Relationship between vascular adrenergic receptors and prostaglandin biosyntheses in canine diabetic coronary arteries

Before the onset of histologically detectable alterations of diabetic arteries, a considerable decrease of vasodilation ability develops. The role of an altered prostaglandin biosynthesis in this phenomenon was investigated in connection to the altered vascular adrenergic mechanisms. The effect of phenylephrine on prostacyclin production of isolated coronary arterial rings (100 mumol/l) as well as on conductivity of the coronary arterial bed (7.5-15-30-60 pmol. kg-1.min-1) were compared in 12 metabolically healthy and 12 alloxan-diabetic (560 mumol/kg) dogs. Furthermore, the effect of phentolamine (5 mumol/l) on the prostacyclin and thromboxane productions of the isolated vessels (coronary, femoral and basilar arteries) was investigated by radioimmunoassay. Although the basal prostacyclin amounts synthesized by healthy and diabetic coronary vessels were not different (5.1 +/- 1.6 and 4.9 +/- 1.4 pg/mg vessel/30 min), similarly to femoral and basilar arteries, the diabetic arterial rings produced significantly (p less than 0.05) more thromboxane than the control rings. The alpha-adrenergic blockade by phentolamine did not influence the prostacyclin production in the healthy arteries, but considerably (p less than 0.05) increased it in the diabetic coronary arteries. Phentolamine normalised the thromboxane synthesis in the diabetic group (p less than 0.01) and enhanced (p less than 0.05) it in the metabolically healthy group. Phenylephrine was ineffective (98 +/- 6%) on the prostacyclin production in vitro versus the stimulated (150 +/- 22%) prostacyclin synthesis detected in the metabolically healthy group; and in vivo induced a more significant (p less than 0.05) decrease in the coronary conductivity in diabetic than in control groups.