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Effects of hypoxia and adrenergic stimulation induced alterations in PGI2 synthesis by diabetic coronary arteries
M Z Koltai1, P Rösen, P Hadházy
1National Institute of Cardiology, Department of Pharmacodynamics, Semmelweis Medical School, Budapest, Hungary.
Abstract:
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.
Insights
Diabetic dogs show reduced prostacyclin (PGI2) production in coronary arteries, impairing vasodilation. This diminished PGI2 synthesis, linked to adrenergic mechanisms, may explain severe ischemic heart disease in diabetes.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Biochemistry
Background:
- Diabetic arteries exhibit reduced vasodilatory capacity before histological changes.
- Prostacyclin (PGI2) plays a crucial role in vascular tone and homeostasis.
Purpose of the Study:
- To investigate the role of altered PGI2 synthesis in the impaired vasodilation of diabetic coronary arteries.
- To explore the influence of adrenergic mechanisms on PGI2 production in diabetes.
Main Methods:
- Radioimmunoassay was used to measure PGI2 synthesis in coronary artery rings from healthy and alloxan-diabetic dogs.
- Measurements were taken under baseline conditions, with phenylephrine stimulation, and during hypoxia, with and without phentolamine.
Main Results:
- Basal PGI2 synthesis was similar in healthy and diabetic arteries.
- Phenylephrine potentiated PGI2 synthesis in controls but not in diabetic arteries.
- Hypoxia increased PGI2 production in healthy arteries but decreased it in diabetic arteries (p<0.01).
- Phentolamine abolished the differences between healthy and diabetic arteries under hypoxic conditions.
Conclusions:
- Diabetic coronary arteries have diminished PGI2 production, contributing to impaired vasodilation, likely mediated by adrenergic mechanisms.
- The lack of enhanced coronary PGI2 synthesis under hypoxia in diabetes may contribute to the severity of ischemic heart disease.