EFFECTS OF EARLY AND LATE ANTIHYPERTENSIVE TREATMENT ON EXTRACELLULAR-MATRIX PROTEINS AND MONONUCLEAR-CELLS IN UNINEPHRECTOMIZED SHR

The efficacy of an early and late treatment with the angiotensin conve rting enzyme inhibitor lisinopril or the angiotensin II receptor block er ICI D8731 was investigated in uninephrectomized spontaneously hyper tensive rats (SHR). Rats that underwent uninephrectomy (UNX) at six we eks of age were randomly assigned to receive no treatment, lisinopril shortly after UNX, lisinopril starting 16 weeks after UNX, ICI D8731 s hortly after UNX, and ICI D8731 starting 16 weeks after UNX. Blood pre ssure was normalized with both treatments. After six months inulin cle arance was not significant different, while proteinuria and prevalence of interstitial fibrosis were significantly reduced in all treatment groups. Immunohistochemical studies revealed an interstitial, periglom erular and perivascular increase of extracellular matrix proteins in a ll rats, but a markedly reduced expression of collagen I, IV and fibro nectin after early and late treatment compared to untreated controls. We found a significant reduction of infiltrating macrophages and T-lym phocytes in all treated animals compared to untreated controls after 2 , 4 and 6 months. Especially early treatment was associated with lower numbers of infiltrating cells. Both treatments reduced proliferation of tubular and interstitial cells. There were no striking differences with regard to nephroprotection between the ACE inhibitor and angioten sin II receptor blocker. These findings show that both treatments have beneficial effects on kidney structure and function. They suggest tha t both ACE inhibition and angiotensin II blockade decrease renal cell proliferation and suppress the infiltration of mononuclear cells that may trigger expression of extracellular matrix proteins and progressiv e nephrosclerosis.