Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

Hormone therapy with tamoxifen reduces plasma levels of NT-B-type natriuretic peptide but does not change ventricular ejection fraction after chemotherapy in women with breast cancer

The objective of this study was to evaluate the effect of tamoxifen on the plasma concentration of NT-pro-B-type natriuretic peptide (NT-proBNP) in women undergoing chemotherapy for breast cancer and to correlate changes in NT-proBNP with the left ventricular ejection fraction (LVEF). Over a period of 12 months, we followed 60 women with a diagnosis of breast cancer. The patients were separated into a group that received only chemotherapy (n=23), a group that received chemotherapy + tamoxifen (n=21), and a group that received only tamoxifen (n=16). Plasma levels of NT-proBNP were assessed at 0 (T0), 6 (T6), and 12 (T12) months of treatment, and echocardiography data were assessed at T0 and T12. Plasma NT-proBNP levels were increased in the chemotherapy-only group at T6 and T12, whereas elevated NT-proBNP levels were only found at T6 in the chemotherapy + tamoxifen group. At T12, the chemotherapy + tamoxifen group exhibited a significant reduction in the peptide to levels similar to the group that received tamoxifen alone. The chemotherapy-only group exhibited a significant decrease in LVEF at T12, whereas the chemotherapy + tamoxifen and tamoxifen-only groups maintained levels similar to those at the beginning of treatment. Treatment with tamoxifen for 6 months after chemotherapy significantly reduced the plasma levels of NT-proBNP and did not change LVEF in women with breast cancer.

Combined aliskiren and L-arginine treatment has antihypertensive effects and prevents vascular endothelial dysfunction in a model of renovascular hypertension

Angiotensin II is a key player in the pathogenesis of renovascular hypertension, a condition associated with endothelial dysfunction. We investigated aliskiren (ALSK) and L-arginine treatment both alone and in combination on blood pressure (BP), and vascular reactivity in aortic rings. Hypertension was induced in 40 male Wistar rats by clipping the left renal artery. Animals were divided into Sham, 2-kidney, 1-clip (2K1C) hypertension, 2K1C+ALSK (ALSK), 2K1C+L-arginine (L-arg), and 2K1C+ALSK+L-arginine (ALSK+L-arg) treatment groups. For 4 weeks, BP was monitored and endothelium-dependent and independent vasoconstriction and relaxation were assessed in aortic rings. ALSK+L-arg reduced BP and the contractile response to phenylephrine and improved acetylcholine relaxation. Endothelium removal and incubation with N-nitro-L-arginine methyl ester (L-NAME) increased the response to phenylephrine in all groups, but the effect was greater in the ALSK+L-arg group. Losartan reduced the contractile response in all groups, apocynin reduced the contractile response in the 2K1C, ALSK and ALSK+L-arg groups, and incubation with superoxide dismutase reduced the phenylephrine response in the 2K1C and ALSK groups. eNOS expression increased in the 2K1C and L-arg groups, and iNOS was increased significantly only in the 2K1C group compared with other groups. AT1 expression increased in the 2K1C compared with the Sham, ALSK and ALSK+L-arg groups, AT2 expression increased in the ALSK+L-arg group compared with the Sham and L-arg groups, and gp91phox decreased in the ALSK+L-arg group compared with the 2K1C and ALSK groups. In conclusion, combined ALSK+L-arg was effective in reducing BP and preventing endothelial dysfunction in aortic rings of 2K1C hypertensive rats. The responsible mechanisms appear to be related to the modulation of the local renin-angiotensin system, which is associated with a reduction in endothelial oxidative stress.

Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

The maintenance of extracellular Na+ and Cl- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na+ and Cl- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg-1·day-1, sc) and progesterone (OVP, 1.7 mg·kg-1·day-1, sc). We assessed Na+ and Cl- fractional excretion (FENa+ and FECl- , respectively) and renal and plasma catecholamine release concentrations. FENa+ , FECl- , water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FENa+ , FECl- , water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function.

The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV = 12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-α) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects.

Sertraline inhibits formalin-induced nociception and cardiovascular responses

The objective of the present study was to determine the antihyperalgesic effect of sertraline, measured indirectly by the changes of sciatic afferent nerve activity, and its effects on cardiorespiratory parameters, using the model of formalin-induced inflammatory nociception in anesthetized rats. Serum serotonin (5-HT) levels were measured in order to test their correlation with the analgesic effect. Male Wistar rats (250-300 g) were divided into 4 groups (N = 8/per group): sertraline-treated group (Sert + Saline (Sal) and Sert + Formalin (Form); 3 mg·kg-1·day-1, ip, for 7 days) and saline-treated group (Sal + Sal and Sal + Form). The rats were injected with 5 percent (50 µL) formalin or saline into the right hind paw. Sciatic nerve activity was recorded using a silver electrode connected to a NeuroLog apparatus, and cardiopulmonary parameters (mean arterial pressure, heart rate and respiratory frequency), assessed after arterial cannulation and tracheotomy, were monitored using a Data Acquisition System. Blood samples were collected from the animals and serum 5-HT levels were determined by ELISA. Formalin injection induced the following changes: sciatic afferent nerve activity (+50.8 ± 14.7 percent), mean arterial pressure (+1.4 ± 3 mmHg), heart rate (+13 ± 6.8 bpm), respiratory frequency (+4.6 ± 5 cpm) and serum 5-HT increased to 1162 ± 124.6 ng/mL. Treatment with sertraline significantly reduced all these parameters (respectively: +19.8 ± 6.9 percent, -3.3 ± 2 mmHg, -13.1 ± 10.8 bpm, -9.8 ± 5.7 cpm) and serum 5-HT level dropped to 634 ± 69 ng/mL (P < 0.05). These results suggest that sertraline plays an analgesic role in formalin-induced nociception probably through a serotonergic mechanism.

Effect of tamoxifen on the coronary vascular reactivity of spontaneously hypertensive female rats

Tamoxifen has been associated with a reduction in the incidence of myocardial infarction. However, the effects of tamoxifen on coronary reactivity have not been fully elucidated. The objective of this study was to determine the effects of chronic treatment with tamoxifen on coronary vascular reactivity in spontaneously hypertensive rats (SHR). Female SHR were divided into four groups (N = 7 each): sham-operated (SHAM), sham-operated and treated with tamoxifen (10 mg/kg) by gavage for 90 days (TAMOX), ovariectomized (OVX), and ovariectomized and treated with tamoxifen (OVX+TAMOX). Mean arterial pressure (MAP), heart rate (HR), coronary perfusion pressure (CPP), and coronary vascular reactivity were measured. MAP and HR were reduced (9.42 and 11.67 percent, respectively) in the OVX+TAMOX group compared to the OVX group (P < 0.01). The coronary vascular reactivity of the OVX+TAMOX group presented smaller vasoconstrictor responses to acetylcholine (2-64 µg) when compared to the OVX group (P < 0.01) and this response was similar to that of the SHAM group. The adenosine-induced vasodilator response was greater in the TAMOX group compared to the SHAM and OVX groups (P < 0.05). Baseline CPP was higher in OVX+TAMOX and TAMOX groups (136 ± 3.6 and 130 ± 1.5 mmHg) than in OVX and SHAM groups (96 ± 2 and 119 ± 2.3 mmHg; P < 0.01). Tamoxifen, when combined with OVX, attenuated the vasoconstriction induced by acetylcholine and increased the adenosine-induced vasodilatory response, as well as reducing the MAP, suggesting beneficial effects of tamoxifen therapy on coronary vascular reactivity after menopause.

Influence of renal denervation on blood pressure, sodium and water excretion in acute total obstructive apnea in rats

Obstructive apnea (OA) can exert significant effects on renal sympathetic nerve activity (RSNA) and hemodynamic parameters. The present study focuses on the modulatory actions of RSNA on OA-induced sodium and water retention. The experiments were performed in renal-denervated rats (D; N = 9), which were compared to sham (S; N = 9) rats. Mean arterial pressure (MAP) and heart rate (HR) were assessed via an intrafemoral catheter. A catheter was inserted into the bladder for urinary measurements. OA episodes were induced via occlusion of the catheter inserted into the trachea. After an equilibration period, OA was induced for 20 s every 2 min and the changes in urine, MAP, HR and RSNA were recorded. Renal denervation did not alter resting MAP (S: 113 ± 4 vs D: 115 ± 4 mmHg) or HR (S: 340 ± 12 vs D: 368 ± 11 bpm). An OA episode resulted in decreased HR and MAP in both groups, but D rats showed exacerbated hypotension and attenuated bradycardia (S: -12 ± 1 mmHg and -16 ± 2 bpm vs D: -16 ± 1 mmHg and 9 ± 2 bpm; P < 0.01). The basal urinary parameters did not change during or after OA in S rats. However, D rats showed significant increases both during and after OA. Renal sympathetic nerve activity in S rats increased (34 ± 9 percent) during apnea episodes. These results indicate that renal denervation induces elevations of sodium content and urine volume and alters bradycardia and hypotension patterns during total OA in unconscious rats.

Implicações da lipoclasia dermossônica no metabolismo energético e na composição corporal de ratos Wistar saudáveis / Implications of dermosonic lipoclasis for energy metabolism and body composition of healthy Wistar rats

OBJETIVOS: Investigar as implicações da lipoclasia dermossônica (LCD), lipólise do tecido adiposo branco subcutâneo induzido por ultrassom (US), no metabolismo energético e na composição corporal de ratos saudáveis. MÉTODOS: Utilizaram-se 20 ratos Wistar saudáveis, com 4 meses de idade, pesando ±380g, divididos aleatoriamente em 2 grupos: 1) controle-sham (CS), 2) terapia ultrassônica de baixa intensidade (TUSBI). Durante 10 dias, após sedação (halotano-3 por cento vaporizado), os animais eram submetidos à TUSBI (I SATA=3MHz, 1W.cm-2, modo pulsado 2:8ms, ciclo de 30 por cento por 3 minutos) em região infra-abdominal e inguinal. Medidas de peso, comprimento naso-anal e parâmetros metabólicos (ingestão e excreção) foram controlados durante o estudo. Ao final do tratamento, amostras de sangue foram coletadas para dosagens bioquímicas, e então avaliadas adiposidades retroperitoneal (RET), perirenal (PR), epididimal (EP) e inguinal (ING). O HOMA-IR (homeostasis model assessment) foi calculado para estimar resistência insulínica (RI). Para análise estatística, utilizou-se ANOVA, teste de Tukey e teste t de Student, com diferenças estabelecidas em p<0,05. RESULTADOS: No peso corporal, não houve alteração nos animais CS (384±9g), no entanto reduziu (p<0,01) no grupo TUSBI (337±2g), assim como a ingestão de comida (25±1g) vs.(21±1g). Houve ainda reduções (p<0,05) nos coxins RET, PR e ING, índice de obesidade, níveis de triglicerídeos e lipoproteínas plasmáticas. A hiperinsulinemia, sem alterações da glicemia, caracterizou estado de RI confirmado pelo HOMA-IR. CONCLUSÕES: A LDC reduziu a ingestão de comida e o peso corporal, além de modificar a deposição de gordura nos depósitos RET, PR e ING em ratos, o que alterou o perfil lipoprotéico produzindo importante quadro de RI.

OBJECTIVES: To investigate the implications of Dermosonic lipoclasis (DLC), i.e. lipolysis on subcutaneous white adipose tissue induced by ultrasound, for the energy metabolism and body composition of healthy rats. METHODS: Twenty four-month-old male Wistar rats weighting ±380g were randomly divided into two groups: 1) sham control (SC) and 2) low-intensity ultrasound therapy (LIUST). For 10 days, after sedation with 3 percent vaporized halothane, the animals underwent LIUST (I SATA =3MHz, 1 Wcm-2, pulsed mode 2:8ms, 30 percent cycles for 3 minutes) in the infra-abdominal and inguinal regions. Weight measurements, naso-anal length and metabolic parameters (food and water intake and excretion) were monitored during the study. At the end of the treatment, blood samples were collected for biochemical analyses. Retroperitoneal (RET), perirenal (PR), epididymal (EP) and inguinal (ING) adiposity was evaluated. HOMA-IR (homeostasis model assessment) was calculated to estimate insulin resistance. For statistical analyses, the Student t test, ANOVA and the Tukey test were used, and differences were established as p<0.05. RESULTS: Regarding body weight, the SC group (384±9g) did not show any changes, while the treated group (337±2g) showed reductions (p<0.01). This was also seen in relation to food intake: (25±1g) vs. (21±1g). There were also reductions (p<0.05) in the RET, PR and ING fat-pads, obesity index, triglyceride levels and plasma lipoprotein levels. Hyperinsulinemia without changes in glycemia characterized a state of insulin resistance, which was confirmed by HOMA-IR. CONCLUSIONS: DLC reduced the food intake and body weight and modified the fat deposition in the RET, PR and ING stores in rats. This changed the lipid profile to produce a significant state of insulin resistance.

Efeitos da crioterapia, estimulação elétrica transcutânea e da sua associação na atividade elétrica do nervo femoral em ratos / Effects of cryotherapy, transcutaneous electrical stimulation and their combination on femoral nerve electrical activity in rats

CONTEXTUALIZAÇÃO: Relatos clínicos sugerem que a associação terapêutica entre crioterapia (CRIO) e estimulação elétrica transcutânea (TENS) favorece analgesia local. OBJETIVO: Avaliar a atividade elétrica do nervo femoral (ANF), em repouso e durante a aplicação isolada, e associada de TENS e CRIO em ratos. MÉTODOS: Foram utilizados nove ratos (Wistar) adultos com peso de ±300g. Após anestesia (Uretana, 1mg/g i.p.), o nervo femoral direito foi isolado para registro da ANF basal e durante as modalidades analgésicas. Depois da fixação dos eletrodos no terço inferior da coxa direita, foram aplicadas TENS (50Hz, 10mÅ) por cinco minutos, CRIO isolada e terapia associada (TA) por dez minutos. Os registros contínuos da ANF foram realizados por meio de um amplificador de potenciais de ação, avaliados posteriormente no primeiro, quinto e décimo minuto em unidades arbitrárias (Ua). Utilizaram-se a análise de variância (ANOVA) uma via e o teste de Dunnett como post-hoc. Valores expressos como média ±EPM e as diferenças fixadas em p<0,05. RESULTADOS: A atividade do nervo femoral aumentou (p<0,01) na TENS (0,358±0,09Ua) e na TA (0,230±0,07Ua) e ficou inalterada após CRIO (0,063±0,003Ua), em relação ao basal inicial (0,009±0,0003Ua). No quinto minuto, observou-se uma significante (p<0,05) atenuação da ANF na modalidade TA (0,144±0,027Ua) versus TENS isolada (0,324±0,089Ua). CONCLUSÕES: A associação entre as modalidades analgésicas não-invasivas CRIO e TENS atenua significativamente os efeitos produzidos pela TENS isoladamente sobre a ANF de ratos anestesiados.

BACKGROUND: Clinical reports suggest that the therapeutic association between cryotherapy (CRYO) and transcutaneous electrical stimulation (TENS) favors local analgesia. OBJECTIVE: To evaluate the electrical activity of the femoral nerve (FNA), at rest and during single and combined application of TENS and CRYO, in rats. METHODS: Nine adult Wistar rats weighting ±300g were used in this study. After inducing anesthesia (Urethane, 1mg/g i.p.), the right femoral nerve was isolated in order to record the FNA at baseline and during the therapeutic modalities. After attaching the electrodes to the lower third of the right thigh, TENS (50Hz, 10mÅ) was applied for five minutes, and CRYO and the combined therapy (CT) for ten minutes. The FNA was recorded continuously by means of an action potential amplifier and the recordings from the first, fifth and tenth minutes were subsequently evaluated using arbitrary units (aU). One-way analysis of variance (ANOVA) was used, with Dunnett's test as post-hoc analysis. The values were expressed as the mean ±SEM and differences were established at p<0.05. RESULTS: The femoral nerve activity increased (p<0.01) after TENS (0.358±0.09aU) and CT (0.230±0.07aU) and was unchanged after CRYO (0.063±0.003aU), in relation to the baseline (0.009±0.0003aU). In the fifth minute, we observed significant (p<0.05) attenuation of FNA in the CT (0.144±0.027aU) in relation to TENS alone (0.324±0.089aU). CONCLUSIONS: The association between CRYO and TENS noninvasive analgesia significantly attenuates the effects produced by TENS alone on the FNA of anesthetized rats.

Cardiovascular risk factors in a population of Brazilian schoolchildren

Epidemiological and clinical evidence suggests that a judicious diet, regular physical activity and blood pressure (BP) monitoring must start in early childhood to minimize the impact of modifiable cardiovascular risk factors. This study was designed to evaluate BP and metabolic parameters of schoolchildren from Vitória, Espírito Santo State, Brazil, and correlate them with cardiovascular risk factors. The study was conducted on 380 students aged 10-14 years (177 boys, 203 girls) enrolled in public schools. Baseline measurements included body mass index, BP and heart rate. The students were submitted to exercise spirometry on a treadmill. VO2max was obtained from exercise testing to voluntary exhaustion. Fasting serum total cholesterol (TC), LDL-C, HDL-C, triglycerides (TG), and glucose were measured. Nine point nine percent of the boys and 11.7 percent of the girls were hypertensive or had pre-hypertensive levels. There was no significant correlation between VO2max and TC, LDL-C, or TG in prepubertal children, but a slight negative correlation was detected in post-pubertal boys for HDL-C and TG. In addition, children with hypertension (3.4 percent) or pre-hypertensive levels (6.6 percent) also had comorbidity for overweight and blood lipid abnormalities (14 percent for triglycerides, 44.7 percent for TC, 25.9 percent for LDL-C, 52 percent for low HDL-C). The present study shows for the first time high correlations between prehypertensive blood pressure levels and the cardiovascular risk factors high TC, high LDL-C, low HDL-C in schoolchildren. These are important for the formulation of public health policies and strategies.

Endothelial mediators of 17á-estradiol-induced coronary vasodilation in the isolated rat heart

The present study was designed to determine relaxation in response to 17á-estradiol by isolated perfused hearts from intact normotensive male and female rats as well as the contribution of endothelium and its relaxing factors to this action. Baseline coronary perfusion pressure was determined and the vasoactive effects of 17á-estradiol (10 µM) were assessed by in bolus administration before and after endothelium denudation by infusion of 0.25 µM sodium deoxycholate or perfusion with 100 µM L-NAME, 2.8 µM indomethacin, 0.75 µM clotrimazole, 100 µM L-NAME plus 2.8 µM indomethacin, and 100 µM L-NAME plus 0.75 µM clotrimazole. Baseline coronary perfusion pressure differed significantly between males (84 ± 2 mmHg, N = 61) and females (102 ± 2 mmHg, N = 61). Bolus injection of 10 µM 17á-estradiol elicited a transient relaxing response in all groups, which was greater in coronary beds from females. For both sexes, the relaxing response to 17á-estradiol was at least in part endothelium-dependent. In the presence of the nitric oxide synthase inhibitor L-NAME, the relaxing response to 17á-estradiol was reduced only in females. Nevertheless, in the presence of indomethacin, a cyclooxygenase inhibitor, or clotrimazole, a cytochrome P450 inhibitor, the 17á-estradiol response was significantly reduced in both groups. In addition, combined treatment with L-NAME plus indomethacin or L-NAME plus clotrimazole also reduced the 17á-estradiol response in both groups. These results indicate the importance of prostacyclin and endothelium-derived hyperpolarizing factor in the relaxing response to 17á-estradiol. 17á-estradiol-induced relaxation may play an important role in the regulation of coronary tone and this may be one of the reasons why estrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women.

Oral administration of L-arginine decreases blood pressure and increases renal excretion of sodium and water in renovascular hypertensive rats

The two-kidney, one-clip renovascular (2K1C) hypertension model is characterized by a reduction in renal flow on the clipped artery that activates the renin-angiotensin system. Endothelium dysfunction, including diminished nitric oxide production, is also believed to play a role in the pathophysiology of this model. Some studies have shown an effect of L-arginine (L-Arg, a nitric oxide precursor) on hypertension. In the present study we determined the ability of L-Arg (7 days of treatment) to reduce blood pressure and alter renal excretions of water, Na+ and K+ in a model of 2K1C-induced hypertension. Under ether anesthesia, male Wistar rats (150-170 g) had a silver clip (0.20 mm) placed around the left renal artery to produce the 2K1C renovascular hypertension model. In the experimental group, the drinking water was replaced with an L-Arg solution (10 mg/ml; average intake of 300 mg/day) from the 7th to the 14th day after surgery. Sham-operated rats were used as controls. At the end of the treatment period, mean blood pressure was measured in conscious animals. The animals were then killed and the kidneys were removed and weighed. There was a significant reduction of mean blood pressure in the L-Arg-treated group when compared to control (129 ± 7 vs 168 ± 6 mmHg, N = 8-10 per group; P<0.05). Concomitantly, a significant enhancement of water and Na+ excretion was observed in the 2K1C L-Arg-treated group when compared to control (water: 13.0 ± 0.7 vs 9.2 ± 0.5 ml/day, P<0.01; Na+: 1.1 ± 0.05 vs 0.8 ± 0.05 mEq/day, respectively, P<0.01). These results show that orally administered L-Arg acts on the kidney, possibly inducing changes in renal hemodynamics or tubular transport due to an increase in nitric oxide formation

The cardiopulmonary reflexes of spontaneously hypertensive rats are normalized after regression of left ventricular hypertrophy and hypertension

Cardiopulmonary reflexes are activated via changes in cardiac filling pressure (volume-sensitive reflex) and chemical stimulation (chemosensitive reflex). The sensitivity of the cardiopulmonary reflexes to these stimuli is impaired in the spontaneously hypertensive rat (SHR) and other models of hypertension and is thought to be associated with cardiac hypertrophy. The present study investigated whether the sensitivity of the cardiopulmonary reflexes in SHR is restored when cardiac hypertrophy and hypertension are reduced by enalapril treatment. Untreated SHR and WKY rats were fed a normal diet. Another groups of rats were treated with enalapril (10 mg kg-1 day-1, mixed in the diet; SHRE or WKYE) for one month. After treatment, the volume-sensitive reflex was evaluated in each group by determining the decrease in magnitude of the efferent renal sympathetic nerve activity (RSNA) produced by acute isotonic saline volume expansion. Chemoreflex sensitivity was evaluated by examining the bradycardia response elicited by phenyldiguanide administration. Cardiac hypertrophy was determined from the left ventricular/body weight (LV/BW) ratio. Volume expansion produced an attenuated renal sympathoinhibitory response in SHR as compared to WKY rats. As compared to the levels observed in normotensive WKY rats, however, enalapril treatment restored the volume expansion-induced decrease in RSNA in SHRE. SHR with established hypertension had a higher LV/BW ratio (45 percent) as compared to normotensive WKY rats. With enalapril treatment, the LV/BW ratio was reduced to 19 percent in SHRE. Finally, the reflex-induced bradycardia response produced by phenyldiguanide was significantly attenuated in SHR compared to WKY rats. Unlike the effects on the volume reflex, the sensitivity of the cardiac chemosensitive reflex to phenyldiguanide was not restored by enalapril treatment in SHRE. Taken together, these results indicate that the impairment of the volume-sensitive, but not the chemosensitive, reflex can be restored by treatment of SHR with enalapril. It is possible that by augmenting the gain of the volume-sensitive reflex control of RSNA, enalapril contributed to the reversal of cardiac hypertrophy and normalization of arterial blood pressure in SHR.

The Na+Ca2+ exchange mechanism as a regulator of post rest contractions in cardiac muscle

The effects of external Na+ concentration and stimulation rate changes on the post rest contraction of rat myocardium were studied. An increase in external Na+ concentration or in stimulation rate causes relative potentiation of the post rest contractions, suggesting that the sarcolemmal Na+-Ca2+ exchange mechanism affects the mafgnitude of the potentiation of post rest contractions