Selective inhibition of endothelium-dependent vasodilator capacity by Escherichia coli endotoxemia
| العنوان: | Selective inhibition of endothelium-dependent vasodilator capacity by Escherichia coli endotoxemia |
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| المؤلفون: | J L Parker, H R Adams |
| المصدر: | Circulation Research. 72:539-551 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 1993. |
| سنة النشر: | 1993 |
| مصطلحات موضوعية: | Lipopolysaccharides, Male, Agonist, medicine.medical_specialty, Physiology, Thromboxane, medicine.drug_class, Guinea Pigs, Substance P, Arginine, Nitric oxide, chemistry.chemical_compound, Internal medicine, Escherichia coli, medicine, Animals, Dazoxiben, Calcimycin, biology, Endothelium-derived relaxing factor, Shock, Septic, Acetylcholine, Adenosine Diphosphate, Vasodilation, Nitric oxide synthase, NG-Nitroarginine Methyl Ester, Endocrinology, chemistry, biology.protein, Endothelium, Vascular, Thromboxane-A synthase, Cyclooxygenase, Cardiology and Cardiovascular Medicine |
| الوصف: | Increased release of endothelium-derived relaxing factor/nitric oxide has been proposed as the final common pathway for vasodilator responses to gram-negative lipopolysaccharide (endotoxin). To test this hypothesis, we examined endothelium-dependent and endothelium-independent vasodilator agents in vascular smooth muscle isolated from guinea pigs 16 hours after injection of saline (control group) or induction of Escherichia coli endotoxemia; aortic rings (approximately 1 mm in diameter) were studied with standard isometric tension techniques. Endotoxemia resulted in a significant loss of vasodilator responses to the endothelium-dependent receptor agonists acetylcholine (10(-10)-10(-5) M) and ADP (10(-8)-10(-5) M). In contrast, endotoxemia did not affect vasodilator responses to either the endothelium-dependent receptor agonist substance P (10(-11)-10(-7) M), the endothelium-dependent and receptor-independent agonist A23187 (10(-9)-10(-6) M), or the endothelium-independent agonist nitroprusside (10(-10)-10(-4) M). The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) inhibited the vasodilator response to acetylcholine more in vessels from lipopolysaccharide-injected than control guinea pigs. Unexpectedly, L-NAME converted the endothelium-dependent vasodilator action of ADP to an endothelium-dependent vasoconstrictor response that was blocked individually by the cyclooxygenase inhibitor indomethacin, the thromboxane synthase inhibitor dazoxiben, and the thromboxane A2 receptor antagonist SQ29548. We conclude that in vivo endotoxemia inhibits the constitutive isoform of nitric oxide synthase in endothelial cells by selectively disrupting receptor-coupled activation mechanisms shared by acetylcholine and ADP. Furthermore, since L-NAME unmasks a thromboxane A2-mediated vasoconstrictor action of the endogenous purinoceptor agonist ADP, drugs that inhibit nitric oxide synthase could exacerbate sepsis-induced vasoconstriction and ischemia by synergizing with lipopolysaccharide-induced inhibition of endothelial nitric oxide synthase. |
| تدمد: | 1524-4571 0009-7330 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bcc5c487c737bb12cf08ca2e0fb90f58 https://doi.org/10.1161/01.res.72.3.539 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....bcc5c487c737bb12cf08ca2e0fb90f58 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244571 00097330 |
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