Endothelium-Derived Relaxing Factor–Mediated Vasodilation in Mouse Mesenteric Vascular Beds

Abstract

Abstract. The endothelium in rat mesenteric vascular beds has been demonstrated to regulate vascular tone by releasing mainly endothelium-derived hyperpolarizing factor (EDHF), which is involved in the activation of K + channels and gap-junctions. However, it is unclear whether the endothelial system in mouse resistance arteries contributes to regulation of the vascular tone. The present study was designed to investigate the role of the endothelium using acetylcholine and A23187 (Ca 2+ ionophore) in mesenteric vascular beds isolated from male C57BL/6 mice and perfused with Krebs solution to measure perfusion pressure. In preparations with active tone produced by methoxamine in the presence of guanethidine, injections of acetylcholine, A23187, and sodium nitroprusside (SNP) caused a concentration-dependent decrease in perfusion pressure due to vasodilation. The vasodilator responses to acetylcholine and A23187, but not SNP, were abolished by endothelium dysfunction and significantly inhibited by N ω -nitro-L-arginine methyl ester (nitric oxide synthase inhibitor) and tetraethylammonium (K + -channel inhibitor) but not glibenclamide (ATP-sensitive K + -channel inhibitor). Indomethacin (cyclooxygenase inhibitor) significantly blunted only A23187-induced vasodilation, while 18α-glycyrrhetinic acid (gap-junction inhibitor) attenuated only acetylcholine-induced vasodilation. These results suggest that the endothelium in mouse mesenteric arteries regulates vascular tone by prostanoids, EDHF, and partially by nitric oxide, different from the endothelium of rat mesenteric arteries.

Role of CYP1A1 in Modulating the Vascular and Blood Pressure Benefits of Omega-3 Polyunsaturated Fatty Acids

“…Although CYP1A1 KO mice on an n-6 PUFA diet exhibited a normal dilation response to ACh, none of it was NO-dependent, suggesting that in KO mice there is a loss of NO and an increase in the contribution from compensatory mechanisms. We did not investigate the mediators of ACh dilation in CYP1A1 KO mice on an n-6 PUFA diet; however, increases in endothelial-derived hyperpolarizing factors via AA metabolism represent likely candidates (Hercule et al, 2009;Fujiwara et al, 2012).…”

Na⁺/Ca²⁺ Exchanger 1 Transgenic Mice Display Increased Relaxation in the Distal Colon

“…The EFS-induced relaxation is thought to be mediated by NANC signaling [28], which is also confirmed in the present study. Main mechanisms of the EFS-induced relaxation are mediated through both CO and NO/sGC/cGMP/PKG [30,31,32] and PACAP/VIP/cAMP/PKA signaling [33,34]. In fact, in the current study, many related inhibitors of these signaling pathways partially inhibited the EFS-induced relaxation in the WT colon.…”

“…PACAP and VIP cause hyperpolarization and relaxation through an apamin-sensitive small conductance Ca 2+ -activated K + channel [34]. As shown in figure 6c and d, Tg exhibited magnitudes of PACAP27- and VIP-induced relaxation similar to those of WT.…”

Vascular Reactivity in Newly-Formed and Mature Arterialized Collateral Capillaries

“…Thus, investigating dysfunction in the prevalent endothelial-derived relaxing factor (EDRF) production pathways within the endothelium may reveal contributors to functional vasodilation impairment, as demonstrated at day seven. EDRFs primarily describe three vasodilatory signals that originate from the endothelium and include nitric oxide (NO), prostaglandin I 2 (PGI 2 ), and endothelium-derived hyperpolarizing factor (EDHF) (24). EDHF is more critical in smaller resistance vessels such as arterialized capillaries, while in larger preexisting collaterals, NO production may be more prevalent; however, PGI 2 mediates endothelial-dependent vasodilation in both the smaller and larger arterial vessels (22,73).…”

“…This process utilizes the prostaglandin pathway, which can be inhibited by indomethacin downstream of AA activation to analyze the prostaglandin pathway more exclusively (56,61). Indomethacin is a non-steroidal antiinflammatory drug (NSAID), which inhibits cyclooxygenase (COX) and prostaglandin synthesis (24,71).…”