RESUMEN
OBJECTIVE: The current study considers changes of the postnatal brainstem cell number and angiotensin receptors by maternal protein restriction (LP) and LP taurine supplementation (LPT), and its impact on arterial hypertension development in adult life. METHODS AND RESULTS: The brain tissue studies were performed by immunoblotting, immunohistochemistry, and isotropic fractionator analysis. The current study shows that elevated blood pressure associated with decreased fractional urinary sodium excretion (FENa) in adult LP offspring was reverted by diet taurine supplementation. Also, that 12-day-old LP pups present a reduction of 21% of brainstem neuron counts, and, immunohistochemistry demonstrates a decreased expression of type 1 angiotensin II receptors (AT1R) in the entire medial solitary tract nuclei (nTS) of 16-week-old LP rats compared to age-matched NP and LPT offspring. Conversely, the immunostained type 2 AngII (AT2R) receptors in 16-week-old LP nTS were unchanged. CONCLUSION: The present investigation shows a decreased FENa that occurs despite unchanged creatinine clearance. It is plausible to hypothesize an association of decreased postnatal nTS cell number, AT1R/AT2R ratio and FENa with the higher blood pressure levels found in taurine-deficient progeny (LP) compared with age-matched NP and LPT offspring.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Dieta con Restricción de Proteínas , Riñón/metabolismo , Receptores de Angiotensina/biosíntesis , Sodio/orina , Núcleo Solitario/citología , Taurina/farmacología , Animales , Recuento de Células , Creatinina/sangre , Femenino , Litio/metabolismo , Masculino , Bulbo Raquídeo/citología , Bulbo Raquídeo/efectos de los fármacos , Potasio/orina , Embarazo , Ratas , Núcleo Solitario/efectos de los fármacos , Urodinámica/efectos de los fármacosRESUMEN
Renin-Angiotensin System (RAS) plays an important role in the development of Metabolic Syndrome (MS) and in aging. Angiotensin 1-7 (Ang 1-7) has opposite effects to Ang II. All of the components of RAS are expressed locally in adipose tissue and there is over-activation of adipose RAS in obesity and hypertension. We determined serum and abdominal adipose tissue Ang II and Ang 1-7 in control and MS rats during aging and the expression of AT1, AT2 and Mas in white adipose tissue. MS was induced by sucrose ingestion during 6, 12 and 18 months. During aging, an increase in body weight, abdominal fat and dyslipidemia were found but increases in aging MS rats were higher. Control and MS concentrations of serum Ang II from 6-month old rats were similar. Aging did not modify Ang II seric concentration in control rats but decreased it in MS rats. Ang II levels increased in WAT from both groups of rats. Serum and adipose tissue Ang 1-7 increased during aging in MS rats. Western blot analysis revealed that AT1 expression increased in the control group during aging while AT2 and Mas remained unchanged. In MS rats, AT1 and AT2 expression decreased significantly in aged rats. The high concentration of Ang 1-7 and adiponectin in old MS rats might be associated to an increased expression of PPAR-γ. PPAR-γ was increased in adipose tissue from MS rats. It decreased with aging in control rats and showed no changes during aging in MS rats. Ang 1-7/Mas axis was the predominant pathway in WAT from old MS animals and could represent a potential target for therapeutical strategies in the treatment of MS during aging.
Asunto(s)
Angiotensina II/metabolismo , Angiotensina I/metabolismo , Síndrome Metabólico/genética , Fragmentos de Péptidos/metabolismo , Proteínas Proto-Oncogénicas/biosíntesis , Receptor de Angiotensina Tipo 2/biosíntesis , Receptores de Angiotensina/biosíntesis , Receptores Acoplados a Proteínas G/biosíntesis , Tejido Adiposo Blanco/metabolismo , Envejecimiento/genética , Envejecimiento/metabolismo , Envejecimiento/patología , Animales , Regulación de la Expresión Génica , Humanos , Hipertensión/genética , Hipertensión/patología , Síndrome Metabólico/metabolismo , Síndrome Metabólico/patología , Proto-Oncogenes Mas , Ratas , Sistema Renina-Angiotensina/genéticaRESUMEN
Sepsis causes impaired vascular reactivity, hypotension and acute renal failure. The ability of the Escherichia coli endotoxin (lipopolysaccharide [LPS]) to impair agonist-induced contractility in mesangial cells, which contributes to LPS-induced renal dysfunction, was evaluated. Agonist-induced intracellular calcium ([Ca(2+)]i) mobilization was analyzed using angiotensin II (AngII). The effect of LPS on the levels of the renin-angiotensin system (RAS) components and the roles of vasodilatation-inducing molecules including AT2 receptor (AT2R) and nitric oxide (NO) in the cell reactivity were also evaluated. Confluent human mesangial cells (HMCs) were stimulated with LPS (0111-B4, 100 microg/mL). AngII-induced [Ca(2+)]i mobilization was measured by fluorometric analysis using Fura-2AM in the absence and presence of an AT2R antagonist (PD123319). The mRNA and protein levels for angiotensinogen, renin, angiotensin-converting enzyme, AT1R and AT2R were analyzed by realtime reverse transcriptase-polymerase chain reaction and Western blot, respectively. NO production was measured by the chemiluminescence method in the culture media after 24, 48 and 72 h of LPS incubation. After 24 h, LPS-stimulated HMCs displayed lower basal [Ca(2+)]i and an impaired response to AngII-induced rise in [Ca(2+)]i. LPS significantly increased AT2R levels, but did not cause significant alterations of RAS components. PD123319 restored both basal and AngII-induced [Ca(2+)]i peak, suggesting an involvement of AT2R in these responses. The expected increase in NO production was significant only after 72 h of LPS incubation and it was unaffected by PD123319. Results showed that LPS reduced the reactivity of HMCs to AngII and suggest that the vasodilatation induced by AT2R is a potential mediator of this response through a pathway independent of NO.
Asunto(s)
Señalización del Calcio/efectos de los fármacos , Escherichia coli/patogenicidad , Lipopolisacáridos/toxicidad , Células Mesangiales/efectos de los fármacos , Receptores de Angiotensina/efectos de los fármacos , Angiotensina II/metabolismo , Angiotensinógeno/biosíntesis , Western Blotting , Perfilación de la Expresión Génica , Humanos , Óxido Nítrico/metabolismo , Peptidil-Dipeptidasa A/biosíntesis , Receptores de Angiotensina/biosíntesis , Renina/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Neonatal handling affects the hypothalamus-pituitary-gonadal axis in female rats. Indeed, postnatal handling induces anovulatory estrous cycles and decreases sexual receptiveness. On the other hand, Angiotensin II (Ang II) infused into the medial amygdala (MeA) reduces sexual behavior in male and female rats. Considering this, and that gonadal steroid secretion after copulatory behavior is important for reproductive success, the purpose of the present study was to investigate whether the reduction in sexual receptiveness in neonatally handled female rats is mediated by changes in Ang II receptor density in MeA. Moreover, gonadal steroid secretion after sexual behavior was analyzed. Two groups of female Wistar rats were studied: nonhandled (pups were left undisturbed) and handled (pups were handled for 1 min once a day during the first 10 days of life). Once they were 80-85 days old in the evening of the proestrus day, sexual receptiveness was recorded and after that the animals were killed by decapitation. Trunk blood samples were collected, and plasma estradiol and progesterone were measured by radioimmunoassay. The brains were removed for Ang II receptor autoradiography in MeA. The decreased lordosis quotient in the neonatally handled group was confirmed in the present study. Neonatal handling also reduced the progesterone concentration in the plasma, but did not change the estradiol and the density of Ang II receptors in MeA. The reduced progesterone could be due to the decreased lordosis frequency of handled females. However, this decreased sexual receptiveness is not mediated by changes in Ang II receptors in MeA.
Asunto(s)
Amígdala del Cerebelo/metabolismo , Estro/fisiología , Manejo Psicológico , Progesterona/metabolismo , Receptores de Angiotensina/biosíntesis , Conducta Sexual Animal/fisiología , Animales , Animales Recién Nacidos , Autorradiografía , Femenino , Masculino , Progesterona/sangre , Ratas , Ratas WistarRESUMEN
The role of angiotensin II (AngII) in ovarian steroidogenesis is not clearly understood. In order to study its action on progesterone synthesis and to determine which receptor subtype is involve, granulosa cells obtained from women undergoing in-vitro fertilization were cultured for 2 or 4 days and then incubated in the presence of AngII (10(-7) M) with or without human chorionic gonadotrophin (HCG, 10 IU/ml) for 3 or 18 h. In cells cultured for 2 days, incubation with AngII decreased progesterone secretion by 36%, and inhibited activity of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) by 87% (P < 0.05), although its expression was not significantly reduced. However, in cells cultured for 4 days, progesterone production was enhanced by incubation with AngII (38%), and no change was observed in 3 beta-HSD expression. Both inhibitory and stimulatory effects were dose-dependent. Progesterone secretion was increased (93%) by incubation with HCG of cells cultured for 4, but not for 2 days, and no potentiation was observed with AngII. Treatment with PD123177 completely blocked the action of AngII and decreased the HCG-stimulated secretion of progesterone by 27%. Angiotensin type-2 (AT2) receptor mRNA was expressed in cells cultured for 4 days. In conclusion, AngII showed a regulatory role in in-vitro progesterone production by human granulosa luteinized cells, modulating the activity of 3 beta-HSD. It is likely that these actions may be mediated via membrane receptors, possibly of the AT2 receptor family.
Asunto(s)
Angiotensina II/farmacología , Células de la Granulosa/metabolismo , Progesterona Reductasa/metabolismo , Progesterona/biosíntesis , Receptores de Angiotensina/biosíntesis , Células Cultivadas , Gonadotropina Coriónica/farmacología , Femenino , Células de la Granulosa/citología , Células de la Granulosa/efectos de los fármacos , Humanos , Cinética , Complejos Multienzimáticos , ARN Mensajero/biosíntesis , Receptor de Angiotensina Tipo 2 , Esteroide Isomerasas , Factores de Tiempo , Transcripción Genética/efectos de los fármacosRESUMEN
Angiotensin II receptors of the AT1 subtype were very highly expressed in medroxyprogesterone-induced ductal adenocarcinomas of the mammary gland in BALB/c mice. AT1 receptors are associated only to neoplastic epithelial cells. Lobular adenocarcinomas expressed very few AT1 receptors and expressed AT2 receptors only in areas corresponding to peritumoral connective tissue. Binding to angiotensin converting enzyme was present in all adenocarcinomas studied and was higher in ductal than in lobular adenocarcinomas. Normal mammary gland did not express either angiotensin II receptors or angiotensin converting enzyme. The present results are the first demonstration of angiotensin receptor subtypes and converting enzyme in mammary adenocarcinomas differentially expressed in tumors of ductal and lobular origin. Localization of receptor subtypes could be useful to study the differentiation of mammary cells during experimental mammary carcinogenesis in mice.