Increased activity of the renin–angiotensin and sympathetic nervous systems is required for regulation of the blood pressure in rats fed a low‐protein diet

Abstract

New Findings r What is the central question of this study?Is the increase in blood pressure observed in rats fed a low protein diet due to overactivation of sympathetic and renin angiontensin systems? r What is the main finding and its importance?The data show an increase in the expression of angiotensin II type 1 receptors and an incrased sympathetic activity in this experimental model, suggesting that both systems are contributing to the high blood pressure observed in these animals.Previous studies have shown that postweaning protein restriction induces changes in the sympathetic nervous system in rats, leading to alterations in cardiovascular parameters. In addition, the renin-angiotensin system is also affected in these animals. Here, we hypothesized that adjustments in the interaction between the RAS and SNS underlie the cardiovascular adaptations observed in rats fed a low-protein diet. Thus, we evaluated the alterations in the mean arterial pressure (MAP) and heart rate of Fisher rats fed a protein-deficient diet before and after systemic administration of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II (Ang II) type 1 (AT 1 ) receptor antagonist losartan alone or in combination with the α 1 -adrenergic receptor antagonist prazosin. Administration of enalapril or losartan decreased the MAP only of rats under protein restriction. Prazosin injection after the infusion of losartan caused a further decrease in the MAP of malnourished rats. In contrast, only the administration of prazosin elicited a reduction in the MAP of control animals. When the sequence of administration of the antagonists was inverted, infusion of prazosin in animals fed the standard or the low-protein diet induced a reduction in the MAP that was further decreased by the subsequent injection of losartan. Importantly, in both protocols the responses of malnourished animals to losartan were markedly greater when compared with the control group. Moreover, these animals presented lower levels of circulating Ang II and a reduced responsiveness to Ang II. In contrast, the expression of AT 1 receptors in the aorta of malnourished animals was increased. Thus, our data suggest that the renin-angiotensin system is an important factor supporting

Increased α1-adrenoreceptor activity is required to sustain blood pressure in female rats under food restriction

“…These results indicate an increased α1-adrenergic receptor activity in these animals, with only 14 days of food restriction, which would be necessary to sustain the blood pressure. Importantly, animals fed a low protein diet, for 35 days, present a higher vasomotor tone that could be due to an increased sympathetic efferent activity [16,40], corroborating the idea that dietary restrictions can lead to increased SNS activation to the arteries. The pronounced tachycardic response in these animals could be, possibly, the result of the pronounced hypotension, which would activate the baroreflex circuit leading to a marked activation of the SNS to the heart.…”

“…The analogical signal from the amplifier was digitized by a 12 bit analogical-to-digital converter (PowerLab/400, ADI Instruments, Australia), and the pulsatile arterial pressure recorded at 1000 Hz by the software Chart 7.0 for Windows (ADInstruments, Australia). MAP and HR were derived on-line from the pulsatile arterial pressure using pulse-to-pulse analysis [16].…”

Maternal Protein Restriction Increases Respiratory and Sympathetic Activities and Sensitizes Peripheral Chemoreflex in Male Rat Offspring

“…Recent experimental and clinical evidence indicates that dysfunction of carotid body chemoreceptors plays a critical role in the progression of cardiorespiratory morbidities associated with baseline sympathetic overactivity, including sleep disorders, congestive heart failure, chronic pulmonary obstructive disease, and hypertension (9,12,13,27,(46)(47)(48). In agreement with this notion, we hypothesize that the enhanced baseline sympathetic and inspiratory motor activities of juvenile offspring from dams subjected to protein restriction during pregnancy and lactation, before the development of hypertension, are dependent, at least in part, on the sensitization of the peripheral chemoreflex.…”

“…The offspring of rat dams subjected to a maternal low-protein (LP) 10 diet is a model that is often used to study the mechanisms of maternal undernutrition-related hypertension (6)(7)(8), which has been suggested to be associated with changes in the functioning of the sympathetic nervous system (9,10). However, there is no direct evidence demonstrating that sympathetic vasoconstrictor tonus is elevated in rats subjected to a perinatal LP diet.…”

Changes in cardiovascular responses to chemoreflex activation of rats recovered from protein restriction are not related to AT1 receptors

“…Earlier studies involving protein restriction have shown that many changes in autonomic and hormonal mechanisms controlling the cardiovascular system take place to keep blood pressure close to normal levels (Fyhrquist & Saijonmaa, ; Gomide et al . ; Rodrigues‐Barbosa et al . ).…”