Cingolani
Horacio E
HE
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D006332:Cardiomegaly / Q000378:metabolism; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy*; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects*
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D017923:Sodium-Hydrogen Exchangers; D004656:Enalapril; D009543:Nifedipine; D019808:Losartan