[Decrease of vascular response to iloprost in diabetic rats].
The functional dilatory response in the streptozotocin-induced diabetic rat was investigated using thoracic aortas and coronary microcirculation. The aortas were cut in 4 mm intact or denuded rings and mounted into 20-ml organ baths. Coronary microcirculation was evaluated with isolated hearts perfused under constant flow conditions. Firstly, vasodilation to iloprost (Ilo) was examined. Dose-response curves to Ilo (10 pM-10 microM) on phenylephrine (PE, 30 nM for endothelium-denuded, and 0.3 microM for intact) preconstricted rings of diabetics and age-matched controls were comparable (n = 6). Decreased vasodilation in diabetic group was observed when dose-response curves to Ilo (1 nM-0.1 microM) were realized in isolated hearts (-22 +/- 3.3% vs -46 +/- 3.9%, n = 6, p < 0.05). Secondly, dose-response curves to forskolin (FSK), an adenylate-cyclase activator, performed in hearts (1 nM-3 microM), and on PE preconstricted rings (10 pM-10 microM) of diabetics and age-matched controls were comparable. Finally, the effect of an activator of ATP sensitive potassium channels (KATP), cromakalim (CMK), was evaluated in coronary circulation (0.3 nM-3 microM) and in aortas (10 pM-10 microM). Decreased vasodilation to CMK was observed in diabetic hearts (-10.5 +/- 4.3 vs -30.1 +/- 2.8%, n = 6, p < 0.05). In conclusion, under our experimental conditions, diabetes affects selectively the coronary vasodilation to iloprost. This modification of vascular reactivity may be due to a decrease of KATP channels sensitivity but not to a decreased activity of adenylate-cyclase.
Bouchard
J F
JF
Faculté de pharmacie, Université de Montréal, Québec, Canada.
Dumont
E C
EC
Lamontagne
D
D
D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects; D019806:Cromakalim / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D016285:Iloprost / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000009:adverse effects; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D005576:Colforsin; D013311:Streptozocin; D000255:Adenosine Triphosphate; D000262:Adenylyl Cyclases; D016285:Iloprost