Examinando por Autor "Salaices, Mercedes"

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Endothelial Modulation of Ouabain-lnduced Contraction and Sodium Pump Activity in Aortas of Normotensive Wystar-Kyoto and Spontaneously Hypertensive Rats
(Karger Publishers, 1996) Ponte, Ana; Marín, Jesús; Arribas, Silvia; González-Carnicero, Rita; Barrús, M Teresa; Salaices, Mercedes; Sánchez-Ferrer, Carlos F
The influence of vascular endothelium on ouabain-induced contractions and sodium pump activity in aortic segments of Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR) was analyzed. De-endothelialization increased and reduced ouabain-induced contractions in WKY and SHR segments, respectively. The effects of de-endothelialization were not reproduced by pretreatment of the segments with NG-nitro-L-arginine methyl ester, indo-methacin, or 5, 8, 11, 14-eicosatetraenoic acid, acetyl salicylic acid, dazoxiben, phosphoramidon, BQ-123, or superoxide dismutase. Bioassay experiments suggest that ouabain releases a diffusible factor from endothelial cells that inhibits or facilitates digitalis-induced contractions in WKY and SHR segments, respectively. In a potassium-free solution, potassium-induced relaxation in segments of both strains was abolished by ouabain in de-endothelialized aortas and reduced in intact ones. Ouabain-sensitive 86Rb+ uptake was significantly reduced by de-endothelialization both in WKY and in SHR. These results suggest that the vascular endothelium of WKY and SHR aortas releases a diffusible factor that stimulates the sodium pump and/or protects it from ouabain blockade. Ouabain also releases a diffusible endothelium-derived factor in SHR aortas that facilitates ouabain-induced contractions.
KV 1.3 channels are novel determinants of macrophage-dependent endothelial dysfunction in angiotensin II-induced hypertension in mice
(2021-04) Olivencia, Miguel A.; Martínez Casales, Marta; Peraza, Diego A.; García Redondo, Ana B.; Mondéjar Parreño, Gema; Hernanz, Raquel; Salaices, Mercedes; Cogolludo, Ángel; Pennington, Michael W; Valenzuela, Carmen; Briones, Ana M.
Background and purpose: KV 1.3 channels are expressed in vascular smooth muscle cells (VSMCs), where they contribute to proliferation rather than contraction and participate in vascular remodelling. KV 1.3 channels are also expressed in macrophages, where they assemble with KV 1.5 channels (KV 1.3/KV 1.5), whose activation generates a KV current. In macrophages, the KV 1.3/KV 1.5 ratio is increased by classical activation (M1). Whether these channels are involved in angiotensin II (AngII)-induced vascular remodelling, and whether they can modulate the macrophage phenotype in hypertension, remains unknown. We characterized the role of KV 1.3 channels in vascular damage in hypertension. Experimental approach: We used AngII-infused mice treated with two selective KV 1.3 channel inhibitors (HsTX[R14A] and [EWSS]ShK). Vascular function and structure were measured using wire and pressure myography, respectively. VSMC and macrophage electrophysiology were studied using the patch-clamp technique; gene expression was analysed using RT-PCR. Key results: AngII increased KV 1.3 channel expression in mice aorta and peritoneal macrophages which was abolished by HsTX[R14A] treatment. KV 1.3 inhibition did not prevent hypertension, vascular remodelling, or stiffness but corrected AngII-induced macrophage infiltration and endothelial dysfunction in the small mesenteric arteries and/or aorta, via a mechanism independent of electrophysiological changes in VSMCs. AngII modified the electrophysiological properties of peritoneal macrophages, indicating an M1-like activated state, with enhanced expression of proinflammatory cytokines that induced endothelial dysfunction. These effects were prevented by KV 1.3 blockade. Conclusions and implications: We unravelled a new role for KV 1.3 channels in the macrophage-dependent endothelial dysfunction induced by AngII in mice which might be due to modulation of macrophage phenotype.
Myeloid GRK2 Regulates Obesity-Induced Endothelial Dysfunction by Modulating Inflammatory Responses in Perivascular Adipose Tissue
(MDPI, 2020-10-04) González-Amor, María; Vila-Bedmar, Rocio; Rodrigues-Díez, Raquel; Moreno-Carriles, Rosa; C. Arcones, Alba; Cruces-Sande, Marta; Salaices, Mercedes; Mayor Jr, Federico; Briones, Ana M.; Murga, Cristina
Perivascular adipose tissue (PVAT) is increasingly being regarded as an important endocrine organ that directly impacts vessel function, structure, and contractility in obesity-associated diseases. We uncover here a role for myeloid G protein-coupled receptor kinase 2 (GRK2) in the modulation of PVAT-dependent vasodilation responses.
Pioglitazone reduces angiotensin II-induced COX-2 expression through inhibition of ROS production and ET-1 transcription in vascular cells from spontaneously hypertensive rats
(American Physiological Society, 2014-01-01) Pérez-Girón, José V; Palacios-Ramírez, R; Martín, Ángela; Hernanz, Raquel; Aguado, Andrea; Martínez-Revelles, Sonia; Barrús, María T; Salaices, Mercedes; Alonso, María J
Glitazones have anti-inﬂamma-tory properties by interfering with the transcription of proinﬂamma-tory genes, such as cyclooxygenase (COX)-2, and with ROS produc-tion, which are increased in hypertension. This study analyzedwhether pioglitazone modulates COX-2 expression in hypertension byinterfering with ROS and endothelin (ET)-1. In vivo, pioglitazone (2.5mg·kg 1 ·day 1 , 28 days) reduced the greater levels of COX-2,pre-pro-ET-1, and NADPH oxidase (NOX) expression and activity aswell as O2· production found in aortas from spontaneously hyper-tensive rats (SHRs). ANG II increased COX-2 and pre-pro-ET-1levels more in cultured vascular smooth muscle cells from hyperten-sive rats compared with normotensive rats. The ETA receptor antag-onist BQ-123 reduced ANG II-induced COX-2 expression in SHRcells. ANG II also increased NOX-1 expression, NOX activity, andsuperoxide production in SHR cells; the selective NOX-1 inhibitorML-171 and catalase reduced ANG II-induced COX-2 and ET-1transcription. ANG II also increased c-Jun transcription and phospho-JNK1/2, phospho-c-Jun, and p65 NF- B subunit nuclear proteinexpression. SP-600125 and lactacystin, JNK and NF- B inhibitors,respectively, reduced ANG II-induced ET-1, COX-2, and NOX-1levels and NOX activity. Pioglitazone reduced the effects of ANG IIon NOX activity, NOX-1, pre-pro-ET-1, COX-2, and c-Jun mRNAlevels, JNK activation, and nuclear phospho-c-Jun and p65 expres-sion. In conclusion, ROS production and ET-1 are involved in ANGII-induced COX-2 expression in SHRs, explaining the greater COX-2expression observed in this strain. Furthermore, pioglitazone inhibitsANG II-induced COX-2 expression likely by interfering with NF- Band activator protein-1 proinﬂammatory pathways and downregulat-ing ROS production and ET-1 transcription, thus contributing to theanti-inﬂammatory properties of glitazones.