Effects of tight blood pressure control on glomerular hypertrophy in a model of genetic hypertension and experimental diabetes mellitus.
The aim of this study was to evaluate the effect of prevention of hypertension on glomerular hypertrophy, renal cell replication and accumulation of glomerular fibronectin in a model of genetic hypertension and experimental diabetes. Four-week-old streptozotocin induced spontaneously hypertensive rats (SHR) were randomized for no treatment, or for treatment with captopril, losartan or triple therapy (hydrochlorothiazide, reserpine and hydralazine) for 20 days. Increase in systolic blood pressure was equally prevented by captopril (118+/-15 mmHg), losartan (111+/-9) and triple therapy (112+/-14, p<0.0001). Glomerular size was higher (p<0.005) in diabetic SHR (27,300+/-2130 microm(2)) compared with non-diabetic SHR (23,800+/-307). The antihypertensive therapy with captopril (23,900+/-175), losartan (23,800+/-120), and triple therapy (23,400+/-210) prevented the glomerular enlargement in diabetic SHR. Glomerular expression of fibronectin was increased in diabetic SHR (7.61+/-1.22 densitometric unit) as compared to the controls (2.27+/-2.15, p<0.0001), and was decreased (p<0.0001 vs diabetic SHR) with captopril (2.49+/-1.42), losartan (1.57+/-1.1) and triple therapy (2.04+/-1.42). The number of replicating glomerular cell significantly decreased in diabetic SHR and it was restored by all three antihypertensive regimes. The glomerular expression of p27(Kip1) was increased in diabetic SHR but it was not modified by antihypertensive treatment. Strict blood pressure control, in diabetic SHR independently of the class of antihypertensive agent, restores glomerular hypertrophy and renal cellular replication, and prevents the increment in glomerular fibronectin.
Amazonas
Roberto Bleuel
RB
Laboratory of Renal Pathophysiology, Nephrology Unit, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Lopes de Faria
José B
JB
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002216:Captopril / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents; D002216:Captopril