scholarly journals Apelin Does Not Impair Coronary Artery Relaxation Mediated by Nitric Oxide-Induced Activation of BKCa Channels

2021 ◽  
Vol 12 ◽  
Author(s):  
Amreen Mughal ◽  
Chengwen Sun ◽  
Stephen T. O’Rourke
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Coronary Arteries ◽  
Muscle Cells ◽  
Inhibitory Effect ◽  
Receptor Signaling ◽  
Patch Clamp Recording ◽  
Bkca Channels ◽  
Channel Function

Apelin-APJ receptor signaling regulates vascular tone in cerebral and peripheral arteries. We recently reported that apelin inhibits BKCa channel function in cerebral arteries, resulting in impaired endothelium-dependent relaxations. In contrast, apelin causes endothelium-dependent relaxation of coronary arteries. However, the effects of apelin on BKCa channel function in coronary arterial myocytes have not yet been explored. We hypothesized that apelin-APJ receptor signaling does not have an inhibitory effect on coronary arterial BKCa channels and hence does not alter nitric oxide (NO)-dependent relaxation of coronary arteries. Patch clamp recording was used to measure whole cell K+ currents in freshly isolated coronary smooth muscle cells. Apelin had no effect on the increases in current density in response to membrane depolarization or to NS1619 (a BKCa channel opener). Moreover, apelin did not inhibit NO/cGMP-dependent relaxations that required activation of BKCa channels in isolated coronary arteries. Apelin-APJ receptor signaling caused a marked increase in intracellular Ca2+ levels in coronary arterial smooth muscle cells, but failed to activate PI3-kinase to increase phosphorylation of Akt protein. Collectively, these data provide mechanistic evidence that apelin has no inhibitory effects on BKCa channel function in coronary arteries. The lack of inhibitory effect on BKCa channels makes it unlikely that activation of APJ receptors in coronary arteries would adversely affect coronary flow by creating a vasoconstrictive environment. It can be expected that apelin or other APJ receptor agonists in development will not interfere with the vasodilator effects of endogenous BKCa channel openers.

Nitric oxide inhibits Ca2+ mobilization through cADP-ribose signaling in coronary arterial smooth muscle cells

2000 ◽  
Vol 279 (3) ◽  
pp. H873-H881 ◽  
Author(s):  
Jiang-Zhou Yu ◽  
David X. Zhang ◽  
Ai-Ping Zou ◽  
William B. Campbell ◽  
Pin-Lan Li
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Inhibitory Effect ◽  
Cyclase Activity ◽  
Arterial Smooth Muscle ◽  
Adp Ribosyl Cyclase ◽  
Intracellular Ca ◽  
Arterial Smooth Muscle Cells

The present study was designed to determine whether the cADP-ribose-mediated Ca2+ signaling is involved in the inhibitory effect of nitric oxide (NO) on intracellular Ca2+ mobilization. With the use of fluorescent microscopic spectrometry, cADP-ribose-induced Ca2+ release from sarcoplasmic reticulum (SR) of bovine coronary arterial smooth muscle cells (CASMCs) was determined. In the α-toxin-permeabilized primary cultures of CASMCs, cADP-ribose (5 μM) produced a rapid Ca2+ release, which was completely blocked by pretreatment of cells with the cADP-ribose antagonist 8-bromo-cADP-ribose (8-Br-cADPR). In intact fura 2-loaded CASMCs, 80 mM KCl was added to depolarize the cells and increase intracellular Ca2+ concentration ([Ca2+]i). Sodium nitroprusside (SNP), an NO donor, produced a concentration-dependent inhibition of the KCl-induced increase in [Ca2+]i, but it had no effect on the U-46619-induced increase in [Ca2+]i. In the presence of 8-Br-cADPR (100 μM) and ryanodine (10 μM), the inhibitory effect of SNP was markedly attenuated. HPLC analyses showed that CASMCs expressed the ADP-ribosyl cyclase activity, and SNP (1–100 μM) significantly reduced the ADP-ribosyl cyclase activity in a concentration-dependent manner. The effect of SNP was completely blocked by addition of 10 μM oxygenated hemoglobin. We conclude that ADP-ribosyl cyclase is present in CASMCs, and NO may decrease [Ca2+]i by inhibition of cADP-ribose-induced Ca2+ mobilization.

Ebselen reduces nitration and restores voltage-gated potassium channel function in small coronary arteries of diabetic rats

2007 ◽  
Vol 293 (4) ◽  
pp. H2231-H2237 ◽  
Author(s):  
Aaron H. Bubolz ◽  
Qingping Wu ◽  
Brandon T. Larsen ◽  
David D. Gutterman ◽  
Yanping Liu
Keyword(s):  
Diabetes Mellitus ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Coronary Arteries ◽  
Nitrosative Stress ◽  
Muscle Cells ◽  
Diabetic Rats ◽  
Causative Role ◽  
Α Subunit ◽  
Channel Function

Small coronary arteries (SCA) from diabetic rats exhibit enhanced peroxynitrite (ONOO−) formation and concurrent impairment of voltage-dependent potassium (Kv) channel function. However, it is unclear whether ONOO− plays a causative role in this impairment. We hypothesized that functional loss of Kv channels in coronary smooth muscle cells (SMC) in diabetes is due to ONOO− with subsequent tyrosine nitration of Kv channel proteins. Diabetic rats and nondiabetic controls were treated with or without ebselen (Eb) for 4 wk. SCA were prepared for immunohistochemistry (IHC), immunoprecipitation (IP) followed by Western blot (WB), videomicroscopy, and patch-clamp analysis. IHC revealed excess ONOO− in SCA from diabetic rats. IP and WB revealed elevated nitration of the Kv1.2 α-subunit and reduced Kv1.2 protein expression in diabetic rats. Each of these changes was improved in Eb-treated rats. Protein nitration and Kv1.5 expression were unchanged in SCA from diabetic rats. Forskolin, a direct cAMP activator that induces Kv1 channel activity, dilated SCA from nondiabetic rats in a correolide (Cor; a selective Kv1 channel blocker)-sensitive fashion. Cor did not alter the reduced dilation to forskolin in diabetic rats; however, Eb partially restored the Cor-sensitive component of dilation. Basal Kv current density and response to forskolin were improved in smooth muscle cells from Eb-treated DM rats. We conclude that enhanced nitrosative stress in diabetes mellitus contributes to Kv1 channel dysfunction in the coronary microcirculation. Eb may be beneficial for the therapeutic treatment of vascular complications in diabetes mellitus.

scholarly journals Leptin Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by Angiotensin II through Nitric Oxide-Dependent Mechanisms

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Amaia Rodríguez ◽  
Javier Gómez-Ambrosi ◽  
Victoria Catalán ◽  
Ana Fortuño ◽  
Gema Frühbeck
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Proliferative Response ◽  
Muscle Cells ◽  
Inhibitory Effect ◽  
No Production ◽  
Ang Ii

Objective. This study was designed to investigate whether leptin modifies angiotensin (Ang) II-induced proliferation of aortic vascular smooth muscle cells (VSMCs) from 10-week-old male Wistar and spontaneously hypertensive rats (SHR), and the possible role of nitric oxide (NO).Methods. NO and NO synthase (NOS) activity were assessed by the Griess and3H-arginine/citrulline conversion assays, respectively. Inducible NOS (iNOS) and NADPH oxidase subutnit Nox2 expression was determined by Western-blot. The proliferative responses to Ang II were evaluated through enzymatic methods.Results. Leptin inhibited the Ang II-induced proliferative response of VSMCs from control rats. This inhibitory effect of leptin was abolished by NOS inhibitor, NMMA, and iNOS selective inhibitor, L-NIL, and was not observed in leptin receptor-deficientfa/farats. SHR showed increased serum leptin concentrations and lipid peroxidation. Despite a similar leptin-induced iNOS up-regulation, VSMCs from SHR showed an impaired NOS activity and NO production induced by leptin, and an increased basal Nox2 expression. The inhibitory effect of leptin on Ang II-induced VSMC proliferation was attenuated.Conclusion. Leptin blocks the proliferative response to Ang II through NO-dependent mechanisms. The attenuation of this inhibitory effect of leptin in spontaneous hypertension appears to be due to a reduced NO bioavailability in VSMCs.

Thrombin Prevents the Expression of Inducible Nitric Oxide Synthase in Vascular Smooth Muscle Cells by a Proteolytically-Activated Thrombin Receptor

1995 ◽  
Vol 74 (03) ◽  
pp. 980-986 ◽  
Author(s):  
Valérie B Schini-Kerth ◽  
Beate Fißithaler ◽  
Thomas T Andersen ◽  
John W Fenton ◽  
Paul M Vanhoutte ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Inducible Nitric Oxide Synthase ◽  
Muscle Cells ◽  
Thrombin Receptor ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

SummaryProteolytically active forms of thrombin (α- and γ-thrombin) and thrombin receptor peptides inhibited the release of nitrite, a stable endproduct of nitric oxide, evoked by interleukin-1 β(IL-1 β) in cultured vascular smooth muscle cells while proteolytically inactive forms [D-Phe-Pro-Arg chloromethyl ketone-α-thrombin (PPACK-α- thrombin) and diisopropylphosphoryl-α-thrombin (DIP-α-thrombin)] had either no or only minimal inhibitory effects. Under bioassay conditions, perfusates from columns containing IL-1 β-activated vascular smooth muscle cells or cells treated with IL-1βplus PPACK-α-thrombin relaxed detector blood vessels. These relaxations were abolished by the inhibitor of nitric oxide synthesis, NG-nitro-L arginine. No relaxations were obtained with untreated cells or IL-1 β-treated cells in the presence of α-thrombin. The expression of inducible nitric oxide synthase mRNA and protein in vascular smooth muscle cells by IL-1 β was impaired by α-thrombin. These results demonstrate that thrombin regulates the expression of the inducible nitric oxide synthase at a transcriptional level via the proteolytic activation of the thrombin receptor in vascular smooth muscle cells

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