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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/H2558    most recent 01198.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Jebelovszki, E. Articles by Bagi, Z. Search for Related Content PubMed PubMed Citation Articles by Jebelovszki, E. Articles by Bagi, Z.

High-fat diet-induced obesity leads to increased NO sensitivity of rat coronary arterioles: role of soluble guanylate cyclase activation

¹Second Department of Medicine and Center of Cardiology, University of Szeged, Szeged; ²Institute of Cardiology, University of Debrecen, Debrecen; ³Department of Pathophysiology and Gerontology, University of Pecs, Pecs, Hungary; and ⁴Department of Physiology, New York Medical College, Valhalla, New York

Submitted 15 October 2007 ; accepted in final form 7 April 2008

The impact of obesity on nitric oxide (NO)-mediated coronary microvascular responses is poorly understood. Thus NO-mediated vasomotor responses were investigated in pressurized coronary arterioles (100 µm) isolated from lean (on normal diet) and obese (fed with 60% of saturated fat) rats. We found that dilations to acetylcholine (ACh) were not significantly different in obese and lean rats (lean, 83 ± 4%; and obese, 85 ± 3% at 1 µM), yet the inhibition of NO synthesis with N-nitro-L-arginine methyl ester reduced ACh-induced dilations only in vessels of lean controls. The presence of the soluble guanylate cyclase (sGC) inhibitor oxadiazolo-quinoxaline (ODQ) elicited a similar reduction in ACh-induced dilations in the two groups of vessels (lean, 60 ± 11%; and obese, 57 ± 3%). Dilations to NO donors, sodium nitroprusside (SNP), and diethylenetriamine (DETA)-NONOate were enhanced in coronary arterioles of obese compared with lean control rats (lean, 63 ± 6% and 51 ± 5%; and obese, 78 ± 5% and 70 ± 5%, respectively, at 1 µM), whereas dilations to 8-bromo-cGMP were not different in the two groups. In the presence of ODQ, both SNP and DETA-NONOate-induced dilations were reduced to a similar level in lean and obese rats. Moreover, SNP-stimulated cGMP immunoreactivity in coronary arterioles and also cGMP levels in carotid arteries were enhanced in obese rats, whereas the protein expression of endothelial NOS and the sGC β₁-subunit were not different in the two groups. Collectively, these findings suggest that in coronary arterioles of obese rats, the increased activity of sGC leads to an enhanced sensitivity to NO, which may contribute to the maintenance of NO-mediated dilations and coronary perfusion in obesity.

microcirculation; nitric oxide; guanosine 3',5'-cyclic monophosphate; dilation