scholarly journals The GPR55 agonist lysophosphatidylinositol relaxes rat mesenteric resistance artery and induces Ca2+release in rat mesenteric artery endothelial cells

2015 ◽  
Vol 172 (12) ◽  
pp. 3043-3057 ◽  
Author(s):  
Y M AlSuleimani ◽  
C R Hiley

2017 ◽  
Vol 312 (4) ◽  
pp. H791-H799 ◽  
Author(s):  
Laura V. Gonzalez Bosc ◽  
Jessica M. Osmond ◽  
Wieslawa K. Giermakowska ◽  
Carolyn E. Pace ◽  
Jennifer L. Riggs ◽  
...  

Sleep apnea is a risk factor for cardiovascular disease, and intermittent hypoxia (IH, 20 episodes/h of 5% O2-5% CO2 for 7 h/day) to mimic sleep apnea increases blood pressure and impairs hydrogen sulfide (H2S)-induced vasodilation in rats. The enzyme that produces H2S, cystathionine γ-lyase (CSE), is decreased in rat mesenteric artery endothelial cells (EC) following in vivo IH exposure. In silico analysis identified putative nuclear factor of activated T cell (NFAT) binding sites in the CSE promoter. Therefore, we hypothesized that IH exposure reduces Ca2+ concentration ([Ca2+]) activation of calcineurin/NFAT to lower CSE expression and impair vasodilation. In cultured rat aortic EC, inhibiting calcineurin with cyclosporine A reduced CSE mRNA, CSE protein, and luciferase activity driven by a full-length but not a truncated CSE promoter. In male rats exposed to sham or IH conditions for 2 wk, [Ca2+] in EC in small mesenteric arteries from IH rats was lower than in EC from sham rat arteries (Δfura 2 ratio of fluorescence at 340 to 380 nm from Ca2+ free: IH = 0.05 ± 0.02, sham = 0.17 ± 0.03, P < 0.05), and fewer EC were NFATc3 nuclear positive in IH rat arteries than in sham rat arteries (IH = 13 ± 3, sham = 59 ± 11%, P < 0.05). H2S production was also lower in mesenteric tissue from IH rats vs. sham rats. Endothelium-dependent vasodilation to acetylcholine (ACh) was lower in mesenteric arteries from IH rats than in arteries from sham rats, and inhibiting CSE with β-cyanoalanine diminished ACh-induced vasodilation in arteries from sham but not IH rats but did not affect dilation to the H2S donor NaHS. Thus, IH lowers EC [Ca2+], NFAT activity, CSE expression and activity, and H2S production while inhibiting NFAT activation lowers CSE expression. The observations that IH exposure decreases NFATc3 activation and CSE-dependent vasodilation support a role for NFAT in regulating endothelial H2S production. NEW & NOTEWORTHY This study identifies the calcium-regulated transcription factor nuclear factor of activated T cells as a novel regulator of cystathionine γ-lyase (CSE). This pathway is basally active in mesenteric artery endothelial cells, but, after exposure to intermittent hypoxia to mimic sleep apnea, nuclear factor of activated T cells c3 nuclear translocation and CSE expression are decreased, concomitant with decreased CSE-dependent vasodilation.





Cell Calcium ◽  
2001 ◽  
Vol 30 (4) ◽  
pp. 261-267 ◽  
Author(s):  
H. Oishi ◽  
S. Budel ◽  
A. Schuster ◽  
N. Stergiopulos ◽  
J.-J. Meister ◽  
...  


2020 ◽  
Vol 11 ◽  
Author(s):  
Samuel N. Baldwin ◽  
Shaun L. Sandow ◽  
Gema Mondéjar-Parreño ◽  
Jennifer B. Stott ◽  
Iain A. Greenwood

Background and Purpose: Arterial diameter is dictated by the contractile state of the vascular smooth muscle cells (VSMCs), which is modulated by direct and indirect inputs from endothelial cells (ECs). Modulators of KCNQ-encoded kV7 channels have considerable impact on arterial diameter and these channels are known to be expressed in VSMCs but not yet defined in ECs. However, expression of kV7 channels in ECs would add an extra level of vascular control. This study aims to characterize the expression and function of KV7 channels within rat mesenteric artery ECs.Experimental Approach: In rat mesenteric artery, KCNQ transcript and KV7 channel protein expression were determined via RT-qPCR, immunocytochemistry, immunohistochemistry and immunoelectron microscopy. Wire myography was used to determine vascular reactivity.Key Results: KCNQ transcript was identified in isolated ECs and VSMCs. KV7.1, KV7.4 and KV7.5 protein expression was determined in both isolated EC and VSMC and in whole vessels. Removal of ECs attenuated vasorelaxation to two structurally different KV7.2-5 activators S-1 and ML213. KIR2 blockers ML133, and BaCl2 also attenuated S-1 or ML213-mediated vasorelaxation in an endothelium-dependent process. KV7 inhibition attenuated receptor-dependent nitric oxide (NO)-mediated vasorelaxation to carbachol, but had no impact on relaxation to the NO donor, SNP.Conclusion and Implications: In rat mesenteric artery ECs, KV7.4 and KV7.5 channels are expressed, functionally interact with endothelial KIR2.x channels and contribute to endogenous eNOS-mediated relaxation. This study identifies KV7 channels as novel functional channels within rat mesenteric ECs and suggests that these channels are involved in NO release from the endothelium of these vessels.



Life Sciences ◽  
1990 ◽  
Vol 46 (12) ◽  
pp. 881-884 ◽  
Author(s):  
Celso E. Gomez-Sanchez ◽  
Mark F. Foecking ◽  
Mary W. Ferris ◽  
Hiroko S. Hieda ◽  
Elise P. Gomez-Sanchez


1982 ◽  
Vol 23 (5) ◽  
pp. 783-789
Author(s):  
Hiromichi SUZUKI ◽  
Kazuoki KONDO ◽  
Michiko HANDA ◽  
Takao SARUTA


Life Sciences ◽  
2007 ◽  
Vol 80 (22) ◽  
pp. 2060-2066 ◽  
Author(s):  
Benzhi Cai ◽  
Dongmei Gong ◽  
Zhenwei Pan ◽  
Yu Liu ◽  
Hong Qian ◽  
...  




2005 ◽  
Vol 289 (5) ◽  
pp. H2234-H2243 ◽  
Author(s):  
Takayuki Matsumoto ◽  
Kentaro Wakabayashi ◽  
Tsuneo Kobayashi ◽  
Katsuo Kamata

To assess the functional change in adenylyl cyclases (AC) associated with the diabetic state, we investigated AC-mediated relaxations and cAMP production in mesenteric arteries from rats with streptozotocin (STZ)-induced diabetes. The relaxations induced by the water-soluble forskolin (FSK) analog NKH477, which is a putative AC5 activator, but not by the β-adrenoceptor agonist isoproterenol (Iso) and the AC activator FSK, were reduced in intact diabetic mesenteric artery. In diabetic rats, however, Iso-, FSK-, and NKH477-induced relaxations were attenuated in the presence of inhibitors of nitric oxide synthase and cyclooxygenase. To exclude the influence of phosphodiesterase (PDE), we also examined the relaxations induced by several AC activators in the presence of 3-isobutyl-1-methylxanthine (IBMX; a PDE inhibitor). Under these conditions, the relaxation induced by Iso was greatly impaired in STZ-diabetic rats. This Iso-induced relaxation was significantly attenuated by pretreatment with SQ-22536, an AC inhibitor, in mesenteric rings from age-matched controls but not in those from STZ-diabetic rats. Under the same conditions, the relaxations induced by FSK or NKH477 were impaired in STZ-diabetic rats. Neither FSK- nor A-23187 (a Ca2+ ionophore)-induced cAMP production was significantly different between diabetics and controls. However, cAMP production induced by Iso or NKH477 was significantly impaired in diabetic mesenteric arteries. Expression of mRNAs and proteins for AC5/6 was lower in diabetic mesenteric arteries than in controls. These results suggest that AC-mediated relaxation is impaired in the STZ-diabetic rat mesenteric artery, perhaps reflecting a reduction in AC5/6 activity.



1997 ◽  
Vol 120 (7) ◽  
pp. 1328-1334 ◽  
Author(s):  
Mitsuhiro Fukao ◽  
Yuichi Hattori ◽  
Morio Kanno ◽  
Ichiro Sakuma ◽  
Akira Kitabatake


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