temocapril-hydrochloride and Glomerulosclerosis--Focal-Segmental

A high-fructose diet (HFD) has been shown to elevate blood pressure (BP) and to decrease insulin sensitivity in rats. Although running exercise can attenuate these phenomena, its effect on target organ protection is not clear. We investigated whether exercise training has renal protective effects in this model. Nine-week-old spontaneously hypertensive rats were allocated to groups that received HFD or a control diet (control group) for 15 weeks. At the age of 10 weeks, fructose-fed rats were allocated to groups that were given vehicle (FRU group), temocapril, an angiotensin converting enzyme inhibitor (TEM group), exercise training (EX group; treadmill running), or temocapril plus exercise training (TEM+EX group). BP was higher in the FRU group than in the control group. Exercise training tended to decrease BP and temocapril treatment decreased BP significantly. Proteinuria was similar in the five groups. Plasma leptin concentration and epididymal fat weight were lower in the EX and TEM+EX groups than in the FRU group. In the soleus muscle of the FRU group, the composite ratio of type I fiber was decreased and that of type IIa fiber was increased compared with those in the control group. Both temocapril and exercise training restored these ratios. The glomerular sclerosis index (GSI) was higher in the FRU group than in the control group. GSI was decreased equally in the TEM, EX, and TEM+EX groups and was positively correlated with plasma leptin concentration. The results suggest that exercise training ameliorates glomerular sclerosis through mechanisms other than a reduction in BP.

Topics: Aging; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Body Composition; Body Weight; Diet; Fructose; Glomerulosclerosis, Focal Segmental; Hypertension; Kidney Glomerulus; Leptin; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Organ Size; Physical Conditioning, Animal; Proteinuria; Rats; Rats, Inbred SHR; Thiazepines

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.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Antimetabolites, Antineoplastic; Bile; Blood Pressure; Blotting, Northern; Glomerulosclerosis, Focal Segmental; Hypertension; Immunohistochemistry; Male; Organ Size; Protamines; Proto-Oncogene Proteins c-myc; Puromycin Aminonucleoside; Rats; Rats, Inbred SHR; RNA, Messenger; Thiazepines; Transforming Growth Factor beta