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iNOS inhibition in renal hemodynamics and blood pressure
Author(s) -
Branson Linda F.,
Kotyk John J.,
Baldwin Steven J.,
Connor Jane R.,
Payne Maria A.,
Manning Pamela T.,
Pomposiello Silvia I.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1138-b
Subject(s) - chemistry , nitric oxide synthase , nitric oxide , in vivo , vasodilation , enos , kidney , metabolite , hemodynamics , renal blood flow , pharmacology , endocrinology , mean arterial pressure , nitroarginine , medicine , blood pressure , renal function , biochemistry , biology , heart rate , microbiology and biotechnology , organic chemistry
Nitric oxide (NO), a mediator of vascular homeostasis, is produced by nitric oxide synthase (NOS) and although all three isoforms are found in the kidney, their relative contribution to the control of renal hemodynamics is not clear. We studied the effects of a nonselective NOS inhibitor, N‐nitro‐L‐arginine‐methyl ester (L‐NAME) and a selective iNOS inhibitor, L‐N 6 ‐(1‐iminoethyl)lysine 5‐tetrazole amide (SC‐51) and/or its active metabolite L‐N 6 ‐(1‐iminoethyl)lysine (L‐NIL), in vitro on endothelium‐dependent relaxation (EDR) and in vivo on mean arterial pressure (MAP) and renal blood flow (RBF) in normal rats. The selectivity of L‐NAME and L‐NIL were compared in rat aortic rings and L‐NAME inhibited the EDR elicited by acetylcholine (ACh) at 10, 30 and 60 μM. In contrast, 10 μM of L‐NIL, which inhibits iNOS activity, did not inhibit EDR. At 30 and 100 μM EDR was inhibited in a concentration‐dependent manner, demonstrating inhibition of eNOS. In vivo, cortical RBF (cRBF) was measured in anesthetized rats by magnetic resonance imaging (MRI), after infusion of inhibitor, followed by direct measurement of MAP. L‐NAME at 3 but not 0.1 mg/kg, decreased cRBF and increased MAP. SC‐51, at 10 and 30 mg/kg, produced no or slight elevations in MAP, while 100 mg/kg, elevated MAP to a similar extent as 3 mg/kg L‐NAME, consistent with inhibition of eNOS. However, SC‐51 did not lower cRBF at any dose, even those that increased MAP. These data show that the effects on RBF seen with SC‐51 and L‐NAME did not correlate with the increase in systemic MAP, suggesting different functional sensitivities to the level of eNOS inhibition in the kidney and vascular.