Abstract：
:Soluble guanylyl cyclase (sGC) is a key enzyme of the NO-cGMP pathway which is believed to mediate vasoprotective actions. In cardiovascular diseases such as hypercholesterolemia and atherosclerosis, these important functions of the vascular endothelium are strongly impaired. One of the major reasons for this so-called endothelial dysfunction is the increased vascular generation of reactive oxygen species such as superoxide and peroxynitrite. We aimed to investigate whether superoxide and peroxynitrite impacts on the expression and function of sGC and if such a mechanism occurs in a hypercholestemia-induced atherosclerosis. Our experiments with isolated rat aortic rings showed that extracellular superoxide has no effect on expression and function of sGC, while subjection of these rings to continuously generated extracellular peroxynitrite reduced sGC activity. Furthermore, intracellular superoxide as generated by LY85385 almost completely inhibited sGC-activity and increased its expression. In the cholesterol-fed White New Zealand rabbit, we found a 3.5-fold upregulation of sGC, while basal and NO-stimulated sGC-activities were only slightly enhanced and the vasodilator potency of SNAP was decreased by 10-fold. A great portion of the overexpressed dysfunctional sGC is located in intimal lesions. Finally, platelet sGC-activity and the anti-aggregatory effect of SNAP were not changed. These data suggest that endothelial dysfunction in hypercholesterolemia is associated with an oxidative stress-dependent and reversible overexpression of a dysfunctional vascular sGC, while inhibition of platelet sGC-activity is most likely not involved in hypercholesterolemia-induced platelet hyperreactivity.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Francois M,Kojda Gdoi
10.1016/j.neuint.2004.03.026subject
Has Abstractpub_date
2004-11-01 00:00:00pages
955-61issue
6eissn
0197-0186issn
1872-9754pii
S0197018604000749journal_volume
45pub_type
杂志文章,评审abstract：:There is experimental evidence from radioligand binding experiments for the existence of strong antagonistic interactions between different subtypes of adenosine and dopamine receptors in the striatum, mainly between adenosine A1 and dopamine D1 and between adenosine A2A and dopamine D2 receptors. These interactions s...
journal_title：Neurochemistry international
pub_type： 杂志文章
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journal_title：Neurochemistry international
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journal_title：Neurochemistry international
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journal_title：Neurochemistry international
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journal_title：Neurochemistry international
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journal_title：Neurochemistry international
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journal_title：Neurochemistry international
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journal_title：Neurochemistry international
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journal_title：Neurochemistry international
pub_type： 杂志文章
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journal_title：Neurochemistry international
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journal_title：Neurochemistry international
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