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Modulation Of Cyclosporine‐Induced Hypertension By Central Endothelial And Neuronal Nitric Oxide Synthases
Author(s) -
ElMas Mahmoud M,
Omar Amal G,
Helmy Mai M,
Mohy ElDin Mahmoud M
Publication year - 2010
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.24.1_supplement.959.10
Subject(s) - nitric oxide , pharmacology , chemistry , vasodilation , nitric oxide synthase , sympatholytic , endocrinology , moxonidine , blood pressure , medicine , receptor , agonist
We recently reported an intermediary role for central sympathoexcitatory neurons in the hypertensive action of acute cyclosporine (CSA) in conscious rats. Here, we report on the role of central nitrergic pathways, which negatively correlate with sympathetic outflow, in CSA hypertension. CSA (20 mg/kg i.v.) produced an abrupt increase in blood pressure that was maintained for at least 45 min. Intracisternal (i.c.) administration of N ω ‐nitro‐L‐arginine methyl ester (L‐NAME, nonselective NOS inhibitor), or 1H‐[1,2,4] oxadiazolo[4,3‐a] quinoxalin‐1‐one (guanylate cyclase inhibitor), or L‐arginine (NOS substrate) abolished the hypertensive action of CSA, suggesting a role for inhibition of NO/GC signaling in CSA response. CSA hypertension was also reduced after selective inhibition of endothelial or neuronal NOS by i.c. N 5 ‐(1‐iminoethyl)‐L‐ornithine and N ω ‐propyl‐L‐arginine, respectively, implicating both constitutive NOS isoforms in the hypertensive response. Consistent with the sympathoinhibitory role of central NOS, i.c. L‐NAME attenuated the hypotensive action of the central sympatholytic drug moxonidine. It is concluded that the inhibition of constitutive NOS isoforms and downstream GC/cGMP underlies the acute hypertensive, and perhaps the causally related sympathoexcitatory, action of CSA.