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

Eva Jebelovszki, Csaba Kiraly, Nora Erdei, Attila Feher, Eniko T. Pasztor, Ibolya Rutkai, Tamas Forster, Istvan Edes, Akos Koller, Zsolt Bagi

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

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 Nω-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 ±M), 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 1-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.

Original languageEnglish (US)
Pages (from-to)H2558-H2564
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume294
Issue number6
DOIs
StatePublished - Jun 2008

Keywords

  • Dilation
  • Guanosine 3′,5′-cyclic monophosphate
  • Microcirculation
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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