Effects of hypoxia/reoxygenation on aortic vasoconstrictor responsiveness.
The purpose of the present study was to assess the effects of hypoxia/reoxygenation (H/R) on vasoconstrictor effectiveness, in vitro. Aortic rings were obtained from rats and placed on isometric force transducers in oxygenated Krebs buffer (95% O2/5% CO2, PO2 > 500 torr). Cumulative concentration/effect relationships to norepinephrine, G-protein activation by AlICl3/NaF, depolarization by KCl or BayK-8644, mobilization of intracellular calcium by caffeine, and protein kinase C activation by l-indolactam were evaluated. Hypoxia (PO2 < 5 torr) was induced by rapidly bubbling the Krebs buffer with 95% N2/5% CO2 for 15 min. Vessel rings were reoxygenated for 30 min and concentration/effect relationships reevaluated. The dissociation constant (KA) for norepinephrine was also determined. The pD2 for maximal norepinephrine responsiveness decreased from 7.7 to 7.3 following H/R. Maximal tension generation was significantly decreased following H/R. Endothelium denudation or nitric oxide synthesis inhibition did not prevent the right shift in norepinephrine concentration/effect relationship caused by H/R. The combination of superoxide dismutase and catalase prevented the dextral shift in the concentration/effect curve. The dissociation constant for norepinephrine increased from 0.16 to 0.32 microM following H/R, suggesting decreased affinity of adrenergic receptor. H/R did not alter AlCl3/NaF, KCl, BayK-8644 or l-indolactam-induced vasoconstriction. Caffeine-induced vasoconstriction was significantly impaired following H/R, suggesting that release of calcium from the sarcoplasmic reticulum is compromised. These results suggest that H/R leads to an endothelium independent, oxidant-mediated decrease in vascular norepinephrine responsiveness that may be related to defects in the mobilization of intracellular calcium from the sarcoplasmic reticulum pool.[1]References
- Effects of hypoxia/reoxygenation on aortic vasoconstrictor responsiveness. Gao, H., Korthuis, R.J., Benoit, J.N. Free Radic. Biol. Med. (1996) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
