Hydrogen peroxide modulates angiotensin II-induced contraction of mesenteric arteries from streptozotocin-induced diabetic rats.
Hydrogen peroxide (H(2)O(2)) contributes in the regulation of vascular tone, especially in pathological states. The role of H(2)O(2) and superoxide anion free radicals in angiotensin II (Ang II)-induced contraction of diabetic tissues was examined with the aim of elucidating the underlying mechanisms. Isometric tension in response to various drug treatments was measured in isolated superior mesenteric arteries of streptozotocin (STZ)-induced diabetic WKY rats using the Mulvany wire myograph. Compared to the normal (euglycaemic) arteries, the Ang II-induced contraction was significantly reduced in diabetic arteries. Superoxide dismutase (SOD; converts superoxide to H(2)O(2)) significantly reduced the contraction in both types of arteries -- an effect abolished by catalase (H(2)O(2) scavenger), suggesting that the SOD effect was mediated by H(2)O(2). Treatment with catalase had no effect on the Ang II contraction in euglycaemic arteries, but it raised the contraction in diabetic arteries to euglycaemic levels. This increase was similar to that observed with diabetic arteries incubated with L-NAME. Combined catalase and L-NAME treatment further enhanced the contraction in diabetic arteries, suggesting that the catalase effect was not mediated by nitric oxide (NO). The catalase effect was abolished by indomethacin treatment. These results suggest that attenuation of Ang II-induced contraction in diabetic tissues is modulated by endogenous H(2)O(2), the scavenging of which unmasks an indomethacin-sensitive (and therefore cyclooxygenase product-mediated) Ang II-induced contraction.
Chin
L C
LC
Department of Pharmacology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
Achike
F I
FI
Mustafa
M R
MR
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011921:Rats, Inbred WKY; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; D000804:Angiotensin II; D013311:Streptozocin; D006861:Hydrogen Peroxide; D002374:Catalase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester