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Nitric Oxide Synthase Knockout Modulates Ca2+‐Sensing Receptor Expression and Signaling in Mesenteric Arteries
Author(s) -
Awumey Emmanuel Modesto,
Bridges Lakeesha E,
Williams Cicely L,
Diz Debra I
Publication year - 2012
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.26.1_supplement.671.5
Subject(s) - enos , mesenteric arteries , chemistry , endocrinology , knockout mouse , medicine , nitric oxide synthase , endothelial nos , nitric oxide , vasodilation , electrical impedance myography , receptor , phenylephrine , iberiotoxin , conditional gene knockout , artery , biochemistry , gene , phenotype , blood pressure
Ca 2+ e ‐induced relaxation of mesenteric artery is dependent on the perivascular nerve (PvN) Ca 2+ ‐sensing receptor (CaSR). The CaSR stimulates a cannabinoid vasodilator pathway, with a small (~20%) nitric oxide (NO)‐dependent component. Wire myography of phenylephrine (PE)‐contracted mesenteric arteries was used to determine the source of NO contributing to CaSR‐mediated relaxation in NO synthase (NOS) gene knockout mice in combination with NOS inhibitors. . Endothelial NOS gene knockout (eNOS −/− ) up‐regulates, whereas neuronal NOS gene knockout (nNOS −/− ) down‐regulates CaSR protein expression. nNOS −/− reduced maximum Ca 2+ e ‐induced relaxation by ~ 34% with no change in EC 50 values, consistent with down‐regulation of the receptor as the non‐selective NOS inhibitor, L‐N 5 ‐(1‐Iminoethyl)‐Ornithine (10 μM) reduced Ca 2+ e ‐induced relaxation in C57BL/6 control mice by ~ 38% ( p < 0.05 ), but not eNOS −/− mice. The nNOS inhibitor, 7‐Nitroindazole had no effect on arteries from nNOS −/− mice. Both N G ‐Nitro‐L‐Arginine Methylester and N G ‐Monomethyl‐L‐Arginine reduced Ca 2+ ‐induced relaxation maxima by about 55%, 50% and 30% in C57BL/6, nNOS −/− and eNOS −/− mice, respectively. Thus eNOS down‐regulates the CaSR in mesenteric arteries and contributes to the NO‐mediated Ca 2+ ‐induced relaxation, but nNOS is not a major contributor. Support: HL064761 , HL059868 , MD000175 & HL099139