Effect of Trichlormethiazide and Captopril on Nitric Oxide Synthase Activity in the Kidney of Deoxycorticosterone Acetate-salt Hypertensive Rats.

Abstract

SUMMANitric oxide (NO) production is reduced in patients with essential hypertension and in some experimental models. We have investigated the effect of trichiormethiazide 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 (30mg/kg body weight (BW)) and 1% saline in drinking water after right nephrectomy. As antihypertensive therapies, CAP (captopril, 40mg/kg BW) and TCM (trichlormethiazide, 10mg/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 braintype 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. (Jpn Heart J 1996; 37; 251-259)

Glomerular Expression Of Endothelial Nitric Oxide Synthase In Deoxycorticosterone Acetate‐ Salt‐Treated Rats

“… 21,22 Hayakawa et al have shown that administration of L ‐arginine, the NO precursor, improved NO release from an isolated perfused kidney in DOCA‐salt hypertensive rats, suggesting diminished NO synthesis in the kidney. 23 Takanohashi et al 24 have also reported that eNOS expression in renal vessels was decreased by DOCA‐salt treatment, which is consistent with our results. Given these results, we suggest that long‐term volume loading induces glomerular expansion, which, in turn, damages the capillary endothelial cell and decreases eNOS expression, accelerating glomerular injury.…”

The Mineralocorticoid Receptor in Salt-Sensitive Hypertension and Renal Injury

“…Supporting this, aldosterone infusion in rodents caused hypokalemia and NCC activation, but the correction of hypokalemia by an ENaC inhibitor or potassium supplementation reversed the NCC activation. 114 Moreover, NCC inhibitors ameliorated salt-sensitive hypertension in mineralocorticoidinfused rats 115 and in mice with the kidney-specific deletion of 11b-HSD2; in both cases, NCC is activated via hypokalemia induced by activation of MR-ENaC signals in principal cells. 104 Of note, some studies offer evidence indicating a direct role of aldosterone in NCC regulation, although the modulation of NCC by aldosterone largely depends on change in plasma potassium.…”