title: The effect of streptozotocin-induced diabetes on the EDHF-type relaxation and cardiac function in rats.
abstract: The endothelium-derived hyperpolarizing factor (EDHF) response is a critical for the functioning of small blood vessels. We investigated the effect of streptozotocin-induced diabetes on the EDHF response and its possible role in the regulation of cardiac function. The vasorelaxant response to ACh- or NS309- (direct opener endothelial small- (SKCa)- and intermediate-conductance (IKCa) calcium-activated potassium channels; main components of EDHF response) were measured in pressurized mesenteric arteries (diameter 300-350 μm). The response to 1 μM ACh was reduced in diabetes (84.8 ± 2.8% control vs 22.5 ± 5.8% diabetics; n ⩾ 8; P < 0.001). NS309 (1 μM) relaxations were also decreased in diabetic arteries (78.5 ± 8.7% control vs 32.1 ± 5.8% diabetics; n ⩾ 5; P < 0.001). SKCa and IKCa-mediated EDHF relaxations in response ACh or NS309 were also significantly reduced by diabetes. Ruthenium red, RuR, a blocker of TRP channels, strongly depress the response to ACh and NS309 in control and diabetic arteries. RuR decreased SKCa and IKCa-mediated EDHF vasodilatation in response to NS309 but not to ACh. An elevation in systolic blood pressure was observed in diabetic animals. ECG recording of control hearts showed shortening of PR interval. RuR reduced PR interval and R wave amplitude in diabetic hearts. In conclusion, the reduced EDHF-type relaxations in STZ-induced diabetes is due impairment of KCa channels function. TRP channels possibly contribute to EDHF vasodilatation via direct opening of endothelial KCa. It is possible that EDHF and TRP channels contribute to the regulation of cardiac function and therefore can be considered as therapeutic targets to improve cardiovascular complications of diabetes.
authors: Pharmacology and Toxicology Department, Faculty of Pharmacy, Aleppo University, Syria.
authors: Mais
authors: M
authors: Absi
authors: Pharmacology and Toxicology Department, Faculty of Pharmacy, Aleppo University, Syria.
authors: Hani
authors: H
authors: Oso
authors: Faculty of Sciences, Zoology Department, Aleppo University, Syria.
authors: Marwan
authors: M
authors: Khattab
keywords: Diabetes; EDHF; KCa channels; TRP channels