Significant Suppressive Effect of Low-Dose Temocapril, an ACE Inhibitor with Biliary Excretion, on FGS Lesions in Hypertensive Rats

Abstract

To investigate how the interruption of the renin-angiotensin system (RAS) and reduction of blood pressure (BP) affect the lesions of chronic focal and segmental glomerulosclerosis (FGS), we studied the effects of high and low doses of angiotensin-converting enzyme inhibitors (temocapril – TEM) a newly developed ACE inhibitor with biliary tract excretion, on the hypertensive model of FGS. A high dose of TEM significantly lowered BP and suppressed both intense proteinuria and glomerular extracapillary lesions including macrophage infiltration. On the other hand, although a low dose of TEM did not significantly lower BP throughout the experimental period, it prevented renal lesions almost in the same manner as high-dose TEM with suppression of c-myc gene expression in glomeruli. These findings suggest that in PAN-induced chronic FGS, the systemic BP elevation could not be the major factor for the progression of renal damage which TEM could prevent without significant lowering of BP.

Renoprotection persists after cessation of treatment with very low doses of perindopril in Lyon hypertensive rats

“…Originally, the renoprotective effects of antihypertensive agents were attributed solely to their BP-lowering potential. However, blockers of the renin-angiotensin system (RAS), such as angiotensin-converting enzyme (ACE) inhibitors, seem able to provide renoprotection even without modifying BP [3][4][5][6][7][8][9][10][11] . However this concept of BP-independent renoprotection by RAS blockers was recently challenged on the basis that episodic measurements of BP did not allow an accurate assessment of the pressure load to the kidneys.…”