ROLE OF VASCULAR ADRENERGIC-MECHANISMS IN THE HEMODYNAMIC AND PGI(2) STIMULATING EFFECTS OF ANGIOTENSIN IN DIABETIC DOGS

In aware of the well-known altered vascular responsiveness in the diab etic vasculature, this study aimed to compare the haemodynamic and PGI (2) releasing effects of angiotensin in metabolically healthy (12) and alloxan-(560 umol/kg) diabetic (12) dogs as well as to analyze the ro le of vascular adrenoceptors in this. In vivo the effect of intracoron arially administered angiotensin (63-125-250-500-1000 pmol/kg/min) on coronary blood flow, mean arterial blood pressure, myocardial contract ile force and heart rate was investigated without and with pretreatmen t of 2 umol/kg phentolamine. In vitro PGI(2) release by isolated coron ary rings was induced by 50 nmol/l angiotensin before and after pretre atment with 5 umol/l phentolamine and measured by radioimmunoassay. An giotensin enhances dose-dependently both the mean arterial blood press ure and coronary blood flow, while it provokes a considerable (p < 0.0 5) increase of PGI(2) formation by isolated coronary arterial rings. T hese alterations could be prevented by phentolamine administration bot h in vivo and in vitro, while this drug did not affect the angiotensin -induced enhancement of diabetic coronary blood flow. On the other han d the increase of blood pressure by angiotensin was found to be more ( p < 0.05) expressed in diabetes and it could be further potentiated by phentolamine. PGI(2) synthesis by isolated diabetic coronary rings co uld not be modified either by angiotensin alone or in combination with phentolamine. On the basis of above data, the lack of stimulated vasc ular PGI(2) formation mediated by alpha-adrenergic mechanisms is suppo sed to causatively contribute to the diminished sensitivity of diabeti c coronary arteries to vasodilation.