Enhanced contractility of small mesenteric arteries from diabetic mice to phenylephrine was endothelium-dependent and involved elevated reactive oxygen species and cyclooxygenase activity.
In a diabetic mouse model, enhanced vascular reactivity in small mesenteric arteries is driven by endothelial reactive oxygen species and cyclooxygenase/thromboxane pathways rather than eNOS/NO dysfunction.
Vascular reactivity to the alpha-adrenoceptor agonist phenylephrine (PE) was enhanced in small mesenteric arteries (SMA) from diabetic (db/db) mice under both high and low in vitro oxygen conditions. Mechanical removal of the endothelium significantly attenuated the enhanced vascular reactivity of SMA from db/db mice. Acute incubation of the SMA with sepiapterin, a precursor of tetrahydrobiopterin, and N(omega)-nitro L-arginine (L-NA), an inhibitor of nitric oxide (NO) synthase (NOS), resulted in no significant change in the enhanced vascular reactivity to PE in db/db mice. Endothelial nitric oxide synthase (eNOS) mRNA and protein levels in SMA were not different between db/+ and db/db mice. Acute incubation of SMA with a combination of polyethylene glycol superoxide dismutase and catalase significantly reduced the enhanced contraction to PE in db/db mice. There were higher levels of malondialdehyde, a marker of lipid peroxidation and basal superoxide as measured by dihydroethidium staining, in SMA from db/db mice compared to db/+ mice. Acute incubation with indomethacin, a nonselective inhibitor of cyclooxygenase, SQ 29548, a selective thromboxane receptor antagonist and furegrelate, a thromboxane synthesis inhibitor, significantly attenuated the enhanced contraction to PE in SMA from db/db mice. This study demonstrates that the enhanced contractility of SMA from db/db mice to PE was endothelium dependent and involves elevated reactive oxygen species, cyclooxygenase activity and thromboxane synthesis, but not changes in the eNOS/NO pathway.
Pannirselvam et al. (Tue,) conducted a other in Diabetes (animal model). Diabetic state (db/db mice) vs. Control (db/+) mice was evaluated on Vascular reactivity to phenylephrine. Enhanced contractility of small mesenteric arteries from diabetic mice to phenylephrine was endothelium-dependent and involved elevated reactive oxygen species and cyclooxygenase activity.