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Increased soluble guanylate cyclase (sGC) activity may compensate for the high fat diet‐induced reduction in NO bioavailability of rat coronary arterioles
Author(s) -
Koller Akos,
Erdei Nora,
Feher Attila,
Edes Istvan,
Bagi Zsolt
Publication year - 2007
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.21.6.a1226-c
Subject(s) - dilator , sodium nitroprusside , medicine , nitric oxide , endocrinology , vasodilation , soluble guanylyl cyclase , bioavailability , coronary arteries , acetylcholine , obesity , vascular smooth muscle , chemistry , guanylate cyclase , pharmacology , smooth muscle , artery
We tested the idea that obesity results in a reduced endothelial nitric oxide (NO) bioavailability and thus impaired dilator responses of coronary arterioles. NO‐mediated arteriolar responses were investigated in pressurized coronary arterioles (~150 μm) isolated from high fat diet (60% of saturated fat)‐treated, obese rats. Dilations to acetylcholine (ACh) were not significantly different in obese rats compared to those of lean controls, receiving normal diet (control: 83±4%, obese: 85±3% at 1 μM). Inhibition of NO synthesis with L‐NAME reduced ACh‐induced dilations in the control group, but did not significantly affect ACh‐induced dilations in obese rats. Dilations to NO donors, sodium nitroprusside (SNP) and NONOate, however, were significantly enhanced in obese rats (control: 43±5% and 51±5%, obese: 64±7% and 61±6%, respectively at 1 μM), whereas dilations to 8‐bromo‐cGMP were not different in the 2 groups. In the presence of soluble guanylate cyclase (sGC) inhibitor, oxadiazolo‐quinoxaline SNP and NONOate‐induced dilations were reduced to the similar magnitude in both groups. The protein expressions of the sGCβ1 subunit were not different in coronary arteries of obese and control, lean rats. These findings suggest that obesity may lead to an increased activity of sGC in the smooth muscle of coronary arterioles resulting in a compensation for the reduced NO‐bioavailability. Supported by AHA NE Aff. 0555897T and Hungarian NSRF/OTKA ‐T48376 and HSC/ETT 364/2006.