Thyroid hormone disorder and the heart: The role of cardiolipin in calcium handling.

New Findings: What is the central question of this study? Do alterations in thyroid status affect haemodynamic parameters and echocardiographic measurements in the rat postnatal heart, and calcium handling, contractility, relaxation and cardiolipin content in isolated rat cardiomyocytes? What is the main finding and its importance? An imbalance in phospholipids of the mitochondrial membrane such as cardiolipin is related to defects in mitochondrial function. T -dependent cardiolipin signals contribute to the maintenance of mitochondrial homeostasis and involve Ca handling, this pathway being more important in hypothyroidism.

Abstract: The objective of this study was to evaluate whether alterations in thyroid status affect (1) haemodynamic parameters and echocardiographic measurements in the rat postnatal heart, and (2) calcium handling, contractility, relaxation and cardiolipin content in isolated rat cardiomyocytes.

Cardiotoxic Effects of the Antineoplastic Doxorubicin in a Model of Metabolic Syndrome: Oxidative Stress and Transporter Expression in the Heart.

The aim of the present work was to examine whether metabolic syndrome-like conditions in rats with fructose (F) overload modify the cardiotoxic effects induced by doxorubicin (DOX) and whether the treatment altered the expression of P-gp, breast cancer resistance protein, and organic cation/carnitine transporters in the heart. Male Sprague-Dawley rats received either tap water (control group [C]; n = 16) or water with F 10% wt/vol (n = 16) during 8 weeks. Three days before being killed, the animals received a single dose of DOX (6 mg/kg, ip, md) (C-DOX and F-DOX groups) or vehicle (VEH; ISS 1 mL/kg BW; ip) (C-VEH and F-VEH groups) (n = 8 per group).

EPO and EPO-Receptor System as Potential Actionable Mechanism for the Protection of Brain and Heart in Refractory Epilepsy and SUDEP.

The most important activity of erythropoietin (EPO) is the regulation of erythrocyte production by activation of the erythropoietin receptor (EPO-R), which triggers the activation of anti-apoptotic and proliferative responses of erythroid progenitor cells. Additionally, to erythropoietic EPO activity, an antiapoptotic effect has been described in a wide spectrum of tissues. EPO low levels are found in the central nervous system (CNS), while EPO-R is expressed in most CNS cell types.

Erythropoietin Improves Cardiovascular Function in Adult Rats After Acute Hemorrhage.

Erythropoietin (EPO) has been linked to cardioprotective effects. However, its effects during the aging process are little known. We investigated the effect of EPO administration on hemodynamic parameters, cardiac function, oxidative damage, and erythropoietin receptor (EPOR) expression pattern in the hypovolemic state.

Thyroid disorders and nitric oxide in cardiovascular adaptation to hypovolemia.

This study aimed to investigate whether nitric oxide participates in the cardiovascular function and haemodynamic adaptation to acute haemorrhage in animals with thyroid disorders. Sprague-Dawley rats aged 2months old treated with T3 (hyper, 20μg/100g body weight) or 0.02% methimazole (hypo, w/v) during 28days were pre-treated with N(G) nitro-l-arginine methyl ester (L-NAME) and submitted to 20% blood loss.

Effects of nitric oxide system and osmotic stress on Aquaporin-1 in the postnatal heart.

Aquaporin-1 (AQP1) is expressed in the heart and its relationship with NO system has not been fully explored. The aims of this work were to study the effects of NO system inhibition on AQP1 abundance and localization and evaluate AQP1 S-nitrosylation in a model of water restriction during postnatal growth. Rats aged 25 and 50days (n=15) were divided in: R: water restriction; C: water ad libitum; RL: L-NAME (4mg/kgday)+water restriction; CL: L-NAME+water ad libitum.

Neonatal hyperthyroidism on rat heart: interrelation with nitric oxide and sex.

Purpose: To clarify the mechanism mediating the effect of hyperthyroidism on cardiac function during the second month of life in rats.

Methods: Male and female Sprague-Dawley rats were assigned to a control or to a triiodothyronine (T3)-treated group. Treatment of each group was started on the third day after birth.

Involvement of nitric oxide and caveolins in the age-associated functional and structural changes in a heart under osmotic stress.

Previous work done in our laboratory showed that water restriction during 24 and 72h induced changes in cardiovascular NOS activity without altering NOS protein levels in young and adult animals. These findings indicate that the involvement of NO in the regulatory mechanisms during dehydration depends on the magnitude of the water restriction and on age. Our aim was to study whether a controlled water restriction of 1 month affects cardiac function, NO synthase (NOS) activity and NOS, and cav-1 and -3 protein levels in rats during aging.

Dehydration affects cardiovascular nitric oxide synthases and caveolins in growing rats.

Purpose: During the postnatal stage, cardiovascular nitric oxide (NO) system and caveolins (cav) may be regulated differentially in response to hypovolemic state induced by water restriction. Our aim was to examine the effects of water restriction on NO synthases (NOS) and cav in the atria, ventricle and aorta of growing rats.

Methods: Male Sprague-Dawley rats aged 25 and 50 days were divided into (n = 15): WR: water restriction 3 days; WAL: water ad libitum 3 days.

Role of angiotensin II and oxidative stress on renal aquaporins expression in hypernatremic rats.

The aim of this study was to assess whether endogenous Ang II and oxidative stress produced by acute hypertonic sodium overload may regulate the expression of aquaporin-1 (AQP-1) and aquaporin-2 (AQP-2) in the kidney. Groups of anesthetized male Sprague-Dawley rats were infused with isotonic saline solution (control) or with hypertonic saline solution (Na group, 1 M NaCl), either alone or with losartan (10 mg kg(-1)) or tempol (0.5 mg min(-1) kg(-1)) during 2 h.

Nitric oxide and AQP2 in hypothyroid rats: a link between aging and water homeostasis.

Objective: Hypothyroid state and aging are associated with impairment in water reabsorption and changes in aquaporin water channel type 2 (AQP2). Nitric oxide (NO) is involved in AQP2 trafficking to the apical plasma membrane in medullary collecting duct cells. The purpose of this study was to investigate whether aging and hypothyroidism alter renal function, and whether medullary NO and AQP2 are implicated in maintaining water homeostasis.

Comparison of cardiovascular aquaporin-1 changes during water restriction between 25- and 50-day-old rats.

Purpose: Aquaporin-1 (AQP1) is the predominant water channel in the heart, linked to cardiovascular homeostasis. Our aim was to study cardiovascular AQP1 distribution and protein levels during osmotic stress and subsequent hydration during postnatal growth.

Methods: Rats aged 25 and 50 days were divided in: 3d-WR: water restriction 3 days; 3d-WAL: water ad libitum 3 days; 6d-WR+ORS: water restriction 3 days + oral rehydration solution (ORS) 3 days; and 6d-WAL: water ad libitum 6 days.

Contribution of caveolin-1 to ventricular nitric oxide in age-related adaptation to hypovolemic state.

Our previous results have shown that hypovolemic state induced by acute hemorrhage in young anesthetized rats triggers heterogeneous and dynamic nitric oxide synthase (NOS) activation, modulating the cardiovascular response. Involvement of the nitric oxide pathway is both isoform-specific and time-dependent. The aim of the present study was to investigate changes in activity and protein levels of the different NOS forms, changes in the abundance of caveolin-1 during hypovolemic state and caveolin-1/eNOS association using young and middle-aged rats.

Salt-induced downregulation of renal aquaporins is prevented by losartan.

Aims: The purpose of this study was to investigate the expression of aquaporin-1 (AQP-1) and aquaporin-2 (AQP-2) in the renal tubule of rats fed with a high-salt diet and its modulation by the AT1 receptor blocker losartan.

Main Methods: The experiments were performed in four groups of rats fed for 3 weeks with the following diets: regular rat chow (NS); high-salt (8% NaCl) chow (HS), NS plus losartan (NS-L) and HS plus losartan (HS-L). Losartan (40 mg x kg(-1)) was administered in the drinking water.

Hypothyroidism: age-related influence on cardiovascular nitric oxide system in rats.

This study investigates whether changes in nitric oxide (NO) production participate in the cardiovascular manifestations of hypothyroidism and whether these changes are age-related. Sprague-Dawley rats aged 2 and 18 months old were treated with 0.02% methimazole (wt/vol) during 28 days.

Diastolic function during hemorrhagic shock in rabbits.

Hemorrhage (H) is associated with a left ventricular (LV) dysfunction. However, the diastolic function has not been studied in detail. The main goal was to assess the diastolic function both during and 120 min after bleeding, in the absence and in the presence of L-NAME.

Hypovolemic state: age-related influence of water restriction on cardiac nitric oxide synthase in rats.

Aim Of Study: We have assessed the influence of water restriction stress on the nitric oxide (NO) synthase in heart and aorta tissues in young 2-month-old and middle-aged 12-month-old rats.

Methods: Animals were divided into control and 24- and 72-h water-deprived groups. We evaluated systolic blood pressure (SBP), biochemical parameters, nitrate and nitrite urinary excretion (UNOx), NADPH-diaphorase activity, and protein levels of NOS in the right atria, left ventricle, and thoracic aorta tissues.

Exposure to zinc deficiency in fetal and postnatal life determines nitric oxide system activity and arterial blood pressure levels in adult rats.

We had previously shown that prenatal exposure to Zn-deficient diets induces an increase in blood pressure and impairs renal function in adult rats. The aim of the present study was to investigate if moderate Zn restriction during early growth periods, fetal life and lactation would induce impairment in the vascular and renal NO system and alterations in plasma lipid profile. We also investigated if these effects persisted into adult life, even when a Zn-replete diet was provided after weaning.

Moderate zinc restriction during fetal and postnatal growth of rats: effects on adult arterial blood pressure and kidney.

Intrauterine and postnatal zinc restriction may result in an adverse environment for the development of cardiovascular and renal systems. This study evaluated the effects of moderate zinc deficiency during fetal life, lactation, and/or postweaning growth on systolic blood pressure, renal function, and morphology in adult life. Female Wistar rats received low (8 ppm) or control (30 ppm) zinc diets from the beginning of pregnancy up to weaning.

Hypovolemic state: involvement of nitric oxide in the aged related alterations of aquaporins-2 abundance in rat kidney.

Aim: To examine the effect of nitric oxide (NO) on the expression and/or localization of inner medulla collecting duct aquaporin-2 water channel (AQP2) in young and adult hemorrhaged anesthetized rats.

Methods: Rats of 2 (young) and 12 mo (adult) old (n=15) were divided into: Sham animals with and without NG-nitro-l-arginine methyl ester (L-NAME) treatment (S L-NAME and S); hemorrhaged animals (20% blood loss) with and without L-NAME (H L-NAME and H). Mean arterial pressure (MAP) was continuously monitored and AQP2 expression and inmunolocalization were evaluated at 120 min after bleeding.

Cardiac mitochondrial nitric oxide: a regulator of heart rate?

Alterations in autonomic control and myocardial nitric-oxide (NO) production are likely linked to the development and progression of heart dysfunction. By focusing on heart rate, the complexity of the actions of NO at distinct levels throughout the autonomic nervous system and its relationship with other regulators can be demonstrated. Given the multiple and opposing actions of NO on cardiac control, it is difficult to interpret a response after a global intervention in the NO system.

Amiloride-sensitive and amiloride-insensitive kaliuresis in advanced chronic kidney disease.

Background: Salt delivery to the distal nephron and sodium reabsorption in this segment are considered critical factors that modulate kaliuresis in chronic kidney disease (CKD). Amiloride, a drug that blocks Na(+) reabsorption in the distal nephron, can help to assess the role of Na+ transport in this segment on the kaliuresis of CKD patients.

Methods: A bolus of amiloride (1 mg/kg body weight) followed by an intravenous infusion (1 mg/kg body weight per hour) was administered to 6 normal subjects and 10 patients with CKD undergoing water diuresis.

Zinc deficiency during growth: influence on renal function and morphology.

This study was designed to investigate the effects of moderate zinc deficiency during growth on renal morphology and function in adult life. Weaned male Wistar rats were divided into two groups and fed either a moderately zinc-deficient diet (zinc: 8 mg/kg, n=12) or a control diet (zinc: 30 mg/kg, n=12) for 60 days. We evaluated: renal parameters, NADPH-diaphorase and nitric oxide synthase activity in kidney, renal morphology and apoptotic cells in renal cortex.

Role of NPR-C natriuretic receptor in nitric oxide system activation induced by atrial natriuretic peptide.

Atrial natriuretic peptide (ANP) exerts its hypotensive, natriuretic and diuretic effects, almost in part, through the activation of nitric oxide synthase (NOS). The aim was to investigate the natriuretic receptor type and the signaling cascade involved in NOS activation induced by ANP. Male Wistar rats were sacrificed and NOS activity was determined in kidney, aorta and heart with L-[U14C]-arginine, as substrate.

Nitric oxide synthases are involved in the modulation of cardiovascular adaptation in hemorrhaged rats.

Aim: Nitric oxide has been implicated in the cardiovascular adaptation to hemorrhagic shock. Our aim was to study the potential role of nitric oxide synthases (NOS) in the cardiovascular response in hemorrhagic hypotension produced experimentally in anesthetized rats.

Methods: Groups of animals (n = 14, per group): (a) normotensive; (b) hypovolemic (20% blood loss); (c) normotensive and pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME); (d) hypovolemic and pretreatment with L-NAME.