Preferential reduction in vascular responses to endothelin-1 in rats with streptozotocin-induced diabetes.
The effects of vasodepressor (acetylcholine and bradykinin) and pressor [electrical stimulation of the spinal sympathetic outflow, norepinephrine and endothelin-1 (ET-1)] stimuli were determined in rats with 2- and 5-week untreated streptozotocin-induced diabetes (blood glucose 400 and >500 mg/dl, respectively). In pentobarbital-anesthetized animals, the hypotensive response to an intravenous dose of acetylcholine or bradykinin was unaffected in animals treated for 2 weeks with streptozotocin but was significantly reduced (22% and 48%, respectively) after 5 weeks. However, the pressor responses to ET-1 were significantly decreased in animals that had been given streptozotocin 2 (38%) and 5 (45%) weeks previously. In contrast, the vasoconstrictor effects of electrical stimulation of the spinal cord outflow and norepinephrine were significantly inhibited (47% and 30%, respectively) at 5 weeks, but not at 2 weeks, after streptozotocin administration. These results indicate that, in untreated streptozotocin diabetes, a substantial impairment of vascular reactivity to ET-1 appears more rapidly than inhibition of the pressor responses to endogenous and exogenous norepinephrine or to vasodilator substances that require integrity of vascular endothelial cell function to produce their normal effects.
Guillon
J M
JM
Rhône-Poulenc Rorer, Research Center of Vitry-Alfortville, Vitry sur Seine, France.
Thiry
C
C
Roach
A G
AG
Cavero
I
I
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004558:Electric Stimulation; D019332:Endothelin-1 / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001786:Blood Glucose; D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D000109:Acetylcholine; D001920:Bradykinin; D009638:Norepinephrine