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Role of nitric oxide pathway in hypotensive and renal effects of furosemide during extracellular volume expansion.

Abstract：

OBJECTIVE:In previous studies we demonstrated that the administration of furosemide associated with L-arginine contributes to enhanced hypotension and induces greater water than electrolyte excretion, in both normal and expansion conditions. The aim of the present study was to elucidate the interaction between furosemide and the nitric oxide (NO) system in renal and vascular responses during extracellular volume expansion. DESIGN AND METHODS:Expanded [10% body weight (bw)] and non-expanded anaesthetized male Wistar rats were treated with furosemide (7.5 mg/kg bw). Mean arterial pressure, nitrite and nitrate excretion (NOx) were determined. NADPH-diaphorase activity, a marker of nitric oxide synthase (NOS) activity, was measured histochemically in different segments of the nephron, aorta and renal arteries. NOS activity was determined using an L-[U14C]-arginine substrate in the kidney and aorta of expanded and non-expanded rats, in basal conditions and after furosemide (10 micromol/l). RESULTS:The hypotensive effect of furosemide was enhanced when NO production was stimulated in expanded and non-expanded animals. The diuretic treatment induced a significant increase in NOx excretion, in NADPH-diaphorase activity in the thick ascending limb of Henle, renal arteries and aorta, and in NOS activity in aorta and kidney in both groups. CONCLUSIONS:Our results suggest that the hypotensive effect of furosemide may be attributed to NO-mediated vasodilation. The enhanced NOS activity, observed in the renal artery of furosemide-treated rats, could explain the increased renal plasma flow induced by furosemide. In addition, NO-pathway stimulation in the kidney could be one of the mechanisms by which furosemide exerts its diuretic and natriuretic effects, in control and in expansion conditions.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Costa MA,Loria A,Elesgaray R,Balaszczuk AM,Arranz C

doi

10.1097/01.hjh.0000125445.28861.8a

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

1561-9

issue

eissn

0263-6352

issn

1473-5598

pii

00004872-200408000-00022

journal_volume

pub_type

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Role of nitric oxide pathway in hypotensive and renal effects of furosemide during extracellular volume expansion.