In this study, we investigated some mechanisms involved in sodium-dependent hypertension of rats exposed to chronic salt (NaCl) intake from weaning until adult age. Weaned male Wistar rats were placed under high (0.90% w/w, HS) or regular (0.27% w/w, Cont) sodium diets for 12 weeks. Water consumption, urine output and sodium excretion were higher in HS rats compared to control. Blood pressure (BP) was directly measured by the arterial catheter and found 13.8% higher in HS vs Cont rats. Ganglionic blockade with hexamethonium caused greater fall in the BP of HS rats (33%), and central antagonism of AT1 receptors (losartan) microinjected into the lateral ventricle reduced BP level of HS, but not of Cont group. Heart rate variability analysis revealed sympathetic prevalence on modulation of the systolic interval. HS diet did not affect creatinine clearance. Kidney histological analysis revealed no significant change in renal corpuscle structure. Sodium and potassium concentrations in CSF were found higher in HS rats despite no change in plasma concentration of these ions. Taken together, data suggest that animals exposed to chronic salt intake to a level close to that reported for human’ diet since weaning lead to hypertension, which appears to rely on sodium-driven neurogenic mechanisms.

High sodium intake is an important factor associated with hypertension. High-sodium intake with exercise training can modify homeostatic hydro-electrolytic balance, but the effects of this association are mostly unknown. In this study, we sought to investigate the effects of swimming training (ST) on cerebrospinal fluid (CSF) Na + concentration, sympathetic drive, blood pressure (BP) and renal function of rats fed a 0.9% Na + (equivalent to 2% NaCl) diet with free access to water for 22 weeks after weaning. Male Wistar rats were assigned to two cohorts: (1) fed standard diet (SD) and (2) fed high-sodium (HS) diet. Each cohort was further divided into trained and sedentary groups. ST normalised BP levels of HS rats as well as the higher sympathetically related pressor activity assessed by pharmacological blockade of ganglionic transmission (hexamethonium). ST preserved the renal function and attenuated the glomerular shrinkage elicited by HS. No change in blood volume was found among the groups. CSF [Na + ] levels were higher in sedentary HS rats but were reduced by ST. Our findings showed that ST effectively normalised BP of HS rats, independent of its effects on hydro-electrolytic balance, which might involve neurogenic mechanisms regulated by Na + levels in the CSF as well as renal protection.

Redox imbalance in regions of the CNS controlling blood pressure is increasingly recognized as a leading factor for hypertension. Nucleus tractus solitarius (NTS) of the dorsomedial medulla is the main region receiving excitatory visceral sensory inputs that modulate autonomic efferent drive to the cardiovascular system. This study sought to determine the capacity of reduced glutathione, a major bioactive antioxidant, to modulate NTS-mediated control of cardiovascular function in unanaesthetized rats. Male Fischer 344 rats were used for microinjection experiments. Cardiovascular responses to L-glutamate were first used to verify accurate placement of injections into the dorsomedial region comprising the NTS. Next, responses to GSH or vehicle were recorded followed by responses to L-glutamate again at the same site. GSH microinjection increased mean arterial pressure (MAP) compared to vehicle and abrogated responses to subsequent injection of L-glutamate. These data indicate that GSH microinjection into the NTS affects blood pressure regulation by dorsomedial neuronal circuits and blunts L-glutamate driven excitation in this region. These findings raise the possibility that increased antioxidant actions of GSH in NTS could contribute to autonomic control dysfunctions of the cardiovascular system.

No abstract

Edited by: Jian Wang New Findings r What is the central question of this study?In this study, we sought to investigate whether cardiovascular responses to peripheral chemoreflex activation of rats recovered from protein restriction are related to activation of AT 1 receptors. r What is the main finding and its importance?This study highlights the fact that angiotensinergic mechanisms activated by AT 1 receptors do not support increased responses to peripheral chemoreflex activation by KCN in rats recovered from protein restriction. Also, we found that protein restriction led to increased resting ventilation in adult rats, even after recovery.The effects of a low-protein diet followed by recovery on cardiorespiratory responses to peripheral chemoreflex activation were tested before and after systemic angiotensin II type 1 (AT 1 ) receptor antagonism. Male Fischer rats were divided into control and recovered (R-PR) groups after weaning. The R-PR rats were fed a low-protein (8%) diet for 35 days and recovered with a normal protein (20%) diet for 70 days. Control rats received a normal protein diet for 105 days (CG 105 ). After cannulation surgery, mean arterial pressure, heart rate, respiratory frequency, tidal volume and minute ventilation were acquired using a digital recording system in freely moving rats. The role of angintensin II was evaluated by systemic antagonism of AT 1 receptors with losartan (20 mg kg −1 i.v.). The peripheral chemoreflex was elicited by increasing doses of KCN (20-160 μg kg min −1 , i.v.). At baseline, R-PR rats presented increased heart rate and minute ventilation (372 ± 34 beats min −1 and 1.274 ± 377 ml kg −1 min −1 ) compared with CG 105 animals (332 ± 22 beats min −1 and 856 ± 112 ml kg −1 min −1 ). Mean arterial pressure was not different between the groups. Pressor and bradycardic responses evoked by KCN (60 μg kg −1 ) were increased in R-PR (+45 ± 13 mmHg and −77 ± 47 beats min −1 ) compared with CG 105 rats (+25 ± 17 mmHg and −27 ± 28 beats min −1 ), but no difference was found in the tachypnoeic response. These differences were preserved after losartan. The data suggest that angiotensin II acting on AT 1 receptors may not be associated with the increased heart rate, increased minute

New Findings What is the central question of this study? Is the cardiovascular phenotype of high blood pressure observed in rats salt loaded with 2% NaCl in drinking solution a blood volume‐dependent hypertension? What is the main finding and its importance? Animals exposed to 2% NaCl drinking solution develop hypertension, with dominance of sympathetic outflow and high [Na+] in the cerebrospinal fluid, but without changes in the blood volume. The phenotype of salt‐dependent hypertension might be related to accumulation of [Na+] in the cerebrospinal fluid, which makes it an interesting animal model in which to study the neuronal pathways involved in control of the circulation in osmotic challenge conditions. Abstract Evidence suggests that hypertension induced by high salt intake is correlated with an autonomic imbalance that favours sympathetic hyperactivity and an increase in vascular resistance, indicating a neurogenic component to this pathology. Although there are several animal models in which to study salt‐induced hypertension with prolonged exposure to a high‐sodium diet, here we sought to investigate whether the increase in arterial blood pressure of rats subjected to a short exposure to high salt, with 2% NaCl drinking solution instead of water, relies on changes in the circulating blood volume. Male Wistar rats were divided randomly into three groups: euhydrated (EU, n = 10), salt loaded (SL, n = 13) and water deprived (WD, n = 6). The SL rats exhibited a significant increase in mean arterial blood pressure, with a large low‐frequency component of systolic arterial blood pressure variability, when compared with the EU group. Circulating blood volume did not differ between SL and EU rats, but it was lower in WD rats. Compared with EU rats, the [Na+] in cerebrospinal fluid was higher in SL rats and similar in magnitude to the WD rats. Plasma [Na+] did not differ between SL and EU rats, but it was higher in WD rats. Collectively, our data suggest that the hypertension induced by a short exposure to high salt intake closely resembles a neurogenic mechanism, but not a blood volume‐dependent mechanism, with cumulative [Na+] in the cerebrospinal fluid that could be associated with changes in the neurochemistry of autonomic nuclei, which are highly susceptible to osmotic stress related to high salt consumption.

No abstract