期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 294, 期 3, 页码 H1244-H1250出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00846.2007
关键词
cGMP; cobalt protoporphyrin; chromium mesoporphyrin; superoxide
资金
- NHLBI NIH HHS [P01 HL043023-170002, R01 HL132574, P01 HL043023, R01 HL031069, R01 HL031069-23, R01 HL066331-07, R37 HL031069, R01 HL085352, HL-43023, HL-66331, R01 HL066331, HL-31069] Funding Source: Medline
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 mu M 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 mu M 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 cocultured 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 mu M 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 mu M 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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