Female Hormones in Renal Physiology: Salt Sensitivity and Regulation of Epithelial Proliferation

Un tercio de la población mundial tiene niveles anormalmente altos de presión arterial, hipertensión, responsable de casi el 50% de las muertes por accidente cerebrovascular y enfermedad coronaria. La sensibilidad a la sal es un factor de riesgo para la morbilidad y mortalidad cardiovascular y también para otras enfermedades. En estudios previos describimos un modelo de hipertensión sal sensible (HSS) en ratas Wistar ovariectomizadas (oVx) adultas. Las ratas oVx son normotensas con ingesta normal de sal (NS, 0.24% de NaCl), pero desarrollan un perfil de HSS con una ingesta elevada de sal (HS, 1% de NaCl). En los estudios en riñón encontramos que el circuito receptor D1 de dopamina, citocromo P450 4A y Na+, K+-ATPasa está alterado por la ausencia de hormonas ováricas, lo que se asocia a menor excreción de sodio e hipertensión arterial. La ingesta HS en ratas oVx también promueve cambios en la expresión de proteínas relacionadas con el transporte de sodio en células mononucleares de sangre periférica, principalmente linfocitos periféricos. Por lo tanto, el transporte de sodio se modifica en varios niveles de la fisiología normal. En estudios recientes observamos que el estradiol aumenta la proliferación y diferenciación de células epiteliales en cultivos de corteza renal humana. Sensibilidad a la sal, inmunidad adaptativa, presión arterial y proliferación de células epiteliales en riñón son fenómenos de gran importancia biológica regulados por estradiol.Female sex hormones participate in the regulation of blood pressure and renal epithelial proliferation, effects not related to their reproductive function. About one-third of the world’s population has abnormally high levels of blood pressure, hypertension, which is responsible for almost 50% of deaths from stroke and coronary heart disease. Salt sensitivity is a risk factor for cardiovascular morbidity and mortality and other diseases as well. We reported a model of salt sensitive hypertension in adult ovariectomized (oVx) Wistar rats. oVx rats are normotensive under normal salt intake (NS, 0.24% NaCl), but upon a high salt intake (HS, 1% NaCl) oVx rats developed a blood pressure profile of salt-sensitive hypertension. Our studies on kidney molecules related to sodium balance found that the circuit dopamine D1-like receptor, cytochrome P450 4A and Na+, K+-ATPase is altered by the absence of ovary hormones which is accompanied by a reduced ability to excrete sodium. In oVx rats HS intake also promotes changes in the expression of proteins related to sodium transport in peripheral blood mononuclear cells, mainly peripheral lymphocytes. Therefore, sodium transport is modified at several levels of normal physiology. Lately, we described that estradiol increases the rate of renal epithelial cell proliferation in primary cultures developed from human renal cortex. Thus, salt sensitivity, adaptive immunity, blood pressure and renal cell proliferation are complex biological responses regulated by female sex hormones.Fil: Vlachovsky, Sandra Gabriela. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Sanchez, Daiana Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Di Ciano, Luis Alberto. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Oddo, Elisabet Mónica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Azurmendi, Pablo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Silberstein, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Ibarra, Fernando R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Concerted regulation of renal plasma flow and glomerular filtration rate by renal dopamine and NOS I in rats on high salt intake

Under high sodium intake renal dopamine (DA) increases while NOS I expression in macula densa cells (MD) decreases. To explore whether renal DA and NOS I, linked to natriuresis and to the stability of the tubuloglomerular feedback, respectively, act in concert to regulate renal plasma flow (RPF) and glomerular filtration rate (GFR). Male Wistar rats were studied under a normal sodium intake (NS, NaCl 0.24%) or a high sodium intake (HS, NaCl 1% in drinking water) during the 5 days of the study. For the last two days, the specific D1-like receptor antagonist SCH 23390 (1 mg kg bwt−1 day−1, sc) or a vehicle was administered. HS intake increased natriuresis, diuresis, and urinary DA while it decreased cortical NOS I expression (P < 0.05 vs. NS), Nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity in MD (P < 0.001 vs. NS) and cortical nitrates+nitrites (NOx) production (NS 2.04 ± 0.22 vs. HS 1.28 ± 0.10 nmol mg protein−1, P < 0.01). Treatment with SCH 23390 to rats on HS sharply decreased hydroelectrolyte excretion (P < 0.001 vs. HS) while NOS I expression, NADPH-d activity and NOx production increased (P < 0.05 vs. HS for NOS I and P < 0.001 vs. HS for NADPH-d and NOx). SCH 23390 increased RPF and GFR in HS rats (P < 0.01 HS+SCH vs. HS). It did not cause variations in NS rats. Results indicate that when NS intake is shifted to a prolonged high sodium intake, renal DA through the D1R, and NOS I in MD cells act in concert to regulate RPF and GFR to stabilize the delivery of NaCl to the distal nephron.Fil: Ibarra, Mariano Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Albertoni Borghese, Maria Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Majowicz, Mónica Patricia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Ortiz, María C.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Loidl, Cesar Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Rey Funes, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Di Ciano, Luis Alberto. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Ibarra, Fernando Raúl. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentin

Behavior of the renal kallikrein in spontaneously hypertensive rats: Influence of sexual hormones and aldosterone-sensitive distal nephron ion channels

The renal kallikrein-kinin system (RKKS) has been related to blood pressure control and sodium and water balance. We have previously shown that female spontaneously hypertensive rats (SHR) have high urinary kallikrein activity (UKa) and lower blood pressure (BP) than males whereas ovariectomy stimulates UKa and diminishes BP. We also showed that high K+ intake and prepuberal gonadectomy (Gx) diminish BP with a concomitant increase in UKa and plasma aldosterone levels. Since kallikrein co-localize in the same distal nephron segments of aldosterone effectors, we explored the effect of pharmacological blockage of aldosterone receptor, epithelial Na+ (ENaC) and the rectifying outer medulla K+ (ROMK) channels in different gonad contexts on the gene expression, renal tissue content and urine release of kallikrein. Klk1 gene expression was determined by real-time PCR and enzymatic activity of kallikrein by the amidolytic method. We found that the inhibition of the aldosterone receptor by spironolactone increases kallikrein renal tissue storage and decreases its urinary activity, especially in Gx rats. Moreover, ENaC blockade by benzamil increases the renal content of kallikrein without affecting synthesis or excretion, especially in females and Gx animals, while the inhibition of ROMK by glibenclamide increases the synthesis and renal content of kallikrein only in intact male animals. We concluded that RKKS regulation showed sexual dimorphism and seemed to be modulated by sex hormones throughout a process involving aldosterone and the aldosterone-sensitive ion channels.Fil: Azurmendi, Pablo Javier. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Toro, Ayelen Rayen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Celía, Alejandro Fabián. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Guevara, Darío. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Solerno, Martín Rogelio. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Di Ciano, Luis Alberto. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Toledo, Jorge Eduardo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Ibarra, Fernando Raúl. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Arrizurieta, Elvira. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Oddo, Elisabet Mónica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Search for central exclusive production of top quark pairs in proton-proton collisions at s\sqrt{s} = 13 TeV with tagged protons

International audienceA search for the central exclusive production of top quark-antiquark pairs ($\mathrm{t\bar{t}}$) is performed for the first time using proton-tagged events in proton-proton collisions at the LHC at a centre-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 29.4 fb$^{-1}$. The $\mathrm{t\bar{t}}$ decay products are reconstructed using the central CMS detector, while forward protons are measured in the CMS-TOTEM precision proton spectrometer. An observed (expected) upper bound on the production cross section of 0.59 (1.14) pb is set at 95% confidence level, for collisions of protons with fractional momentum losses between 2 and 20%

Search for central exclusive production of top quark pairs in proton-proton collisions at s\sqrt{s} = 13 TeV with tagged protons

International audienceA search for the central exclusive production of top quark-antiquark pairs ($\mathrm{t\bar{t}}$) is performed for the first time using proton-tagged events in proton-proton collisions at the LHC at a centre-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 29.4 fb$^{-1}$. The $\mathrm{t\bar{t}}$ decay products are reconstructed using the central CMS detector, while forward protons are measured in the CMS-TOTEM precision proton spectrometer. An observed (expected) upper bound on the production cross section of 0.59 (1.14) pb is set at 95% confidence level, for collisions of protons with fractional momentum losses between 2 and 20%

Search for central exclusive production of top quark pairs in proton-proton collisions at s\sqrt{s} = 13 TeV with tagged protons

International audienceA search for the central exclusive production of top quark-antiquark pairs ($\mathrm{t\bar{t}}$) is performed for the first time using proton-tagged events in proton-proton collisions at the LHC at a centre-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 29.4 fb$^{-1}$. The $\mathrm{t\bar{t}}$ decay products are reconstructed using the central CMS detector, while forward protons are measured in the CMS-TOTEM precision proton spectrometer. An observed (expected) upper bound on the production cross section of 0.59 (1.14) pb is set at 95% confidence level, for collisions of protons with fractional momentum losses between 2 and 20%

Search for central exclusive production of top quark pairs in proton-proton collisions at s= \sqrt{s} = 13 TeV with tagged protons

A search for the central exclusive production of top quark-antiquark pairs ($\mathrm{t} \bar{\mathrm{t}}$) is performed for the first time using proton-tagged events in proton-proton collisions at the LHC at a centre-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 29.4 fb$^{-1}$. The $\mathrm{t} \bar{\mathrm{t}}$ decay products are reconstructed using the central CMS detector, while forward protons are measured in the CMS-TOTEM precision proton spectrometer. An observed (expected) upper bound on the production cross section of 0.59 (1.14) pb is set at 95% confidence level, for collisions of protons with fractional momentum losses between 2 and 20%.A search for the central exclusive production of top quark-antiquark pairs ($\mathrm{t\bar{t}}$) is performed for the first time using proton-tagged events in proton-proton collisions at the LHC at a centre-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 29.4 fb$^{-1}$. The $\mathrm{t\bar{t}}$ decay products are reconstructed using the central CMS detector, while forward protons are measured in the CMS-TOTEM precision proton spectrometer. An observed (expected) upper bound on the production cross section of 0.59 (1.14) pb is set at 95% confidence level, for collisions of protons with fractional momentum losses between 2 and 20%

Search for central exclusive production of top quark pairs in proton-proton collisions at s\sqrt{s} = 13 TeV with tagged protons

International audienceA search for the central exclusive production of top quark-antiquark pairs ($\mathrm{t\bar{t}}$) is performed for the first time using proton-tagged events in proton-proton collisions at the LHC at a centre-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 29.4 fb$^{-1}$. The $\mathrm{t\bar{t}}$ decay products are reconstructed using the central CMS detector, while forward protons are measured in the CMS-TOTEM precision proton spectrometer. An observed (expected) upper bound on the production cross section of 0.59 (1.14) pb is set at 95% confidence level, for collisions of protons with fractional momentum losses between 2 and 20%

Development of the CMS detector for the CERN LHC Run 3

International audienceSince the initial data taking of the CERN LHC, the CMS experiment has undergone substantial upgrades and improvements. This paper discusses the CMS detector as it is configured for the third data-taking period of the CERN LHC, Run 3, which started in 2022. The entire silicon pixel tracking detector was replaced. A new powering system for the superconducting solenoid was installed. The electronics of the hadron calorimeter was upgraded. All the muon electronic systems were upgraded, and new muon detector stations were added, including a gas electron multiplier detector. The precision proton spectrometer was upgraded. The dedicated luminosity detectors and the beam loss monitor were refurbished. Substantial improvements to the trigger, data acquisition, software, and computing systems were also implemented, including a new hybrid CPU/GPU farm for the high-level trigger

Development of the CMS detector for the CERN LHC Run 3

Since the initial data taking of the CERN LHC, the CMS experiment has undergone substantial upgrades and improvements. This paper discusses the CMS detector as it is configured for the third data-taking period of the CERN LHC, Run 3, which started in 2022. The entire silicon pixel tracking detector was replaced. A new powering system for the superconducting solenoid was installed. The electronics of the hadron calorimeter was upgraded. All the muon electronic systems were upgraded, and new muon detector stations were added, including a gas electron multiplier detector. The precision proton spectrometer was upgraded. The dedicated luminosity detectors and the beam loss monitor were refurbished. Substantial improvements to the trigger, data acquisition, software, and computing systems were also implemented, including a new hybrid CPU/GPU farm for the high-level trigger.Since the initial data taking of the CERN LHC, the CMS experiment has undergone substantial upgrades and improvements. This paper discusses the CMS detector as it is configured for the third data-taking period of the CERN LHC, Run 3, which started in 2022. The entire silicon pixel tracking detector was replaced. A new powering system for the superconducting solenoid was installed. The electronics of the hadron calorimeter was upgraded. All the muon electronic systems were upgraded, and new muon detector stations were added, including a gas electron multiplier detector. The precision proton spectrometer was upgraded. The dedicated luminosity detectors and the beam loss monitor were refurbished. Substantial improvements to the trigger, data acquisition, software, and computing systems were also implemented, including a new hybrid CPU/GPU farm for the high-level trigger