Protein remodelling of the heart in NO-deficient hypertension: the effect of captopril.
Long-term administration of NG-nitro-L-arginine methyl ester (L-NAME) induces development of NO-deficient hypertension. The aim of the present study was to determine whether treatment with the angiotensin-converting enzyme (ACE) inhibitor captopril can prevent hypertension, left ventricular (LV) hypertrophy, changes in nucleic acid concentration, protein synthesis and protein profile of the left ventricle. Four groups of rats were investigated: control, L-NAME 40 mg/kg/day, captopril 100 mg/kg/day, L-NAME 40 mg/kg/day along with captopril 100 mg/kg/day. NO-synthase activity in the left ventricle was found to be decreased by 69% in the L-NAME group. Captopril did not influence this inhibition of NO-synthase activity. However, it completely prevented hypertension and left ventricular hypertrophy development. The increase in left ventricular RNA and DNA concentration and -14C-leucine incorporation observed in the L-NAME group was completely prevented by simultaneous captopril treatment. The protein profile of the left ventricle in the L-NAME group was characterized by higher concentration of metabolic proteins (MP), soluble collagenous proteins (SCP) and of hydroxyproline in insoluble collagenous proteins (ICP). The concentration of hydroxyproline in ICP was significantly decreased by simultaneous captopril treatment. We conclude that captopril prevented the development of hypertension, left ventricular hypertrophy, increase in nucleic acid concentration and diminished collagen concentration by mechanisms different from affecting NO-synthase activity.
Pechánová
O
O
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Slovak Republic.
Bernátová
I
I
Pelouch
V
V
Simko
F
F
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012313:RNA / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D009124:Muscle Proteins; D009569:Nitric Oxide; D012313:RNA; D002216:Captopril; D019001:Nitric Oxide Synthase; D007930:Leucine