Effect of trichlormethiazide and captopril on nitric oxide synthase activity in the kidney of deoxycorticosterone acetate-salt hypertensive rats.
Nitric oxide (NO) production is reduced in patients with essential hypertension and in some experimental models. We have investigated the effect of trichlormethiazide and captopril on NO synthase (NOS) activity and glomerular damage in the kidney of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. DOCA-salt rats were induced with weekly injections of DOCA (30 mg/kg body weight (BW) and 1% saline in drinking water after right nephrectomy. As antihypertensive therapies, CAP (captopril, 40 mg/kg BW) and TCM (trichlormethiazide, 10 mg/kg BW) were given after induction of DOCA-salt hypertension. The increased blood pressure was significantly lowered by TCM, but not by CAP after 5 weeks. Nitrite production in kidney slices was suppressed in DOCA-salt rats, and immunoreactivity for both brain-type NOS (B-NOS) in macula densa and endothelial-type NOS (EC-NOS) in renal vessels was decreased. TCM significantly increased the nitrite production in the kidney slices and B-NOS immunoreactivity, whereas these changes were less in CAP. Glomerulosclerosis score was significantly higher in DOCA-salt rats, and TCM ameliorated renal damage more effectively than CAP. These results indicate that the reduced nitrite production in the kidney of DOCA-salt hypertensive rats was increased more effectively by trichlormethiazide than by captopril, via increased immunoreactivity for B-NOS in the macula densa, and prevented renal damage.
Takanohashi
A
A
Department of Internal Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
Tojo
A
A
Kobayashi
N
N
Yagi
S
S
Matsuoka
H
H
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use*; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D007668:Kidney / Q000201:enzymology*; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride; D014237:Trichlormethiazide / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D009573:Nitrites; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D002216:Captopril; D019001:Nitric Oxide Synthase; D014237:Trichlormethiazide