EFFECT OF TRICHLORMETHIAZIDE AND CAPTOPRIL ON NITRIC-OXIDE SYNTHASE ACTIVITY IN THE KIDNEY OF DEOXYCORTICOSTERONE ACETATE-SALT HYPERTENSIVERATS

Nitric oxide (NO) production is reduced in patients with essential hyp ertension and in some experimental models. We have investigated the ef fect of trichlormethiazide and captopril on NO synthase (NOS) activity and glomerular damage in the kidney of deoxycorticosterone acetate (D OCA)-salt hypertensive rats. DOCA-salt rats were induced with weekly i njections of DOCA (30 mg/kg body weight (BW)) and 1% saline in drinkin g water after right nephrectomy As antihypertensive therapies, CAP (ca ptopril, 40 mg/kg BW) and TCM (trichlormethiazide, 10 mg/kg BW) were g iven after induction of DOCA-salt hypertension The increased blood pre ssure was significantly lowered by TCM, but not by CAP after 5 weeks, Nitrite production in kidney slices was suppressed;, DOCA-salt rats, a nd immunoreactivity for both brain-type NOS (B-NOS) in macula densa an d endothelial-type NOS (EC-NOS) in renal vessels was decreased. TCM si gnificantly increased the nitrite production in the kidney slices and B-NOS immunoreactivity, whereas these changes were less in CAP, Glomer ulosclerosis score was significantly higher in DOCA-salt rats, and TCM ameliorated renal damage more effectively than CAP. These results ind icate that the reduced nitrite production in the kidney of DOCA-salt h ypertensive rats was increased more effectively by trichlormethiazide than by captopril, via increased immunoreactivity for B-NOS in the mac ula densa, and prevented renal damage.