Effects of hypoxia and adrenergic stimulation induced alterations in PGI2 synthesis by diabetic coronary arteries.
Before the onset of histologically detectable alterations in diabetic arteries, a considerable decrease in vasodilatory potential is seen. While analyzing this phenomenon, the role of altered PGI2 synthesis in rings of coronary arteries from metabolically healthy and alloxan-diabetic dogs was measured by radioimmunoassay during baseline, under the influence of phenylephrine (100 mumol/L), and during hypoxia with or without the presence of the alpha adrenergic blocker phentolamine (5 mumol/L). Basal levels of PGI2 synthetized by healthy and diabetic coronaries were no different (7.9 +/- 2.1 and 6.4 +/- 1.4 pg/mg vessel). Phenylephrine potentiated PGI2 synthesis in controls (150 +/- 22%), while it proved to be ineffective in the diabetic animals (98 +/- 6%). Under hypoxic conditions, PGI2 production of healthy coronaries (152 +/- 24%) increased, while that in the diabetic ones (82 +/- 7%) decreased (p less than 0.01). In the presence of phentolamine no difference could be detected between the two groups. Given all these data, the decreased ability of the diabetic coronaries to vasodilate develops due to diminished PGI2 production, presumably controlled by adrenergic mechanisms. Furthermore, the more severe outcome of ischaemic heart disease in diabetes mellitus might be explained by the lack of an enhanced coronary PGI2 synthesis under hypoxic conditions.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000378:metabolism*; D004285:Dogs; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D011464:Epoprostenol; D010646:Phentolamine