A novel inbred rat model with inducible hypertension has been generated using a renin transgene under the transcriptional control of the cytochrome P450, Cyp1a1 promoter. The degree and duration of hypertension are regulated tightly by administration of the natural xenobiotic indole-3 carbinol and can be readily reversed. Induction experiments reveal distinct temporal and mechanistic responses to hypertensive injury in different vascular beds, which is indicative of differential susceptibility of organs to a hypertensive stimulus. The mesentery and heart exhibited the greatest sensitivity to damage, and the kidney showed an adaptive response prior to the development of malignant hypertensive injury. Quantitative analysis of morphological changes induced in mesenteric resistance arteries suggest eutrophic remodeling of the vessels. Kinetic evidence suggests that locally activated plasma prorenin may play a critical role in mediating vascular injury. This model will facilitate studies of the cellular and genetic mechanisms underlying vascular injury and repair and provide a basis for the identification of novel therapeutic targets for vascular disease.Essential hypertension has a complex multifactorial phenotype. Both genetic and environmental factors influence its development, and understanding the pathogenesis of complications such as vascular lesions and end-organ damage may lead to more specific treatment and targeted intervention.We have identified candidate loci in rats that may contribute to target organ damage and mortality in malignant hypertension (MH), 1 a condition characterized by an accelerated rise in blood pressure, endothelial injury, activation of the reninangiotensin system, and microangiopathy (1). Several animal models have been generated to investigate the pathophysiology of hypertensive vascular injury. Most animal models of MH to date require surgical or pharmacological intervention to precipitate onset or depend on the constitutive expression of endogenous genes or heterologous transgenes (2-5). In rats doubly transgenic for human renin and angiotensinogen genes, hypertension and fibrinoid vasculitis (5) accompanied by alteration in surface adhesion molecules, proinflammatory cytokines, fibrogenic mediators and leukocyte infiltration (6) have been reported. In most of these models, the onset of disease cannot be determined precisely.The initiation events of pathological processes can only be studied in an animal model in which hypertension is induced by tightly temporally regulated gene expression. If the onset and level of hypertension can be controlled, then the cellular and molecular events during initiation of the vascular and organ injury can be identified unequivocally. Reversibility of the gene expression provides an opportunity to study the molecular and cellular basis of repair. We therefore have generated inbred transgenic rats with inducible hypertension using the cytochrome P450 promoter, Cyp1a1, to drive expression of the mouse Ren-2 gene. The transgene is expressed primarily ...

The cyp1a1ren-2 transgenic rat model allows for chronic dose-dependent titration of arterial pressure by a simple and non-invasive intervention, making this strain a useful model to study malignant and nonmalignant arterial hypertension. High circulating prorenin levels per se do not cause glomerulosclerosis.

Background/Aims: Cutaneous sun exposure and dietary vitamin D intake are important determinants of vitamin D status. The objective of the present study was to evaluate the vitamin D status of a group of healthy adolescent students living in Brazil. Methods: One hundred and thirty-six adolescents, 64 boys and 72 girls, aged 16–20 years old, living in a rural town in the state of São Paulo, Brazil, participated in this study. Results: The mean dietary vitamin D intake was 140 (120–156) IU/day [3.5 (3.0–3.9) μg/day]. Only 14.9% of the students met the daily adequate intake recommendation of vitamin D. Only 27.9% practice physical activity outdoors and 17.6% of the adolescents apply sunscreen daily. The mean 25(OH)D concentration was 73.0 (22.0) nmol/l [29.2 (8.8) ng/ml]. Vitamin D insufficiency was observed in 60% of adolescents. Conclusions: The present study suggests that even in a sunny climate like Brazil the prevalence of vitamin D insufficiency in adolescents is high. Most likely this is due to low intakes of vitamin D in this group. Due to the limited extent of natural dietary sources of vitamin D, a policy of vitamin D food fortification should be considered in the future, and in the meantime greater use of vitamin D supplements in this population group should be encouraged to provide the increased amounts of this essential nutrient for optimal health.

One important goal in cardiology is to prevent necrotic cell death in the heart. Necrotic cell death attracts neutrophils and monocytes into the injured myocardium. The consequences are fibrosis, remodelling and cardiac failure. The renin-angiotensin system promotes the development of cardiac failure. Recently, alternative renin transcripts have been identified lacking the signal sequence for a cotranslational transport to the endoplasmatic reticulum. These transcripts encode for a cytosolic renin with unknown functions. The expression of this alternative transcript increases after myocardial infarction. We hypothesized that cytosolic renin plays a role in survival and death of cardiomyocytes. To test this hypothesis, we overexpressed secretory or cytosolic renin in H9c2 cardiomyblasts and determined the rate of proliferation, necrosis and apoptosis. Proliferation rate, as indicated by BrdU incorporation into DNA, was reduced by secretory and cytosolic renin (cells transfected with control vector: 0.33 ± 0.06; secretory renin: 0.12 ± 0.02; P < 0.05; cytosolic renin: 0.15 ± 0.03; P < 0.05). Necrosis was increased by secretory renin but decreased by cytosolic renin (LDH release after 10 days from cells transfected with control vector: 68.5 ± 14.9; secretory renin: 100.0 ± 0; cytosolic renin: 25.5 ± 5.3% of content, each P < 0.05). Mitochondrial apoptosis, as indicated by phosphatidylserin translocation to the outer membrane, was unaffected by secretory renin but increased by cytosolic renin (controls: 23.8 ± 3.9%; secretory renin: 22.1 ± 4.7%; cytoplasmatic renin: 41.2 ± 3.8%; P < 0.05). The data demonstrate that a cytosolic renin exists in cardiomyocytes, which in contradiction to secretory renin protects from necrosis but increases apoptosis. Non-secretory cytosolic renin can be considered as a new target for cardiac failure.

SummaryOsteoporosis is a global health problem characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Nutrition plays a critical role in reducing the risk of osteoporosis through its effect on all of these fragility factors, especially on the development and maintenance of bone mass. An adequate calcium, vitamin D and protein intake resulted in reduced bone remodeling, better calcium retention, reduced age-related bone loss, and reduced fracture risk. Recent evidence indicates that a healthy dietary pattern including dairy products (mainly fat free), fruit and vegetables and adequate amounts of meat, fish and poultry is positively related to bone health. Furthermore, mineral and vitamin supplementation should be closely monitored by health professionals since it could have adverse effects and be insufficient to ensure optimal protection of bone health. Arq Bras Endocrinol Metab. 2010;54(2):179-85 Keywords Osteoporosis; bone mass; nutrition intake; calcium; vitamin D; protein SumárioA osteoporose é um problema de saúde global, caracterizada por baixa massa óssea e deterioração da microarquitetura do tecido ósseo, com consequente aumento da fragilidade óssea e suscetibilidade a fraturas. A nutrição desempenha um papel fundamental na redução do risco de osteoporose por seu efeito sobre todos os fatores relacionados à fragilidade óssea, principalmente no desenvolvimento e na manutenção da massa óssea. Uma adequada ingestão de cálcio, vitamina D e proteína leva à redução da remodelação óssea, à maior retenção de cálcio, à redução da perda óssea relacionada à idade e à redução do risco de fraturas. Evidências recentes indicam que uma alimentação saudável, incluindo a ingestão de produtos lácteos (principalmente os desnatados), frutas e verduras, e uma quantidade adequada de carnes, peixes e aves, está relacionada positivamente com a saúde óssea. Além disso, a suplementação de vitaminas e minerais deve ser monitorada de perto, por profissionais de saúde, uma vez que pode ter efeitos adversos e ser insuficiente para assegurar uma eficaz proteção à saúde óssea.Arq Bras Endocrinol Metab. 2010;54(2):179-85

A cytosolic isoform of renin with unknown functions is expressed in the heart. Cytosolic renin diminishes ischemia induced damage to the heart. The protective effects of cytosolic renin contradict the known function of secretory renin. The effects of cytosolic renin are not mediated via angiotensin generation. Renin-binding protein is a potential target for cytosolic renin.

A concomitant excessive consumption of sweet foods and caffeinated beverages appears to exert a negative effect on BMD even when the skeleton already presents some demineralization. Food and beverage intake is a modifiable factor that should not be neglected in the treatment of individuals with osteoporosis.

The majority of adolescents and young adults did not consume recommended intakes of calcium and vitamin D and also presented 25(OH)D insufficiency. The results indicate that a regular breakfast and the consumption of dairy products represent important strategies in improving calcium and vitamin D intake in the diet.