18178725

pubmed:Citation

3

This study examines in endothelium-denuded bovine pulmonary arteries the effects of increasing heme oxygenase-1 (HO-1) activity on relaxation and soluble guanylate cyclase (sGC) activation by nitric oxide (NO). A 24-h organ culture with 0.1 mM cobalt chloride (CoCl2) or 30 microM Co-protoporphyrin IX was developed as a method of increasing HO-1 expression. These treatments increased HO-1 expression and HO activity by approximately two- to fourfold and lowered heme levels by 40-45%. Induction of HO-1 was associated with an attenuation of pulmonary arterial relaxation to the NO-donor spermine-NONOate. The presence of a HO-1 inhibitor 30 microM chromium mesoporphyrin during the 24-h organ culture (but not acute treatment with this agent) reversed the attenuation of relaxation to NO seen in arteries co-cultured with agents that increased HO-1. Relaxation to isoproterenol, which is thought to be mediated through cAMP, was not altered in arteries with increased HO-1. Inducers of HO-1 did not appear to alter basal sGC activity in arterial homogenates or expression of the beta(1)-subunit of sGC. However, the increase in activity seen in the presence of 1 microM spermine-NONOate was attenuated in homogenates obtained from arteries with increased HO-1. Since arteries with increased HO-1 had decreased levels of superoxide detected by the chemiluminescence of 5 microM lucigenin, superoxide did not appear to be mediating the attenuation of relaxation to NO. These data suggest that increasing HO-1 activity depletes heme, and this is associated with an attenuation of pulmonary artery relaxation and sGC activation responses to NO.

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http://linkedlifedata.com/resource/pubmed/journal/100901228

http://linkedlifedata.com/resource/pubmed/chemical/10,10'-dimethyl-9,9'-biacridinium, http://linkedlifedata.com/resource/pubmed/chemical/Acridines, http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Cobalt, http://linkedlifedata.com/resource/pubmed/chemical/Guanylate Cyclase, http://linkedlifedata.com/resource/pubmed/chemical/Heme, http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase-1, http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol, http://linkedlifedata.com/resource/pubmed/chemical/Mesoporphyrins, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide, http://linkedlifedata.com/resource/pubmed/chemical/Protoporphyrins, http://linkedlifedata.com/resource/pubmed/chemical/Spermine, http://linkedlifedata.com/resource/pubmed/chemical/Superoxides, http://linkedlifedata.com/resource/pubmed/chemical/chromium mesoporphyrin, http://linkedlifedata.com/resource/pubmed/chemical/cobaltiprotoporphyrin, http://linkedlifedata.com/resource/pubmed/chemical/cobaltous chloride, http://linkedlifedata.com/resource/pubmed/chemical/spermine nitric oxide complex

Mar

pubmed-author:AhmadMansoorM, pubmed-author:ChowJoseph LJL, pubmed-author:GupteSachin ASA, pubmed-author:MingoneChristopher JCJ, pubmed-author:WolinMichael SMS

294

Y

2011-9-13