Abstract
The effects of glucose on endothelium-dependent responses and vasoactive prostanoid production were determined by incubating isolated rabbit aortae in control (5.5 or 11 mM) or elevated (44 mM) glucose for 6 h to mimic euglycemic and hyperglycemic conditions. Rings of aortae incubated in elevated glucose, contracted submaximally by phenylephrine, showed significantly decreased endothelium-dependent relaxations induced by acetylcholine compared with the aortae incubated in control glucose. Treatment with indomethacin, a cyclooxygenase inhibitor, or SQ29548, a prostaglandin H2/thromboxane A2 receptor antagonist, restored acetylcholine relaxations of rings in elevated glucose to normal, while these agents had no effect on the relaxation of rings incubated in control glucose. Aortae incubated with mannose (44 mM) as a hyperosmotic control relaxed to acetylcholine normally. The relaxations in response to A23187 and sodium nitroprusside were not different between rings exposed to control and elevated glucose. Radioimmunoassay measurements showed a significant increase in acetylcholine-stimulated release of thromboxane A2 and prostaglandin F2 alpha in aortae with, but not without endothelium incubated with elevated, but not with control glucose. Thus a possible mechanism for endothelium dysfunction in diabetes mellitus is the hyperglycemia-induced increased generation of endothelium-derived vasoconstrictor prostanoids.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Beetens J. R., Van Hove C., Rampart M., Herman A. G. Acetylcholine stimulates the release of prostacyclin by rabbit aorta endothelium. J Pharm Pharmacol. 1983 Apr;35(4):251–252. doi: 10.1111/j.2042-7158.1983.tb02924.x. [DOI] [PubMed] [Google Scholar]
- Boeynaems J. M., Galand N. Cholinergic stimulation of vascular prostacyclin synthesis. Prostaglandins. 1983 Oct;26(4):531–544. doi: 10.1016/0090-6980(83)90191-0. [DOI] [PubMed] [Google Scholar]
- Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
- Gerrard J. M., Stuart M. J., Rao G. H., Steffes M. W., Mauer S. M., Brown D. M., White J. G. Alteration in the balance of prostaglandin and thromboxane synthesis in diabetic rats. J Lab Clin Med. 1980 Jun;95(6):950–958. [PubMed] [Google Scholar]
- Jakubowski J. A., Stampfer M. J., Vaillancourt R., Deykin D. Cumulative antiplatelet effect of low-dose enteric coated aspirin. Br J Haematol. 1985 Aug;60(4):635–642. doi: 10.1111/j.1365-2141.1985.tb07467.x. [DOI] [PubMed] [Google Scholar]
- Meraji S., Jayakody L., Senaratne M. P., Thomson A. B., Kappagoda T. Endothelium-dependent relaxation in aorta of BB rat. Diabetes. 1987 Aug;36(8):978–981. doi: 10.2337/diab.36.8.978. [DOI] [PubMed] [Google Scholar]
- Ogletree M. L., Harris D. N., Greenberg R., Haslanger M. F., Nakane M. Pharmacological actions of SQ 29,548, a novel selective thromboxane antagonist. J Pharmacol Exp Ther. 1985 Aug;234(2):435–441. [PubMed] [Google Scholar]
- Oyama Y., Kawasaki H., Hattori Y., Kanno M. Attenuation of endothelium-dependent relaxation in aorta from diabetic rats. Eur J Pharmacol. 1986 Dec 2;132(1):75–78. doi: 10.1016/0014-2999(86)90013-0. [DOI] [PubMed] [Google Scholar]
- Quilley J., McGiff J. C. Arachidonic acid metabolism and urinary excretion of prostaglandins and thromboxane in rats with experimental diabetes mellitus. J Pharmacol Exp Ther. 1985 Jul;234(1):211–216. [PubMed] [Google Scholar]
- Rapoport R. M., Murad F. Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cGMP. Circ Res. 1983 Mar;52(3):352–357. doi: 10.1161/01.res.52.3.352. [DOI] [PubMed] [Google Scholar]
- Ruderman N. B., Haudenschild C. Diabetes as an atherogenic factor. Prog Cardiovasc Dis. 1984 Mar-Apr;26(5):373–412. doi: 10.1016/0033-0620(84)90011-2. [DOI] [PubMed] [Google Scholar]
- Saenz de Tejada I., Goldstein I., Azadzoi K., Krane R. J., Cohen R. A. Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. N Engl J Med. 1989 Apr 20;320(16):1025–1030. doi: 10.1056/NEJM198904203201601. [DOI] [PubMed] [Google Scholar]
- Subbiah M. T., Dietemeyer D. Altered synthesis of prostaglandins in platelet and aorta from spontaneously diabetic Wistar rats. Biochem Med. 1980 Apr;23(2):231–235. doi: 10.1016/0006-2944(80)90076-9. [DOI] [PubMed] [Google Scholar]
- Truog W. E., Sorensen G. K., Standaert T. A., Redding G. J. Effects of the thromboxane synthetase inhibitor, dazmegrel (UK 38,485), on pulmonary gas exchange and hemodynamics in neonatal sepsis. Pediatr Res. 1986 May;20(5):481–486. doi: 10.1203/00006450-198605000-00020. [DOI] [PubMed] [Google Scholar]
- Turek J. V., Houtsmuller U. M., Lussenburg R. N., den Ottolander G. J. Effect of low cholesterol, linoleic acid enriched diet on thrombotic tendency and plasma lipoproteins in patients with angina pectoris. Artery. 1980;8(2):134–139. [PubMed] [Google Scholar]
- Wakabayashi I., Hatake K., Kimura N., Kakishita E., Nagai K. Modulation of vascular tonus by the endothelium in experimental diabetes. Life Sci. 1987 Feb 16;40(7):643–648. doi: 10.1016/0024-3205(87)90265-7. [DOI] [PubMed] [Google Scholar]