Nitric Oxide In Mesenteric Artery Research Articles

Mechanisms underlying the relaxation by A484954, a eukaryotic elongation factor 2 kinase inhibitor, in rat isolated mesenteric artery

Eukaryotic elongation factor 2 kinase (eEF2K) is a calmodulin-related protein kinase which regulates protein translation. A484954 is an inhibitor of eEF2K. In the present study, we investigated the acute effects of A484954 on contractility of isolated blood vessels. Isometric contraction of rat isolated aorta and main branch of superior mesenteric artery (MA) was measured. Expression of an inward rectifier K+ (Kir) channel subtype mRNA and protein was examined. A484954 caused relaxation in endothelium-intact [E (+)] and -denuded [E (−)] aorta or MA precontracted with noradrenaline (NA). The relaxation was higher in MA than aorta. The relaxation was partially inhibited by a nitric oxide (NO) synthase inhibitor, NG-nitro-l-arginine methyl ester (300 μM) in E (+) MA. The relaxation was significantly smaller in MA precontracted with high K+ than NA. The A484954-induced relaxation was significantly inhibited by a Kir channel blocker, BaCl2 (1 mM) compared with vehicle control in E (−) MA. Expression of Kir2.2 mRNA and protein was significantly higher in MA than aorta. We for the first time revealed that A484954 induces relaxation through opening smooth muscle Kir (Kir2.2) channel and through endothelium-derived NO in MA.

Upregulation of endothelium-derived hyperpolarizing factor compensates for the loss of nitric oxide in mesenteric arteries of dahl salt-sensitive hypertensive rats

This study was designed to determine whether a high-salt diet would alter endothelial function and, if so, the relative contributions of endothelium-derived hyperpolarizing factor (EDHF) and nitric oxide (NO) to any changes in vasomotor responses. Male Dahl salt-sensitive (DS) rats were given either a high-salt diet (8% NaCl, DS-H) or a low-salt diet (0.4% NaCl, DS-L) for 6 weeks. Membrane potentials and contractile responses were recorded from the isolated superior mesenteric arteries. After salt loading, DS-H developed hypertension, while DS-L remained normotensive. No difference was found in acetylcholine (ACh)-induced, endothelium-dependent relaxation between the groups. However, after treatment with indomethacin and NO synthase inhibitor, EDHF-like relaxation was significantly greater in DS-H than in DS-L. In contrast, NO-mediated relaxation was significantly smaller in DS-Hthan in DS-L. Iberiotoxin (IbTx), a specific blocker of large-conductance calcium-dependent potassium (BKCa) channels, attenuated EDHF-like relaxation in DS-H but not in DS-L. IbTx marginally inhibited EDHF-mediated hyperpolarization only in DS-H. Endothelium-independent relaxation in response to sodium nitroprusside or levcromakalim was similar in both groups. In conclusion, EDHF-like relaxation is upregulated through the activation of BKCa channels in the mesenteric arteries of DS-H. As the overall relaxation in response to ACh did not differ between the groups, the upregulation of EDHF appears to compensate for the loss of NO in the mesenteric arteries of DS-H.