Regulation of steroidogenesis by atrial natriuretic peptide (ANP) in the rat testis: differential involvement of GC-A and C receptors.

Previous studies have established a stimulatory effect of natriuretic peptides (NP) on testosterone production in mouse Leydig cells as intense as that of LH. Chronic administration of ANP in mice, on the other side, reduced testosterone levels. So, the understanding of the role of ANP on testicular steroidogenesis has been impaired by discrepant findings. The aim of the present study was to clarify the physiological role of ANP in the rat testis steroidogenesis using a model that preserves the interactions between testis cells and a medium devoid of any circulating factors that could interfere with testosterone production. First, ANP was immunolocalized in the interstitial compartment of the rat testis, mainly in Leydig cells. We also determined the presence of ANP and both GC-A (guanylyl cyclase A) and C receptors by real-time PCR in testis. Perfusion in vitro of testis with ANP (1 and 3x10(-7)M) stimulated testosterone production in a time- and dose-dependent manner. On the other side, testosterone secretion induced by LH was blunted by ANP. Similar effect was obtained using the specific C receptor ligand, cANF, indicating the involvement of C receptor in such response. In conclusion, ANP stimulated testosterone production in the rat testis perfused in vitro but decreased testosterone production LH-induced, effect that seems to involve C receptor. To this extent, our results suggest the existence of a local and complex peptidergic system in the rat testis, involving ANP and its receptors that could importantly modulate the androgen biosynthesis.

Maternal flaxseed oil intake during lactation changes body fat, inflammatory markers and glucose homeostasis in the adult progeny: role of gender dimorphism.

We evaluated maternal flaxseed oil intake during lactation on body composition, lipid profile, glucose homeostasis and adipose tissue inflammation in male and female progeny at adulthood. Lactating rats were divided into the following: control 7% soybean oil (C), hyper 19% soybean oil (HS) and hyper 17% flaxseed oil+2% soybean oil (HF). Weaned pups received a standard diet. Offspring were killed in PN180. Male HF presented higher visceral adipose tissue (VAT) and triacylglycerol, and female HF showed insulin resistance. Both male and female HF had hyperleptinemia, and only male HF had hyperprolactinemia. In VAT, male HF presented lower PPAR-γ expressions and higher TNF-α, IL-6, IL-1ß and IL-10 expressions; in subcutaneous adipose tissue (SAT), they presented lower PPAR-γ and TNF-α expressions. Female HF presented higher leptin, as well as lower adiponectin, TNF-α, IL-6 and IL-1ß expressions in VAT and lower TNF-α in SAT. Flaxseed oil during lactation leads to gender-specific effects with more adiposity and dyslipidemia in male and insulin resistance in female. Higher prolactin and inflammatory cytokines in male could play a role in these gender differences. We suggest that the use of flaxseed oil during lactation increases metabolic syndrome risk in the adult progeny.

Nandrolone decanoate induces cardiac and renal remodeling in female rats, without modification in physiological parameters: The role of ANP system.

UNLABELLED: Anabolic-androgenic steroids are misused, including women, but little is known about the cardiovascular effects of these drugs on females. AIM: Evaluated the effects of nandrolone decanoate (ND), physical exercise and estrogen deficiency on female rats. MAIN METHODS: Female Wistar rats were divided into 8 groups: S and OVX: (SHAM: sham surgery; OVX: ovariectomy, vehicle), SE and OVXE (resistance exercise 5 times a week, vehicle), SD and OVXD (treated with ND, 20 mg/kg/week for 4 weeks); SDE and OVXDE. Treatments were initiated 21 days after surgery. The Bezold­Jarisch reflex was assessed by Phenylbiguanide administration. The right atrium, kidney, and serum were collected for molecular analyses by RT-PCR of atrial natriuretic peptide (ANP), A-type natriuretic peptide receptor (NPR-A) and NPR-C. ELISA assay to estradiol and testosterone concentrations. The gastrocnemius muscle, heart and kidney weights/tibia length were measured.Morphometric analysis of heart was made (H/E) and collagen content of heart and kidney were evaluated using Pirossirius Red. KEY FINDINGS: ND treatment increased ANP expression on atrium and decreased NPR-A expression in kidney. Physical exercise and ovariectomy did not alter this parameter. NPR-C level was reduced in the SDE and OVXDE. Renal and cardiac hypertrophy was observed after ND treatment, with collagen deposition. Plasma estrogen concentrations were reduced and serum testosterone concentrations were increased after ND treatment. SIGNIFICANCE: ANP has an important role in modulating the cardiovascular effects of ND in females. Thismodulating may have occurred by the increasing ANP expression, reducing NPR-A and NPR-C expression levels, and changing sex hormone levels.

Estrogen therapy attenuates adiposity markers in spontaneously hypertensive rats.

Ovarian hormones modulate the metabolism of adipose cells and present a protective effect against hypertension. The aim of this study was to compare the effect of estradiol on adiposity markers in spontaneously hypertensive rats. Ovariectomized spontaneously hypertensive rats treated with estradiol (5 µg/100 g/day), three weeks after ovariectomy, presented decreased blood pressure and insulin levels and increased hepatic glycogen content. Periuterine or mesenteric adipocytes from treated animals were smaller as compared to vehicle treated group, whereas no differences were observed in relation to the number of cells. Basal rates of glycerol release were higher only in periuterine adipocytes of treated rats. The increment of glycerol release over basal values in response to isoproterenol was 400% and 440%, 283% and 330% for vehicle and estradiol treated periuterine and mesenteric adipocytes, respectively. The estradiol treated group was more sensitive to insulin inhibition of isoproterenol-stimulated lipolysis than the control animals. The lipoprotein lipase activity decreased after treatment, only in periuterine adipose tissue. Estradiol administration increased basal and insulin-stimulated rates of glucose transport in adipocytes of both sites, although the values obtained by periuterine were higher than those observed for mesenteric adipocytes. Both adipose tissues from treated animals exhibited a decreased expression of the peroxisome proliferator-activated receptor-γ, but an increased expression of peroxisome proliferator-activated receptor-α in liver. These findings suggest that estrogen administration attenuates adiposity markers of spontaneously hypertensive rats as a result of the decreased expression levels of peroxisome proliferator-activated receptor-γ in adipose tissue and increased expression of peroxisome proliferator-activated receptor-α in liver.

Natriuretic peptide system: a link between fat mass and cardiac hypertrophy and hypertension in fat-fed female rats.

The present study was designed to develop an animal model of hypertension and cardiac hypertrophy associated with obesity in female rats. Furthermore, we studied the involvement of the natriuretic peptide system in the mechanisms of these conditions. Obesity was induced in Wistar rats by a high fat diet and ovariectomy. The rats were divided into four groups: ovariectomized or sham-operated with high-fat diet and ovariectomized or sham-operated with control diet. After 24 weeks of diet, rats were killed, and their tissues were removed. Cardiac atrial natriuretic peptide (ANP), clearance receptor (NPr-C) gene expression was determined by PCR. ANP concentrations were measured in plasma. Ovariectomized fat-fed rats (OF) showed increased body weight, visceral fat depot and blood pressure and decreased sodium excretion compared to other groups. Also, these rats showed higher heart-to-body weight and cell diameters of ventricular cardiomyocytes and lower cardiac ANP mRNA and plasma ANP than the control group. The adipocyte and renal NPr-C mRNA of OF rats were higher than the control group. These data showed that combined ovariectomy and high fat diet elicited obesity, hypertension and cardiac hypertrophy. These results suggest that the impairment of the natriuretic peptide system may be one of the mechanisms involved not only in development of hypertension but also in cardiac hypertrophy associated with obesity in ovariectomized rats.

Pressão arterial e concentração plasmática do peptídeo atrial natriurético e do peptídeo natriurético tipo B, em gestações complicadas pela pré-eclâmpsia / Influence of atrial natriuretic peptide and type B natriuretic peptide plasma levels on arterial pressure in pregnancies complicated by preeclampsia

OBJETIVO: o estudo busca determinar a existência de associação entre a elevação da pressão arterial e os níveis plasmáticos dos peptídeos natriuréticos ANP e BNP, na gestaçäo complicada pela pré-eclâmpsia. MÉTODOS: em estudo transversal caso-controle, pareado por idade gestacional, 25 grávidas normotensas e 61 portadoras de pré-eclâmpsia foram avaliadas quanto ao nível da pressão arterial e às concentraçöes plasmáticas dos peptídeos natriuréticos ANP e BNP. Exames clínico e laboratoriais foram realizados para o diagnóstico de pré-eclâmpsia, sendo a pressäo arterial medida de forma näo invasiva. As dosagens hormonais foram obtidas por radioimunoensaio, após extraçäo em colunas Sep-pak C18. Os valores médios das concentraçöes plasmáticas do ANP e BNP foram comparados entre grupos com pressäo arterial progressivamente maiores. A correlaçäo entre os valores da pressäo arterial e os níveis plasmáticos do ANP e BNP no sangue materno foi também investigada pela de análise de regressäo no grupo completo de gestantes e em grupos específicos excluindo-se a hipertensäo anterior à gestaçäo e, em seguida, excluindo-se aquelas sem hipertensäo prévia. RESULTADOS: os valores plasmáticos de ANP foram 41.5±7.3, 78.4±13.1 e 89.2±13.4 pg/mL (p<0,00001) e os de BNP plasmático foram 79.5±15.8, 176.7±42.2 e 208.3±63.5 pg/mL (p=0,005), respectivamente, para os grupos de pressäo arterial média =107 mmHg, 107-139 mmHg e =140 mmHg. Verificou-se correlaçäo positiva entre as concentrações plasmáticas do ANP e os níveis pressóricos na pré-eclâmpsia, independente da existência de estado hipertensivo prévio à gestaçäo (p<0,0001 para pré-eclâmpsia e p<0,01 para pré-eclampsia sobreposta à hipertensäo arterial crônica), ao passo que as dosagens de BNP näo se mostraram associadas à pressão arterial no grupo com hipertensäo arterial prévia à gestação (p=0,004 para pré-eclâmpsia e p=0,18 para pré-eclampsia sobreposta à hipertensäo arterial crônica). CONCLUSÃO: o agravamento da hipertensäo na pré-eclâmpsia correlacionou-se com as concentraçöes séricas do ANP e BNP, embora os valores do BNP possam ser influenciados pela existência de estado hipertensivo prévio

Etiopatogenia do diabete melito gestacional / Etiopathogeny of gestational diabetes mellitus

Os fatores que concorrem para o chamado efeito metabólico diabetogênico da gravidez incluem modificaçöes da secreçäo hormonal e da açäo periférica dos hormônios no organismo materno, bem como a síntese e liberaçäo dos hormônios placentários. Ainda näo está claro se o diabete gestacional é causadopor uma secreçäo inadequada de insulina em resposta à ingestäo de carboidratos, por um aumento de resistência periférica à açäo da insulina, ou por ambos os fatores.