Dexamethasone worsens nitric oxide inhibition-induced hypertension and renal dysfunction.
Chronic nitric oxide (NO) inhibition with Nomega-nitro-L-arginine methyl ester (L-NAME) has previously been reported to produce systemic hypertension, 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) (which inhibits inducible NO synthase [iNOS]) can influence the course of the hypertension. We found that in the conscious chronically L-NAME-treated (approximately =10 mg/kg/24 h) hypertensive rats, acute systemic NOS inhibition elicited a further increase in blood pressure (BP), indicating partial restoration of NO production. Chronic Dex in a dose previously reported to inhibit iNOS (5 microg/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 or BP during the first week, although by the end of week 2 a small increase in BP (approximately =10 mm Hg) was evident. These results show that BP continues to increase with chronic L-NAME despite partial restoration of NO production. An iNOS, which might be stimulated and escaped inhibition by L-NAME, may be responsible for the compensatory restoration of NO synthesis, serving to attenuate the development of hypertension and renal dysfunction.
Qiu
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Department of Physiology, Robert C. Byrd Health Sciences Center of West Virginia University, Morgantown 26506-9229, USA.
Baylis
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D009569:Nitric Oxide; D003907:Dexamethasone; D019331:NG-Nitroarginine Methyl Ester