Cardiac effects of amiloride and of enalapril in the spontaneously hypertensive rat.
OBJECTIVE
To compare the effects of the sodium-hydrogen exchange blocker, amiloride, with those of the angiotensin-converting enzyme inhibitor, enalapril, on cardiac structure and function and intracardiomyocyte calcium concentration ([Ca2+]i) and pH (pHi), in spontaneously hypertensive rats (SHRs).


METHODS
Experiments were performed in SHRs treated for 4 weeks with amiloride 7.5 mg/kg per day, enalapril 6.0 mg/kg per day or vehicle, and in Sprague-Dawley rats (SDRs). After haemodynamic measurements were taken, the heart was removed and weighed and hydroxyproline (a marker of collagen content) was assayed. In separate rats, ventricular myocytes were isolated, their size determined, and [Ca2+]i and pHi examined using fluo-3 acetoxymethyl ester and 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein tetrakis acetoxymethyl ester fluorescence, respectively.


RESULTS
Left ventricular end-diastolic pressure was increased, and the maximal rates of increase and of decrease in pressure with time in the left ventricle were decreased in SHRs compared with SDRs. Myocytes were larger and hydroxyproline was increased in the left ventricle, but not in the right ventricle of SHRs compared with SDRs. Amiloride and enalapril decreased systolic blood pressure in SHRs similarly, and improved diastolic function in these rats, enalapril more than amiloride. Both agents decreased left ventricular myocyte size to similar extents; however, whereas enalapril decreased the left ventricular hydroxyproline content, amiloride did not. Left ventricular myocytes from SHRs exhibited greater [Ca2+]i and pHi than those from SDRs; enalapril decreased [Ca2+]i more than amiloride, but amiloride decreased pHi more than enalapril.


CONCLUSIONS
In SHRs, enalapril prevents left ventricular hypertrophy, collagen deposition, diastolic dysfunction, and increases in [Ca2+]i more effectively than does amiloride. In contrast, the latter prevents the increase in pHi more effectively than enalapril, despite similar reductions in blood pressure. These findings suggest that their effects do not depend solely on blood pressure reduction.
Ji
Yong
Y
Department of Physiology and Pharmacology, Nanjing Medical University, Nanjing, China.
Huang
Yan
Y
Han
Yi
Y
Xu
Yi
Y
Ferro
Albert
A
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology*; D004656:Enalapril / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000188:drug therapy; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley
D000959:Antihypertensive Agents; D004232:Diuretics; D004656:Enalapril; D000584:Amiloride; D003094:Collagen; D002118:Calcium