Relaxation of rat aorta by adenosine in diabetes with and without hypertension: role of endothelium

Effects of diabetes on the responses of aortic rings of normotensive Wistar -Kyoto (WKY) and spontaneously hypertensive (SHR) rat to adenosine analogue s were examined. Streptozotocin-induced diabetes caused an increase in bloo d glucose and plasma levels of cholesterol and triglycerides in normotensiv e (diabetic-WKY) as well as hypertensive (diabetic-SHR) rats. In diabetic-S HR group, the body weight was significantly low (50%) as compared to SHR (n on-diabetic). Diabetic-SHR group showed the largest heart weight-to-body we ight ratio indicating cardiac enlargement. The relaxation responses to aden osine analogues were obtained in endothelium-intact and -denuded aortic rin gs precontracted with phenylephrine. The IC50 values of adenosine analogues were lower in endothelium-intact aortic rings of WKY as compared to diabet ic-WKY and -SHR. Aortic rings from diabetic-SHR showed the greatest attenua tion in adenosine analogue-mediated relaxation. Removal of endothelium from the aortic rings inhibited the relaxant response of adenosine analogues an d abolished the differences among the groups. Nitric oxide (NO) synthase in hibitor L-monomethylarginine (L-NMMA) caused a significant rightward shift in the concentration-response curves in WKY and diabetic-WKY groups, only a small shift in SHR and no change in diabetic-SHR group indicating that it is primarily the inhibition of NO release which is responsible for attenuat ion of adenosine receptor responses in SHR and diabetic-WKY and there was a bsence of NO release in diabetic-SHR. Forskolin and sodium nitroprusside eq ually relaxed the aortic rings in an the groups. This suggested that there was no abnormality in the relaxant property of vascular smooth muscle due t o hypertension and/or diabetes. Therefore, it is concluded that streptozoto cin-induced diabetes in SHR aggravates the severity of vascular endothelial dysfunction which led to impairment in adenosine receptor-mediated vascula r responses. (C) 2001 Elsevier Science B.V. All rights reserved.