Dexamethasone worsens nitric oxide inhibition-induced hypertension and renal dysfunction

Chronic nitric oxide (NO) inhibition with N-omega-nitro-L-arginine methyl e ster (L.-NAME) has previously been reported to produce systemic hypertensio n, renal vasoconstriction, and renal damage. In this study we investigated whether a compensatory restoration of NO synthesis occurs in chronic L-NAME hypertension and whether chronic treatment with. dexamethasone (Dex) (whic h inhibits inducible NO synthase [iNOS]) can influence the course of the hy pertension. We found that in the conscious chronically L-NAME-treated ( app roximate to 10 mg/kg/24 h) hypertensive rats, acute systemic NOS inhibition elicited a further increase in blood pressure (BP), indicating partial res toration of NO production. Chronic Dex in a dose previously reported to inh ibit iNOS (5 mu g/24 h), amplified the hypertension (within 2 days), renal vasoconstriction, and reduction in glomerular filtration rate because of L- NAME. In contrast, chronic Dex alone had no effects on renal hemodynamics o r BP during the first week, although by the end of week 2 a small increase in BP ( approximate to 10 mm Hg) was evident. These results show that BP co ntinues to increase with chronic L-NAME despite partial restoration of NO p roduction. An iNOS, which might be stimulated and escaped inhibition by L-N AME, may be responsible for the compensatory restoration of NO synthesis, s erving to attenuate the development of hypertension and renal dysfunction. Am J Hypertens 2000;13:1097-1102 (C) 2000 American Journal of Hypertension, Ltd.