La inhibición de Rho kinasa disminuye la presión arterial y activa la vía vasodilatadora del sistema renina angiotensina en la pared arterial de ratas hipertensas / Inhibition of Rho-kynase decreases systolic blood pressure and activates the vasodilating pathway

Antecedentes: La activación de Rho kinasa disminuye la formación de óxido nítrico al inhibir eNOS. Por otro lado, el rol de la vía de señalización RhoA/Rho kinasa en la actividad y expresión génica de la enzima clave en la vía vasodilatadora del sistema renina angiotensina (SRA), denominada ECA2, no es conocido. Objetivo: Determinar la participación de la vía RhoA/Rho kinasa en la actividad enzimática y en la expresión de ECA2 y de eNOS en la pared arterial en ratas hipertensas (DOCA-sal). Métodos: Se usaron ratas Sprague Dawley de 150 grs. unifrectomizadas tratadas con desoxicorticosterona (DOCA, 100 mg/Kg/sem sbc) durante 6 semanas. Como controles se usaron ratas unifrectomizadas. Un tercer grupo recibió DOCA y además el inhibidor específico de Rho, fasudil (100 mg/kg/día) por gavage durante 21 días. Al finalizar los tratamientos se determinó la presión arterial sistólica (PAS), la masa relativa del ventrículo izquierdo (MRVI mg*100/g), las actividades de ECA y ECA2 por fluorimetría y la expresión de genes de ECA, ECA2 y eNOS por RT-PCR en la aorta. Conclusión: La mayor expresión de ECA2 inducida por fasudil indujo un aumento significativo de la expresióngénica de eNOS en la pared arterial, lo que pudiera explicar el efecto de fasudil sobre ECA2. La inhibición de Rhokinasa activa la vía vasodilatadora del SRA en la pared arterial de ratas hipertensas aumentando los niveles de ECA2 y de eNOS, y disminuye los niveles de ECA.

Background: Through nitric oxide synthase (eNOS) inhibition, Rho-kynase decreases the formation of NO. The role of the RhoA/Rho kynase signaling pathway upon the activity and gene expression of the enzyme responsible for the vasodilating effects of the renin-angiotensin system (RAS), named ACE2 , is unknown. Aim: To determine the role of the RhoA/Rho kynase pathway on the activity and expression of ACE2 and eNOS in the arterial wall of rats with DOCA-salt induced hypertension. Methods: Sprague Dawley uninephrectomized DOCA hypertensive rats ( DOCA, 100mg/Kg/week sbc during 6 weeks) were used as controls. A third group received the specific Rho inhibitor fasudil (100 mg/Kg/day) in addition to DOCA for 21 days. At the end of the treatment period, blood pressure, relative left ventricular mass (RLVIM,mg*100/g), ACE and ACE2 activities (fluorometry) were determined. The expression of ACE and ACE2 genes, along with eNOS in the aortic wall were determined by RT-PCR. Results: Are expressed as mean +/- SEM.

TLR2 mRNA upregulation in ischemic lobes in mouse partial hepatic ischemia/reperfusion injury model / 华中科技大学学报（医学）（英德文版）

To investigate TLR2 (Toll-like receptor 2) mRNA expression in ischemic hepatic lobes under the condition of partial hepatic ischemia/reperfusion injury in BALB/c mice and its relationship with liver function impairment. A partial ischemia/reperfusion injury model was established. The portal vein and hepatic artery supply to the median and left lobes of the liver were obstructed by an atraumatic artery micro-clip, with the obstruction lasting for about 60 min. Then reperfusion was fulfilled by removal of the clip. The liver samples were collected at the 4th h after the restoration of blood inflow. Total RNA was extracted from the liver samples and analyzed quantitatively by method of real-time PCR. At the same time, portal vein serum and plasma were taken respectively for further detection of the level of endotoxin, tumor necrosis factor alpha (TNF-alpha) and plasmic alanine aminotransferase (pALT). The results indicated that TLR2 mRNA in ischemic lobe was up-regulated markedly in mice partial liver ischemia/reperfusion injury model compared to that in sham operation group (deltaCt: 1.05 +/- 1.02 vs 5.08 +/- 1.36, P<0.001). The level of portal vein pALT and TNF-alpha increased significantly (112.32 +/- 17.56 pg/ml vs 6.07 +/- 5.33 pg/ml, P<0.01; 890 +/- 127 microm/L vs 30 +/- 5 microm/L, P<0.001) . However, the level of portal vein endotoxin remained below the normal line, suggesting a state of non-endotoxemia. TLR2 mRNA expression in ischemic lobe, as well as portal vein pALT and TNF-alpha, was up-regulated in the model of mice partial ischemia/reperfusion injury, suggesting the involvement of TLR2 in ischemia/reperfusion pathological process.

Post-Transcription Regulation of mRNA and Hormone Synthesis and Release at the Anterior Pituitary Gland: Information derived from the recovery of pituitary gonadotrope cell function after with a GnRH agonist

This review presents a summary of post-transcription regulation of mRNAs with a focus on the anterior pituitary gland. The control of gene transcription and production of mRNAs is the predominant form of regulation of hormone synthesis. However, post-transcription regulation of mRNAs provides another level of control of hormone synthesis. Examples of how hormone synthesis can be controlled at the level of mRNA include mRNA nuclear export and subcellular localization, mRNA stability and turnover, and regulation of mRNA translation. The gonadotrope cells of the anterior pituitary have multiple internal effector systems and provide an ideal model cell to study post-transcription regulation of mRNAs. Gonadotrope cells are stimulated to release LH and FSH by hypothalamic GnRH that binds to GnRH receptors. GnRH receptors are coupled to G-proteins and second messenger signaling pathways that involve cAMP and IP3. These signaling pathways are associated with the release of LH and FSH and transcription of mRNAs for LH and FSH. The stability of these mRNAs can be influenced by androgens, estrogens and progestagens. Therapy with a GnRH agonist leads to desensitization of gonadotrope cells to GnRH and a depletion of cellular stores of LH and FSH mRNAs, and content of LH and FSH. After discontinuation of therapy with GnRH agonist, levels of LH and FSH mRNAs return to normal some time before LH and FSH content and secretion are restored. This is indicative of post-transcription regulation of LH and FSH mRNAs. Future studies on post-transcription regulation of mRHAs will provide new molecular insights into how gonadotrope cells balance and integrate stimulation by GnRH with feedback modulation by the gonads.

Antisense mRNA for NPY-Y1 receptor in the medial preoptic area increases prolactin secretion

We investigated the participation of neuropeptide Y-Y1 receptors within the medial preoptic area in luteinizing hormone, follicle-stimulating hormone and prolactin release. Four bilateral microinjections of sense (control) or antisense 18-base oligonucleotides of messenger ribonucleic acid (mRNA) (250 ng) corresponding to the NH2-terminus of the neuropeptide Y1 receptor were performed at 12-h intervals for two days into the medial preoptic area of ovariectomized Wistar rats (N = 16), weighing 180 to 200 g, treated with estrogen (50 µg) and progesterone (25 mg) two days before the experiments between 8.00 and 10:00 a.m. Blockade of Y1 receptor synthesis in the medial preoptic area by the antisense mRNA did not change plasma luteinizing hormone or follicle-stimulating hormone but did increase prolactin from 19.6 + or - 5.9 ng/ml in the sense group to 52.9 + or - 9.6 ng/ml in the antisense group. The plasma hormones were measured by radioimmunoassay and the values are reported as mean + or - SEM. These data suggest that endogenous neuropeptide Y in the medial preoptic area has an inhibitory action on prolactin secretion through Y1 receptors

Importância do fator de crescimento epidérmico (EGF) e seu receptor (EGF-R) no tecido endometrial / Epidermal growth factor (EGF) and its receptor (EGF-R) importance in the endometrial tissue

Os autores fazem uma revisäo sobre a influência que o EGF e seu receptor (EGF-R) exercem no tecido endometrial, enfocando sua possível regulaçäo pelos esteróides e seus receptores e sua importância nos processos de transformaçäo secretora e de decidualizaçäo.