Genetic determinants of blood pressure and heart rate identified through ENU-induced mutagenesis with automated meiotic mapping.

We used N-ethyl-N-nitrosurea-induced germline mutagenesis combined with automated meiotic mapping to identify specific systolic blood pressure (SBP) and heart rate (HR) determinant loci. We analyzed 43,627 third-generation (G3) mice from 841 pedigrees to assess the effects of 45,378 variant alleles within 15,760 genes, in both heterozygous and homozygous states. We comprehensively tested 23% of all protein-encoding autosomal genes and found 87 SBP and 144 HR (with 7 affecting both) candidates exhibiting detectable hypomorphic characteristics. Unexpectedly, only 18 of the 87 SBP genes were previously known, while 26 of the 144 genes linked to HR were previously identified. Furthermore, we confirmed the influence of two genes on SBP regulation and three genes on HR control through reverse genetics. This underscores the importance of our research in uncovering genes associated with these critical cardiovascular risk factors and illustrate the effectiveness of germline mutagenesis for defining key determinants of polygenic phenotypes that must be studied in an intact organism.

Sympathetic and angiotensinergic activity in spontaneously hypertensive rats treated with 3-amino-1,2,4-triazole.

Previous studies from our laboratory have shown that the pressor response to intracerebroventricular (icv) administered ANG II in normotensive rats or spontaneously hypertensive rats (SHRs) is attenuated by increased central H2O2 concentration, produced either by direct H2O2 icv injection or by increased endogenous H2O2 centrally in response to local catalase inhibition with 3-amino-1,2,4-triazole (ATZ). In the present study, we evaluated the effects of ATZ administered peripherally on arterial pressure and sympathetic and angiotensinergic activity in SHRs. Male SHRs weighing 280-330 g were used. Mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious freely moving SHRs. Acute intravenous injection of ATZ (300 mg/kg of body weight) did not modify MAP and HR during the next 4 h, however, the treatment with ATZ (300 mg/kg of body weight twice per day) for 3 days reduced MAP (144 ± 6, vs. saline, 183 ± 13 mmHg), without changing HR. Intravenous hexamethonium (ganglionic blocker) produced a smaller decrease in MAP 4 h after ATZ (-25 ± 3, vs saline -38 ± 4 mmHg). Losartan (angiotensinergic AT1 receptor blocker) produced a significant depressor response 4 h after ATZ (-22 ± 4, vs. saline: -2 ± 4 mmHg) and in 3-day ATZ treated SHRs (-25 ± 5, vs. saline: -9 ± 4 mmHg). The results suggest that the treatment with ATZ reduces sympathetic activity in SHRs and simultaneously increases angiotensinergic activity.

Relative Contribution of Blood Pressure and Renal Sympathetic Nerve Activity to Proximal Tubular Sodium Reabsorption via NHE3 Activity.

We examined the effects of an acute increase in blood pressure (BP) and renal sympathetic nerve activity (rSNA) induced by bicuculline (Bic) injection in the paraventricular nucleus of hypothalamus (PVN) or the effects of a selective increase in rSNA induced by renal nerve stimulation (RNS) on the renal excretion of sodium and water and its effect on sodium-hydrogen exchanger 3 (NHE3) activity. Uninephrectomized anesthetized male Wistar rats were divided into three groups: (1) Sham; (2) Bic PVN: (3) RNS + Bic injection into the PVN. BP and rSNA were recorded, and urine was collected prior and after the interventions in all groups. RNS decreased sodium (58%) and water excretion (53%) independently of BP changes (p < 0.05). However, after Bic injection in the PVN during RNS stimulation, the BP and rSNA increased by 30% and 60% (p < 0.05), respectively, diuresis (5-fold) and natriuresis (2.3-fold) were increased (p < 0.05), and NHE3 activity was significantly reduced, independently of glomerular filtration rate changes. Thus, an acute increase in the BP overcomes RNS, leading to diuresis, natriuresis, and NHE3 activity inhibition.

Renal, Cardiac, and Autonomic Effects of Catheter-Based Renal Denervation in Ovine Heart Failure.

[Figure: see text].

Effects of physical exercise on baroreflex sensitivity and renal sympathetic nerve activity in chronic nicotine-treated rats.

Chronic nicotine exposure may increase cardiovascular risk by impairing the cardiac autonomic function. Besides, physical exercise (PE) has shown to improve cardiovascular health. Thus, we aimed to investigate the effects of PE on baroreflex sensitivity (BRS), heart rate variability (HRV), and sympathetic nerve activity (SNA) in chronically nicotine-exposed rats. Male Wistar rats were assigned to four independent groups: Control (treated with saline solution), Control+Ex (treated with saline and submitted to treadmill training), Nicotine (treated with Nicotine), and Nicotine+Ex (treated with nicotine and submitted to treadmill training). Nicotine (1 mg·kg-1) was administered daily for 28 consecutive days. PE consisted of running exercise (60%-70% of maximal aerobic capacity) for 45 min, 5 days per week, for 4 weeks. At the end of the protocol, cardiac BRS, HRV, renal SNA (rSNA), and renal BRS were assessed. Nicotine treatment decreased absolute values of HRV indexes, increased low frequency/high frequency ratio of HRV, reduced the bradycardic and sympatho-inhibitory baroreceptor reflex responses, and reduced the rSNA. PE effectively restored time-domain HRV indexes, the bradycardic and sympatho-inhibitory reflex responses, and the rSNA in chronic nicotine-treated rats. PE was effective in preventing the deterioration of time-domain parameters of HRV, arterial baroreceptor dysfunction, and the rSNA after nicotine treatment.

Renal Sensory Activity Regulates the γ-Aminobutyric Acidergic Inputs to the Paraventricular Nucleus of the Hypothalamus in Goldblatt Hypertension.

Renal sensory activity is centrally integrated within brain nuclei involved in the control of cardiovascular function, suggesting that renal afferents regulate basal and reflex sympathetic vasomotor activity. Evidence has shown that renal deafferentation (DAx) evokes a hypotensive and sympathoinhibitory effect in experimental models of cardiovascular diseases; however, the underlying mechanisms involved in this phenomenon need to be clarified, especially those related to central aspects. We aimed to investigate the role of renal afferents in the control of γ-aminobutyric acid (GABA)ergic inputs to the paraventricular nucleus (PVN) of the hypothalamus in renovascular hypertensive (2K1C) rats and their influence in the regulation of cardiovascular function. Hypertension was induced by clipping the left renal artery. After 4 weeks, renal DAx was performed by exposing the left renal nerve to a 33 mM capsaicin solution for 15 min. After 2 weeks of DAx, microinjection of muscimol into the PVN was performed in order to evaluate the influence of GABAergic activity in the PVN and its contribution to the control of renal sympathetic nerve activity (rSNA) and blood pressure (BP). Muscimol microinjected into the PVN triggered a higher drop in BP and rSNA in the 2K1C rats and renal DAx mitigated these responses. These results suggest that renal afferents are involved in the GABAergic changes found in the PVN of 2K1C rats. Although the functional significance of this phenomenon needs to be clarified, it is reasonable to speculate that GABAergic alterations occur to mitigate microglia activation-induced sympathoexcitation in the PVN of 2K1C rats.

Pattern of sympathetic vasomotor activity in a model of hypertension induced by nitric oxide synthase blockade.

We aimed to investigate the effects of nitric oxide (NO) synthesis inhibition by NO synthase inhibitor N-nitro-L-arginine-methyl ester (L-NAME) treatment on the sympathetic vasomotor nerve activity (SNA) on two sympathetic vasomotor nerves, the renal and splanchnic. NO plasma level and systemic oxidative stress were assessed. Hypertension was induced by L-NAME (20 mg/kg per day, by gavage, for seven consecutive days) in male Wistar rats. At the end of the treatment, blood pressure, heart rate, arterial baroreflex sensitivity, renal SNA (rSNA), and splanchnic SNA (sSNA) were assessed in urethane anesthetized rats. L-NAME-treated rats presented increased blood pressure (152 ± 2 mmHg, n = 17) compared to the control group (101 ± 2 mmHg, n = 15). Both rSNA (147 ± 10, n = 15 vs. 114 ± 5 Spikes/s, n = 9) and sSNA (137 ± 13, n = 14 vs. 74 ± 13 spikes/s, n = 9) were significantly increased in the L-NAME-treated compared to the control group. A differential response on baroreflex sensitivity was found, with a significant reduction for rSNA but not for sSNA arterial baroreceptor sensitivity in L-NAME-treated rats. The adjusted regression model revealed that the reduction of systemic NO levels partially explains the variation in sSNA and blood pressure, but not rSNA. Taken together, our data show that hypertension induced by NO synthase blockade is characterized by increased SNA to the rSNA and sSNA. In addition, we found that the rats that had the greatest reduction in NO levels in plasma by L-NAME were those that developed higher blood pressure levels. The reduction in the NO level partially explains the variations in sSNA but not in rSNA.

Melatonin attenuates renal sympathetic overactivity and reactive oxygen species in the brain in neurogenic hypertension.

Sympathetic overactivation contributes to the pathogenesis of both experimental and human hypertension. We have previously reported that oxidative stress in sympathetic premotor neurons leads to arterial baroreflex dysfunction and increased sympathetic drive to the kidneys in an experimental model of neurogenic hypertension. In this study, we hypothesized that melatonin, a potent antioxidant, may be protective in the brainstem regions involved in the tonic and reflex control of blood pressure (BP) in renovascular hypertensive rats. Neurogenic hypertension was induced by placing a silver clip (gap of 0.2 mm) around the left renal artery, and after 5 weeks of renal clip placement, the rats were treated orally with melatonin (30 mg/kg/day) by gavage for 15 days. At the end of melatonin treatment, we evaluated baseline mean arterial pressure (MAP), renal sympathetic nerve activity (rSNA), and the baroreflex control of heart rate (HR) and rSNA. Reactive oxygen species (ROS) were detected within the brainstem regions by dihydroethidium staining. Melatonin treatment effectively reduced baseline MAP and sympathoexcitation to the ischemic kidney in renovascular hypertensive rats. The baroreflex control of HR and rSNA were improved after melatonin treatment in the hypertensive group. Moreover, there was a preferential decrease in ROS within the rostral ventrolateral medulla (RVLM) and the nucleus of the solitary tract (NTS). Therefore, our study indicates that melatonin is effective in reducing renal sympathetic overactivity associated with decreased ROS in brainstem regions that regulate BP in an experimental model of neurogenic hypertension.

Blunted diuretic and natriuretic responses to acute sodium loading early after catheter-based renal denervation in normotensive sheep.

Catheter-based renal denervation (RDN) was introduced as a treatment for resistant hypertension. There remain critical questions regarding the physiological mechanisms underlying the hypotensive effects of catheter-based RDN. Previous studies indicate that surgical denervation reduces renin and the natriuretic response to saline loading; however, the effects on these variables of catheter-based RDN, which does not yield complete denervation, are largely unknown. The aim of this study was to investigate the effects of catheter-based RDN on glomerular-associated renin and regulation of fluid and sodium homeostasis in response to physiological challenges. First, immunohistochemical staining for renin was performed in normotensive sheep (n = 6) and sheep at 1 wk (n = 6), 5.5 mo (n = 5), and 11 mo (n = 5) after unilateral RDN using the same catheter used in patients (Symplicity). Following catheter-based RDN (1 wk), renin-positive glomeruli were significantly reduced compared with sham animals (P < 0.005). This was sustained until 5.5 mo postdenervation. To determine whether the reduction in renin after 1 wk had physiological effects, in a separate cohort, Merino ewes were administered high and low saline loads before and 1 wk after bilateral RDN (n = 9) or sham procedure (n = 8). After RDN (1 wk), the diuretic response to a low saline load was significantly reduced (P < 0.05), and both the diuretic and natriuretic responses to a high saline load were significantly attenuated (P < 0.05). In conclusion, these findings indicate that catheter-based RDN acutely alters the ability of the kidney to regulate fluid and electrolyte balance. Further studies are required to determine the long-term effects of catheter-based RDN on renal sodium and water homeostasis.

Stimulation of renal afferent fibers leads to activation of catecholaminergic and non-catecholaminergic neurons in the medulla oblongata.

Presympathetic neurons in the rostral ventrolateral medulla (RVLM) including the adrenergic cell groups play a major role in the modulation of several reflexes required for the control of sympathetic vasomotor tone and blood pressure (BP). Moreover, sympathetic vasomotor drive to the kidneys influence natriuresis and diuresis by inhibiting the cAMP/PKA pathway and redistributing the Na+/H+ exchanger isoform 3 (NHE3) to the body of the microvilli in the proximal tubules. In this study we aimed to evaluate the effects of renal afferents stimulation on (1) the neurochemical phenotype of Fos expressing neurons in the medulla oblongata and (2) the level of abundance and phosphorylation of NHE3 in the renal cortex. We found that electrical stimulation of renal afferents increased heart rate and BP transiently and caused activation of tyrosine hydroxylase (TH)-containing neurons in the RVLM and non-TH neurons in the NTS. Additionally, activation of the inhibitory renorenal reflex over a 30-min period resulted in increased natriuresis and diuresis associated with increased phosphorylation of NHE3 at serine 552, a surrogate for reduced activity of this exchanger, in the contralateral kidney. This effect was not dependent of BP changes considering that no effects on natriuresis or diuresis were found in the ipsilateral-stimulated kidney. Therefore, our data show that renal afferents leads to activation of catecholaminergic and non-catecholaminergic neurons in the medulla oblongata. When renorenal reflex is induced, NHE3 exchanger activity appears to be decreased, resulting in decreased sodium and water reabsorption in the contralateral kidney.

The antioxidant effects of green tea reduces blood pressure and sympathoexcitation in an experimental model of hypertension.

BACKGROUND: Oxidative stress is a key mediator in the maintenance of sympathoexcitation and hypertension in human and experimental models. Green tea is widely known to be potent antioxidant. OBJECTIVE: We aimed to evaluate the effects of green tea in a model of hypertension. METHODS: Hypertension was induced by the nitric oxide synthase inhibitor [N-nitro-L-arginine-methyl-ester (L-NAME); 20 mg/kg per day, orally, for 2 weeks] in male Wistar rats. After the first week of L-NAME treatment, animals received green tea ad libitum for 1 week. At the end of the treatment period, blood pressure, heart rate, baroreflex sensitivity, renal sympathetic nerve activity, and vascular and systemic oxidative stress were assessed. RESULTS: L-NAME-treated animals exhibited an increase in blood pressure (165 ±â€Š2 mmHg) compared with control rats (103 ±â€Š1 mmHg) and green tea treatment reduced hypertension (119 ±â€Š1 mmHg). Hypertensive animals showed a higher renal sympathetic nerve activity (161 ±â€Š12 spikes/s) than the control group (97 ±â€Š2 spikes/s), and green tea also decreased this parameter in the hypertensive treated group (125 ±â€Š5 spikes/s). Arterial baroreceptor function and vascular and systemic oxidative stress were improved in hypertensive rats after green tea treatment. CONCLUSIONS: Taken together, short-term green tea treatment improved cardiovascular function in a hypertension model characterized by sympathoexcitation, which may be because of its antioxidant properties.

Chronic Nicotine Exposure Abolishes Maternal Systemic and Renal Adaptations to Pregnancy in Rats.

Pregnancy is characterized by maternal systemic and intrarenal vasodilation, leading to increases in the renal plasma flow (RPF) and glomerular filtration rate (GFR). These responses are mainly mediated by nitric oxide (NO) and relaxin. The impact of cigarette smoking on the maternal adaptations to pregnancy is unclear. Here we evaluated the effects of chronic exposure to nicotine on systemic and intrarenal parameters in virgin (V) and 14-day pregnant (P) Wistar rats. V and P groups received saline or nicotine (6 mg·kg(-1)·day(-1)) respectively, via osmotic minipumps for 28 days, starting 14 days before pregnancy induction. Nicotine induced a 10% increase in blood pressure in the V group and minimized the characteristic pregnancy-induced hypotension. Renal sympathetic nerve activity (rSNA) and baroreflex sensitivity were impaired by nicotine mainly in the P group, indicating that the effect of nicotine on blood pressure was not mediated by nervous system stimulation. Nicotine had no effect on GFR in the V rats but reduced GFR of the P group by 30%. Renal expression of sodium and water transporters was downregulated by nicotine, resulting in increased fractional sodium excretion mainly in the P group, suggesting that nicotine compromised the sodium and water retention required for normal gestation. There was a reduction in the expression of inducible NO synthase (iNOS) in both the kidney tissue and renal artery, as well as in the expression of the relaxin receptor (LGR7). These results clearly show that nicotine induced deleterious effects in both virgin and pregnant animals, and abolished the maternal capacity to adapt to pregnancy.

Crosstalk between the renal sympathetic nerve and intrarenal angiotensin II modulates proximal tubular sodium reabsorption.

NEW FINDINGS: What is the topic of this review? The sympathetic control of renal sodium tubular reabsorption is dependent on activation of the intrarenal renin-angiotensin system and activation of the angiotensin II type 1 (AT1 ) receptor by angiotensin II. What advances does it highlight? Despite the fact that the interaction between the sympathetic nervous system and angiotensin II regarding salt reabsorption is a well-known classical mechanism for the maintenance of extracellular volume homeostasis, the underlying molecular signalling is not clearly understood. It has been shown recently that renal nerve stimulation increases intrarenal angiotensin II and activates the AT1 receptor, triggering a signalling cascade that leads to elevations of Na(+) -H(+) exchanger isoform 3-mediated tubular transport. In this short review, the crosstalk between intrarenal angiotensin II and renal nerve activity and its effect on sodium reabsorption is addressed. In this review, we address the importance of the interaction between the sympathetic nervous system and intrarenal renin-angiotensin system in modulating renal tubular handling of sodium and water. We have recently shown that increased Na(+) -H(+) exchanger isoform 3 (NHE3) activity induced by renal nerve stimulation (RNS) depends on the activation of the angiotensin II type 1 (AT1 ) receptor by angiotensin II (Ang II). Low-frequency RNS resulted in higher levels of intrarenal angiotensinogen and Ang II independent of changes in blood pressure, the glomerular filtration rate and systemic angiotensinogen. Angiotensin II, via the AT1 receptor, triggered an intracellular pathway activating NHE3 in the renal cortex, leading to antinatriuresis and antidiuresis. Pharmacological blockade of the AT1 receptor with losartan prior to RNS abolished both the functional and the molecular responses, suggesting that intrarenal Ang II acting via the AT1 receptor is a major factor for NHE3-mediated sodium and water reabsorption induced by RNS.

Renal nerve stimulation leads to the activation of the Na+/H+ exchanger isoform 3 via angiotensin II type I receptor.

Renal nerve stimulation at a low frequency (below 2 Hz) causes water and sodium reabsorption via α1-adrenoreceptor tubular activation, a process independent of changes in systemic blood pressure, renal blood flow, or glomerular filtration rate. However, the underlying mechanism of the reabsorption of sodium is not fully understood. Since the sympathetic nervous system and intrarenal ANG II appear to act synergistically to mediate the process of sodium reabsorption, we hypothesized that low-frequency acute electrical stimulation of the renal nerve (ESRN) activates NHE3-mediated sodium reabsorption via ANG II AT1 receptor activation in Wistar rats. We found that ESRN significantly increased urinary angiotensinogen excretion and renal cortical ANG II content, but not the circulating angiotensinogen levels, and also decreased urinary flow and pH and sodium excretion via mechanisms independent of alterations in creatinine clearance. Urinary cAMP excretion was reduced, as was renal cortical PKA activity. ESRN significantly increased NHE3 activity and abundance in the apical microvillar domain of the proximal tubule, decreased the ratio of phosphorylated NHE3 at serine 552/total NHE3, but did not alter total cortical NHE3 abundance. All responses mediated by ESRN were completely abolished by a losartan-mediated AT1 receptor blockade. Taken together, our results demonstrate that higher NHE3-mediated proximal tubular sodium reabsorption induced by ESRN occurs via intrarenal renin angiotensin system activation and triggering of the AT1 receptor/inhibitory G-protein signaling pathway, which leads to inhibition of cAMP formation and reduction of PKA activity.

Análise dos aspectos epidemiológicos dos candidatos à doação de órgãos no Estado do Pará / Analysis of the epidemiological aspects of candidates for organ donation in the state of Pará

JUSTIFICATIVA E OBJETIVOS: A fila para transplante de alguns órgãos é quase seis vezes maior que o número de implantes realizados, sendo uma realidade alarmante e progressiva, com isso objetivou-se analisar aspectos epidemiológicos dos candidatos à doação de órgãos no estado do Pará.MÉTODO: Estudo transversal, com todo potencial doador no Pará, de acordo com o Registro Brasileiro de Transplantes. Baseados no dendrograma foram escolhidos São Paulo e Acre como extremos opostos de desempenho para comparação.RESULTADOS: Foi observado que o número de potenciais doadores,em pmp/ano, no Pará foi 15,4, no Acre 15 e em São Paulo60,5. Dentre as causas de não concretização, a não aceitação familiar no Pará representou 56% do total, no Acre 43% e em São Paulo 39%. Setenta e seis por cento dos doadores paraenses eram do sexo masculino, 42,3% tinham idade entre 18 e 40 anos e 57,7% vítimas de traumatismo cranioencefálico sendo o perfil dos candidatos paraenses.CONCLUSÃO: O desempenho em São Paulo foi muito superior ao dos outros em todos os aspectos, sendo que o principal motivo para não concretização da doação em todos os estados foi negação familiar.

BACKGROUND AND OBJECTIVES: The queue for some organs transplant is almost six times greater than the number of implants performed, being an alarming and progressive situation; therefore, this study aimed to analyze epidemiological aspects of candidates for organ donation in the state of Pará. METHOD: A cross-sectional study was performed, with all potential donors in Pará, according to the Brazilian Registry of Transplants. Based on the dendrogram, the states of Sao Paulo and Acre were chosen as opposite extremes of performance for comparison. RESULTS: We found that the number of potential donors, pmp/year, was of 15.4 in the state of Pará, 15 in the state of Acre and 60.5 in São Paulo. Among the causes for no achievement, no acceptance by the family was of 56% of the total in Pará, 43% in Acre and 39% in São Paulo. Seventy six per cent of donors from Pará were male, 42.3% were between 18 and 40 years of age and 57.7% were victims of traumatic brain injury, this being the profile of the candidates from Pará.CONCLUSION: The performance in São Paulo was far superior to the others in all aspects, with the family denial being the main reason for not accomplishing the donation in all states.

Efeito do ultrassom terapêutico de baixa intensidade em fratura induzida em tíbia de ratos / The effect of low-intensity therapeutic ultrasound in induced fracture of rat tibiae

Objetivo: Averiguar os possíveis efeitos do ultrassom de baixa intensidade, utilizado em tratamentos fisioterapêuticos de rotina, em fratura induzida em tíbia de ratos. Métodos: Foram utilizados 20 ratos machos Wistar , distribuídos em 2 grupos, com 10 animais, cada. No grupo ultrassom (GUS), os animais sofreram fratura óssea e tratamento com ultrassom terapêutico (UST) a 1,0 MHz e intensidade de 0,2 W/cm2, no modo pulsado a 20%, aplicado de forma estacionária, por 10 minutos, na região da fratura, durante cinco semanas. O grupo controle (GC) sofreu fratura óssea e não foi tratado com UST. Resultados: Nas radiografias, observou-se melhor consolidação no GUS em relação ao GC. Já na análise de fosfatase alcalina (FALC) e cálcio sérico (CS), não se evidenciou efeito estatisticamente significativo. Conclusão: De acordo com o presente estudo, o UST aplicado conforme esses parâmetros promoveu aceleração da consolidação, comprovada por radiografia, entretanto a análise bioquímica não foi conclusiva. Um dos motivos para essa divergência pode ter sido alguma inadequação do protocolo bioquímico, atualmente em investigação. Nível de Evidência II, Estudo prospectivo comparativo.

Objective: To analyze the possible effects of low-intensity ultrasound on induced tibia fracture of rats in a dose commonly used in physical therapy treatments. Methods: Twenty male Wistar rats were divided into two groups with 10 animals each. In the ultrasound group (USG), the animals were submitted to bone fracture and treatment with therapeutic ultrasound (TUS). Ultrasonic parameters are: frequency of 1.0 MHz, intensity of 0.2 W/cm2, pulsed mode at 20%, applied in stationary form during 10 minutes on the fracture region, for five weeks. The control group (CG) was submitted to bone fracture but not treated with ultrasound. Results: The radiographies showed better consolidation in USG compared to CG. The statistical tests for alkaline phosphatase and serum calcium did not show significant difference between groups. Conclusion: According to this study, TUS, applied with these parameters (not commonly used for bone therapy) accelerates bone healing, confirmed by radiography, yet the biochemical analysis was not conclusive. One reason for this inconsistency may have been some inadequacy of the biochemical protocol,currently under investigation. Level of Evidence II, Prospective comparative study.

The effect of low-intensity therapeutic ultrasound in induced fracture of rat tibiae.

OBJECTIVE: To analyze the possible effects of low-intensity ultrasound on induced tibia fracture of rats in a dose commonly used in physical therapy treatments. METHODS: Twenty male Wistar rats were divided into two groups with 10 animals each. In the ultrasound group (USG), the animals were submitted to bone fracture and treatment with therapeutic ultrasound (TUS). Ultrasonic parameters are: frequency of 1.0 MHz, intensity of 0.2 W/cm2, pulsed mode at 20%, applied in stationary form during 10 minutes on the fracture region, for five weeks. The control group (CG) was submitted to bone fracture but not treated with ultrasound. RESULTS: The radiographies showed better consolidation in USG compared to CG. The statistical tests for alkaline phosphatase and serum calcium did not show significant difference between groups. CONCLUSION: According to this study, TUS, applied with these parameters (not commonly used for bone therapy) accelerates bone healing, confirmed by radiography, yet the biochemical analysis was not conclusive. One reason for this inconsistency may have been some inadequacy of the biochemical protocol, currently under investigation. Level of Evidence II, Prospective comparative study.

Blood pressure reducing effects of Phalaris canariensis in normotensive and spontaneously hypertensive rats.

The birdseed Phalaris canariensis (Pc) is popularly used as an antihypertensive agent. The aqueous extract of Pc (AEPc) was administered in adult normotensive Wistar rats and spontaneously hypertensive rats (SHR) and in prehypertensive young SHR (SHR(Y), 3 weeks old). Animals received AEPc (400 mg·kg(-1)·day(-1), by gavage) for 30 days, then groups were divided into 2 subgroups: one was treated for another 30 days and the other received water instead of AEPc for 30 days. AEPc reduced systolic blood pressure (SBP) in both adult groups; however, treatment interruption was followed by a gradual return of the SBP to baseline levels. SHR(Y) became hypertensive 30 days after weaning. AEPc minimized the increase in SBP in SHR(Y), but blood pressure rose to levels similar to those in the untreated group with treatment interruption. There were no changes in renal function, diuresis, or Na(+) excretion. Pc is rich in tryptophan, and the inhibition of the metabolism of tryptophan to kynurenine, a potential vasodilator factor, prevented the blood pressure reducing effect of AEPc. Moreover, AEPc significantly reduced sympathoexcitation. Data indicate that the metabolic derivative of tryptophan, kynurenine, may be a mediator of the volume-independent antihypertensive effect of Pc, which was at least in part mediated by suppression of the sympathetic tonus.

Análise dos motivos para não doação de órgãos em hospital de referência na Amazônia / Analysis of reasons for denial for organ donation in a referral hospital in the Amazon region

Objetivo: analisar os motivos para não doação de órgãos em hospital de referência na Amazônia. Método: foi realizado um estudo transversal, com os pacientes do Hospital Metropolitano de Urgência e Emergência, após declaração de morte cerebral. Resultados: observamos que no hospital metropolitano, 65% das famílias foram abordadas, porém 73% destas não permitiram a doação, sendo 68% das recusas pelo desejo de manutenção do corpo íntegro. Conclusão: no hospital metropolitano, a justificativa principal de negação familiar da doação foi o desejo do corpo íntegro. A não abordagem familiar foi devido à contraindicação médica ou impossibilidade de localizar a família em tempo hábil.

Histological analysis of low-intensity laser therapy effects in peripheral nerve regeneration in Wistar rats / Avaliação histológica dos efeitos da laserterapia de baixa potência sobre os processos de regeneração nervosa periférica em ratos Wistar

Purpose: Analyze the influence of low-intensity laser therapy in the sciatic nerve regeneration of rats submitted to controlled crush through histological analysis. Methods: Were used 20 Wistar rats, to analyze the influence of low-intensity laser therapy in the sciatic nerve regeneration, where the injury of the type axonotmesis was induced by a haemostatic clamp Crile (2nd level of the rack). The animals were randomly distributed in 2 groups. Control group (CG n = 10) and Laser group (LG n = 10). These were subdivided in 2 subgroups each, according to the euthanasia period: (CG14 _ n = 5 and CG21 _ n = 5) and (LG14 _ n = 5 and LG21 _ n = 5). At the end of treatment, the samples were removed and prepared for histological analysis, where were analyzed and quantified the following findings: Schwann cells, myelinic axons with large diameter and neurons. Results: In the groups submitted to low-intensity laser therapy, were observed an increase in the number of all analyzed aspects with significance level. Conclusion: The irradiation with low intensity laser (904nm) influenced positively the regeneration of the sciatic nerve in Wistar rats after being injured by crush (axonotmesis), becoming the nerve recovery more rapid and efficient.

Objetivo: Verificar a influência da terapia com laser de baixa potência na regeneração histológica do nervo ciático de ratos submetidos à neuropraxia controlada. Métodos: Foi utilizada a amostra de 20 ratos da linhagem Wistar, para verificar a influência da terapia com laser de baixa intensidade na regeneração nervosa periférica, onde a lesão do tipo axoniotmese foi induzida por meio de preensão com pinça hemostática de Crile. Os animais foram distribuídos randomicamente dois grupos. Grupo controle (CG n = 10), e Grupo laser (LG n = 10). Cada um destes grupos foi subdividido em dois subgrupos dependendo do período da eutanásia: (CG14 - n = 5 e CG21 - n = 5) e (LG14 - n = 5 e LG21 - n = 5). Ao final do tratamento, amostras do nervo foram retiradas e analisadas histologicamente, nas quais foi adotado na pesquisa a análise do número de neurônios, de células de Schwann (CS) e de axônios mielínicos de grande diâmetro. Resultados: Nos grupos submetidos à terapia com laser de baixa potencia foi observado aumento do número de todos os aspectos analisados com diferença estatisticamente significante. Conclusão: A irradiação com o laser de baixa intensidade (904nm) influenciou positivamente na regeneração do nervo ciático de ratos da linhagem Wistar pós neuropraxia controlada (axonotmese), tornando a recuperação nervosa mais rápida e eficiente.