EFFECTS OF DIFFERENT ANTIHYPERTENSIVE TREATMENTS ON MORPHOLOGIC PROGRESSION OF DIABETIC NEPHROPATHY IN UNINEPHRECTOMIZED DOGS

We previously reported the renal hemodynamic effects of different anti hypertensive regimens in uninephrectomized, alloxan-induced, diabetic (DM) beagle dogs following one year of treatment. Dogs were prospectiv ely randomized to one of five groups (N = 26): nondiabetic controls, G roup I; dogs with DM on no antihypertensive drugs, Group II; dogs on a converting enzyme inhibitor, lisinopril (L), Group III; dogs on a cal cium antagonist, TA3090 (diltiazem-like), Group IV; and dogs on a comb ination of each drug, in reduced doses, Group V. The current paper ext ends our previous studies by describing the morphologic changes that o ccurred within each group of dogs studied. More than 100 glomeruli fro m the renal cortex of each dog were evaluated for increases in mesangi al volume fraction (V-v), glomerulosclerosis (GS) and arteriolar hyali nosis. The interstitium was also evaluated for associated changes. Inc reases in V-v were attenuated in all treated groups (0.28 +/- 0.04, DM alone versus 0.16 +/- 0.05 L; 0.21 +/- 0.07, TA-3090; 0.19 +/- 0.06 m u m(2)/mu m(2), L + TA 3090; P < 0.05) compared to untreated DM. An at tenuated increase in V-v also correlated with a blunted rise in protei nuria in Groups III (r = 0.79) and V (r = 0.81) but not Group IV (r = 0.29). Development of focal GS was blunted in all treated groups; howe ver, global GS was fourfold greater in Group IV compared to untreated DM. The degree of interstitial fibrosis also correlated with the degre e of global GS. These data support the concept that both a converting enzyme inhibitor and heart rate lowering calcium antagonist attenuate morphologic progression of diabetic renal disease. When used alone, ho wever, the calcium antagonist increases development of global GS, an e ffect that appears to be independent of blood pressure control.