Effect of a non antihypertensive dose of ramipril on the plasma and tissu renin-angiotensin system in TGR (mRen2) 27 rat

It is admitted that low dose of angiotensin converting enzyme (ACE) inhibit ors allows the regression of left ventricular hypertrophy (HVG) in experime ntal models where plasma renin activity (PRA) is high. The use of low dose of ramipril, an ACE inhibitor, make it possible to explore the place of car diac renin-angiotensin system (RAS) in the regression of HVG independently of blood pressure (BP). Twenty rats TGR (mRen2) 27, heterozygous male, 10 w eeks old were treated by daily oral gavage during 6 weeks by 10 mug/kg/jour ramipril or distilled water and compared to 10 normotensive Sprague Dawley (SD) rats. BID was measured. After the period of treatment, plasma, left k idney and the ventricles were removed. On each tissue samples and plasma, a ngiotensinogen (Aogen), the renin activity, angiotensins I (Ang II) and II (Ang II) were determined by radioimmuno assay and the activity of ACE was m easured by fluorimetry. BP does not differ between treated and untreated gr oups during 6 weeks of treatment but is significantly higher compared to SI D rats. PRA of untreated rats is high (36 +/-5 ng Ang I/mL/h). However, tre atment did not make it possible to decrease HVG. In plasma and kidney treat ment's effect on SRA is confirmed by the increase in renin activity (plasma : 63 +/-9 vs 36 +/-5 ng Ang I/mL/h; kidney: 127.1 +/- 11 vs 92 +/-7 pg Ang I/g/h) which is accompanied by an increase of Ang I rates (plasma: 297 +/- 31 vs 15 +/- 10 fmol/mL; kidney: 241 +/- 37 vs 160 +/- 12 fmol/g) and of th e reduction in Aogen. An inhibition of ACE is perceptible with low dose of ramipril in heart (left ventricle: 1.7 +/-0.1 vs 2.5 +/-0.3 nmol HisLeu/min /mg protein), but it does not appear significant modifications of the other elements of the RAS in this tissue. The Ang OO cardiac rates are probably not solely defined by cardiac ACE activity, other ways of synthesis being d escribed. The absence of regression of the HVG in TGR (mRen2) 27 rat with low dose of ramipril could be related to the absence of effect on cardiac Ang II rates . In addition, the relation between high PRA rates and the effectiveness of low dose of ACE inhibitor in the HVG are not confirmed.