Contrasting effects of streptozotocin-induced diabetes on the in vitro relaxant properties of adenosine in rat pancreatic vascular bed and thoracic aorta.
In the present work, we have studied adenosine-induced vasodilation in streptozotocin-induced diabetic rats and compared it to that observed in normal age-matched or weight-matched animals. Experiments were performed on a vascular bed, the isolated perfused pancreas, and a large vessel, the thoracic aorta, provided from the same animal. Vasodilator activity was assessed, for isolated pancreas, as the increase in flow induced by the infusion of 2 microM adenosine for 30 min, or for noradrenaline-contracted aortae, as the relaxant response to adenosine (1 microM-1 mM). In both preparations the results obtained with selective adenosine receptors ligands (CPA, CGS 21680 and NECA) agreed with the presence of adenosine receptor of A2a subtype. In normal animals, adenosine vasodilator activity on both preparations diminished with advancing age in the rat, while diabetes was associated with a decreased or increased responsiveness to adenosine in pancreatic vascular bed or aorta, respectively. Further, the involvement of nitric oxide (NO), in relaxant responses, was evaluated by the use of the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). In all groups of animals, the flow rate of isolated pancreas dropped in the presence of 200 microM L-NAME, but was restored by adenosine to the level observed without L-NAME. L-NAME (10 microM) significantly reduced the dilator response to adenosine in aortic rings from diabetic animals, but not in those from normal rats. These results showed that adenosine vasorelaxant activity is significantly but differentially altered by diabetes according to the origin of the vascular preparation, and suggest that NO is involved in the vasorelaxant activity of adenosine in large vessels of diabetic animals. The potential pathophysiological role of adenosine in the vascular complications of diabetes remains to be determined.
Laurent
F
F
Laboratoire de Pharmacologie (UPRES EA 2035), Faculté de Pharmacologie, Montpellier, France.
Hillaire-Buys
D
D
Chapal
J
J
Dietz
S
S
Portet
K
K
Cros
G
G
Petit
P
P
Michel
A
A
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000503:physiopathology; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester