Significant suppressive effect of low-dose temocapril, an ACE inhibitor with biliary excretion, on FGS lesions in hypertensive rats.
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.
Suyama
K
K
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Muso
E
E
Yashiro
M
M
Sasayama
S
S
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D015152:Blotting, Northern; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006973:Hypertension / Q000150:complications* / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D009929:Organ Size / Q000502:physiology; D011479:Protamines; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D011692:Puromycin Aminonucleoside; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D013841:Thiazepines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D000964:Antimetabolites, Antineoplastic; D011479:Protamines; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013841:Thiazepines; D016212:Transforming Growth Factor beta; D011692:Puromycin Aminonucleoside; C055603:temocapril hydrochloride