Role of protein kinase C in electrical-stimulation-induced neuronal nitric oxide release in mesenteric arteries from hypertensive rats

2000 ◽  
Vol 99 (4) ◽  
pp. 277-283 ◽  
Author(s):  
Jesús MARÍN ◽  
Mercedes FERRER ◽  
Gloria BALFAGÓN
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
No Synthase ◽  
Mesenteric Arteries ◽  
Protein Synthesis Inhibitor ◽  
Hypertensive Rats ◽  
Wky Rats ◽  
Kinase C ◽  
No Release

This study examines the influence of hypertension on neuronal nitric oxide (NO) release and its modulation by protein kinase C (PKC). For this purpose, mesenteric segments without endothelium were obtained from Wistar–Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs), and neurogenic NO release induced by electrical field stimulation (EFS) was examined in these segments. EFS induced frequency-dependent contractions. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and the sensorial neurotoxin capsaicin increased EFS-induced contractions in SHR segments, but did not affect these contractions in segments from WKY rats. In segments from SHRs, the increase in EFS-induced response by capsaicin was further increased by the combination of capsaicin and L-NAME. EFS-induced contractions in SHR arteries were unaltered by the protein synthesis inhibitor cycloheximide or by 2-amine-5,6-dihydro-6-methyl-4H-1,3-tiazine (AMT), an inhibitor of inducible NO synthase, and increased by the guanylate cyclase inhibitor Methylene Blue. In these arteries, capsaicin plus the PKC inhibitor calphostin C increased the contractions elicited by EFS; the addition of L-NAME did not affect this increase. Phorbol 12,13-dibutyrate (PDBu) did not modify the response to EFS in these arteries pretreated with capsaicin, although a combination of PDBu and L-NAME was effective. These results indicate that, in mesenteric arteries, EFS induces the release of NO from perivascular nitrergic nerves and of neuropeptides from sensory nerves, but only in hypertensive rats. The NO released is synthesized by constitutive neuronal NO synthase in a manner that is positively modulated by PKC, an enzyme that seems to be activated in hypertension.

Dexamethasone decreases neuronal nitric oxide release in mesenteric arteries from hypertensive rats through decreased protein kinase C activation

2009 ◽  
Vol 117 (8) ◽  
pp. 305-312 ◽  
Author(s):  
Rosa Aras-López ◽  
Fabiano E. Xavier ◽  
Mercedes Ferrer ◽  
Gloria Balfagón
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Glucocorticoid Receptors ◽  
Electrical Field Stimulation ◽  
Mesenteric Arteries ◽  
Hypertensive Rats ◽  
Pkc Inhibitor ◽  
Kinase C ◽  
No Release ◽  
Wistar Kyoto

Neuronal NO plays a functional role in many vascular tissues, including MAs (mesenteric arteries). Glucocorticoids alter NO release from endothelium and the CNS (central nervous system), but no results from peripheral innervation have been reported. In the present study we investigated the effects of dexamethasone on EFS (electrical field stimulation)-induced NO release in MAs from WKY (Wistar–Kyoto) rats and SHRs (spontaneously hypertensive rats) and the role of PKC (protein kinase C) in this response. In endothelium-denuded MAs, L-NAME (NG-nitro-L-arginine methyl ester) increased the contractile response to EFS only in segments from SHRs. EFS-induced contraction was reduced by 1 μmol/l dexamethasone in segments from SHRs, but not WKY rats, and this effect was abolished in the presence of dexamethasone. EFS induced a tetrodotoxin-resistant NO release in WKY rat MAs, which remained unchanged by 1 μmol/l dexamethasone. In SHR MAs, dexamethasone decreased basal and EFS-induced neuronal NO release, and this decrease was prevented by the glucocorticoid receptor antagonist mifepristone. Dexamethasone did not affect nNOS [neuronal NOS (NO synthase)] expression in either strain. In SHR MAs, incubation with calphostin C (a non-selective PKC inhibitor), Gö6983 (a classic PKC δ and ζ inhibitor), LY379196 (a PKCβ inhibitor) or PKCζ-PI (PKCζ pseudosubstrate inhibitor) decreased both basal and EFS-induced neuronal NO release. Additionally, PKC activity was reduced by dexamethasone. The PKC inhibitor-induced reduction in NO release was unaffected by dexamethasone. In conclusion, results obtained in the present study indicate that PKC activity positively modulates the neuronal NO release in MAs from SHRs. They also reveal that by PKC inhibition, through activation of glucocorticoid receptors, dexamethasone reduces neuronal NO release in these arteries.

scholarly journals Protein kinase C activation increases endothelial nitric oxide release in mesenteric arteries from orchidectomized rats

2007 ◽  
Vol 192 (1) ◽  
pp. 189-197 ◽  
Author(s):  
Javier Blanco-Rivero ◽  
Ana Sagredo ◽  
Gloria Balfagón ◽  
Mercedes Ferrer
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase C ◽  
Mesenteric Arteries ◽  
Enos Expression ◽  
Pkc Inhibitor ◽  
Calphostin C ◽  
Kinase C ◽  
No Release ◽  
Male Sex ◽  
Endothelial Nitric Oxide

The aim of the present study was to assess the effect of endogenous male sex hormones on endothelial nitric oxide synthase (eNOS) expression, release and function of the endothelial nitric oxide (NO), as well as to assess the regulatory action of protein kinase C (PKC) on acetylcholine (ACh)-induced endothelial NO release. For this purpose, superior mesenteric arteries from control and orchidectomized male Sprague–Dawley rats were used. eNOS expression and basal-and ACh-induced NO release were similar in arteries from both groups of rats. Orchidectomy decreased the vasodilator effect induced by ACh but did not alter that induced by sodium nitroprusside (SNP). The superoxide anion scavenger, superoxide dismutase (SOD), or the membrane-permeable mimetic of SOD, tempol, only enhanced ACh-induced relaxation in arteries from orchidectomized rats. ACh-induced TXA2 formation was higher in arteries from orchidectomized than from control rats. Neither the PKC activator, phorbol 12,13-dibutyrate (PDBu), nor the non-selective PKC inhibitor, calphostin C, modified basal- or ACh-induced NO release in arteries from control rats. In arteries from orchidectomized rats, basal- and ACh-induced endothelial NO release were increased by PDBu but decreased by calphostin C. Both Gö6976, a PKC inhibitor that is partially selective for conventional PKC isoforms, as well as PKCζ pseudosubstrate inhibitor (PKCζ-PI) decreased both basal- and ACh-induced NO release in arteries from orchidectomized rats. Neither PDBu nor calphostin C modified the vasodilator response induced by ACh in arteries from control rats. In segments from orchidectomized rats, PDBu enhanced the ACh-induced response, but this response was not modified by calphostin C, Gö6976 or PKCζ-PI. The vasodilator response induced by SNP was not altered by the PKC activators or inhibitors in any artery from either group. These results show that endogenous male sex hormone deprivation does not affect the eNOS expression or the endothelial NO release induced by ACh, but does decrease the vasodilator action of ACh, by increasing NO metabolism and TXA2 formation. In addition, PKC seems to modulate eNOS activity only in mesenteric arteries from orchidectomized rats, in which conventional and PKCζ isoforms are involved in the positive regulation of eNOS.

Diabetes alters neuronal nitric oxide release from rat mesenteric arteries. Role of protein kinase C

Life Sciences ◽  
1999 ◽  
Vol 66 (4) ◽  
pp. 337-345 ◽  
Author(s):  
Mercedes Ferrer ◽  
Jesús Marín ◽  
Gloria Balfagón
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Mesenteric Arteries ◽  
Nitric Oxide Release ◽  
Kinase C

Nitric oxide synthase-inhibition hypertension is associated with altered endothelial cyclooxygenase function

2004 ◽  
Vol 287 (6) ◽  
pp. H2394-H2401 ◽  
Author(s):  
Ian N. Bratz ◽  
Nancy L. Kanagy
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
No Synthase ◽  
Mesenteric Arteries ◽  
No Production ◽  
Hypertensive Rats ◽  
Maximum Tension ◽  
No Release ◽  
Vascular Sensitivity ◽  
Oxide Synthase

We reported previously that endothelium-intact superior mesenteric arteries (SMA) from Nω-nitro-l-arginine (l-NNA)-treated hypertensive rats (LHR) contract more to norepinephrine (NE) than SMA from control rats. Others have shown that nitric oxide (NO) synthase (NOS) inhibition increases cyclooxygenase (COX) function and expression. We hypothesized that augmented vascular sensitivity to NE in LHR arteries is caused by decreased NOS-induced dilation and increased COX product-induced constriction. We observed that the EC50 for NE is lower in LHR SMA compared with control SMA (control −6.37 ± 0.04, LHR −7.89 ± 0.09 log mol/l; P < 0.05). Endothelium removal lowered the EC50 (control −7.95 ± 0.11, LHR −8.44 ± 0.13 log mol/l; P < 0.05) and increased maximum tension in control (control 1,036 ± 38 vs. 893 ± 21 mg; P < 0.05) but not LHR (928 ± 30 vs. 1,066 ± 31 mg) SMA. Thus augmented NE sensitivity in LHR SMA depends largely on decreased endothelial dilation. NOS inhibition (l-NNA, 10−4 mol/l) increased maximum tension and EC50 in control arteries but not in LHR arteries. In contrast, COX inhibition decreased maximum tension in control arteries, suggesting that COX products augment contraction. Indomethacin did not affect NE-induced contraction in l-NNA-treated or denuded arteries. In control SMA loaded with the fluorescent NO indicator 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate, indomethacin increased and l-NNA decreased NO release. Therefore, COX products appear to inhibit NO production to augment NE-induced contraction. With chronic NOS inhibition, this modulating influence is greatly diminished. Thus, in NOS-inhibition hypertension, decreased activity of both COX and NOS pathways profoundly disrupts endothelial modulation of contraction.

Oxidative stress in diabetes-induced endothelial dysfunction involvement of nitric oxide and protein kinase C

2003 ◽  
Vol 35 (6) ◽  
pp. 683-694 ◽  
Author(s):  
Flavia Pricci ◽  
Gaetano Leto ◽  
Lorena Amadio ◽  
Carla Iacobini ◽  
Samantha Cordone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Endothelial Dysfunction ◽  
Kinase C

Altered Cardiac Endothelin Receptors and Protein Kinase C in Deoxycorticosterone-Salt Hypertensive Rats

2000 ◽  
Vol 32 (4) ◽  
pp. 665-676 ◽  
Author(s):  
Jeannette Fareh ◽  
Rhian M Touyz ◽  
Ernesto L Schiffrin ◽  
Gaétan Thibault
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Endothelin Receptors ◽  
Hypertensive Rats ◽  
Kinase C

Gene‐gene interactions in the protein kinase C/endothelial nitric oxide synthase axis impact the hypotensive effects of propofol

2021 ◽  
Author(s):  
Gustavo H. Oliveira‐Paula ◽  
Daniela A. Pereira ◽  
Lucas C. Pinheiro ◽  
Graziele C. Ferreira ◽  
Waynice N. Paula‐Garcia ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Gene Interactions ◽  
Kinase C ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide
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