Efeitos da sobrecarga ou restrição crônica de sal na dieta durante a gestação e amamentação em ratas Wistar e sua repercussão sobre a prole / Renin-angiotensin system function and blood pressure in adult rats after perinatal salt overload

Alguns estudos têm procurado avaliar os efeitos de variações no consumo de sal no período perinatal sobre o sistema cardiovascular da prole na idade adulta. No entanto, várias questões ainda estão em aberto e merecem estudos adicionais. Neste trabalho, o OBJETIVO foi estudar os efeitos da sobrecarga ou restrição crônica de sal na dieta de ratas Wistar, durante a gestação e amamentação, sobre o ganho de peso, a pressão arterial, a sensibilidade da pressão arterial ao sal (SENS), a atividade do sistema renina-angiotensina, o conteúdo renal de angiotensina II (AII) e a densidade glomerular da prole na idade adulta. Foram utilizadas fêmeas Wistar recém desmamadas divididas em 3 grupos: dieta hipo (HO - 0,15% NaCl - n=8), normo (NR - 1,27% NaCl - n=9) ou hipersódica (HR – 7,94% NaCl - n=8). A quantidade de dieta oferecida as ratas foi ajustada de forma a manter o peso semelhante entre os grupos. A fecundação ocorreu na 12a semana de idade. Após o parto, apenas 8 recém-nascidos (4 machos e 4 fêmeas) permaneceram com suas mães. Após o desmame, todos os animais da prole receberam apenas a dieta NR. O peso materno foi medido diariamente até a fecundação e semanalmente até uma semana após o parto. O peso da prole foi medido no dia do parto e semanalmente após o desmame. A PA caudal materna foi medida desde uma semana antes da fecundação até uma semana após o parto (PAc-M) e na prole entre a 8a e a 12a semana de idade (PAc-P). Ao completar 12 semanas de idade, a prole foi submetida a um teste de sensibilidade da pressão arterial ao sal (1 semana em dieta HO seguido por 1 semana em dieta HR ou vice-versa). A atividade de renina plasmática (ARP) foi medida ao final de cada semana do teste. O conteúdo renal de AII foi avaliado por imunohistoquímica e a densidade glomerular através de um método histológico apropriado para a contagem dos glomérulos. Durante a gestação, a PAc-M foi maior no grupo HR (p<0,05) comparado aos grupos HO e NR. Na prole: 1)...

To study the influence of high salt intake during pregnancy and lactation on body weight, blood pressure, and the function of the renin-angiotensin system in adult rats. METHODS AND RESULTS: Female Wistar rats received a low (0.15 NaCl), normal (1.30), or high (8% diet) salt diet. Mating occurred on the 12th week of age. From weaning, the offspring received normal salt diet. Weekly tail-cuff blood pressure and body weight measurements were performed during pregnancy and in the offspring (body weight since weaning and tail-cuff blood pressure between the 8th and the 12th week of age). Salt sensitivity of the blood pressure was evaluated and plasma renin activity determinations were performed in the 12-week-old offspring. Immunohistochemistry for renal angiotensin II was performed in the adult offspring. Renal mass and the number of glomeruli were determined. Tail-cuff blood pressure was higher in salt overloaded dams than in normal and low salt ones. In the adult offspring from the high salt dams, lower body weight, higher tail-cuff blood pressure, lower salt sensitivity in females, and increased kidney angiotensin II were observed. Plasma renin activity did not change with changes in salt intake in the adult offspring submitted to high salt environment during the perinatal period. In the offspring, renal mass and the number of glomeruli were not influenced by the dams' salt intake. CONCLUSIONS: Salt overload during pregnancy and/or lactation has long-term effects on offspring's body weight and blood pressure. In addition, high salt diet during the perinatal period induced renin-angiotensin system functional disturbances in the offspring.

Bi-directional actions of estrogen on the renin-angiotensin system

Estrogen stimulates the renin-angiotensin system by augmenting both tissue and circulating levels of angiotensinogen and renin. We show, however, that angiotensin converting enzyme (ACE) activity in the circulation and in tissues is reduced in two animal models of postmenopausal chronic hormone replacement. We observed a reduction of ACE activity in association with a significant increase in plasma angiotensin I (Ang I) and hyperreninemia in ovariectomized monkeys treated with Premarin (conjugated equine estrogen) replacement for 30 months. Plasma angiotensin II (Ang II) levels were not increased in monkeys treated with estrogen, suggesting that the decrease in ACE curtailed the formation of the peptide. The Ang II/Ang I ratio, an in vivo index of ACE activity, was significantly reduced by estrogen treatment, further supporting the biochemical significance of estrogen's inhibition of ACE. In ovariectomized transgenic hypertensive (mRen2)27 rats submitted to estrogen replacement treatment for 3 weeks, ACE activity in plasma and tissue (aorta and kidney) and circulating Ang II levels were reduced, whereas circulating levels of angiotensin-(1-7) (Ang-(1-7) were increased. Ang-(1-7), the N-terminal fragment of Ang II, is a novel vasodilator and antihypertensive peptide. Thus, the net balance of these effects of estrogen on the renin-angiotensin vasoconstrictor/vasodilator system is to promote the antihypertensive effect.

Angiotensin-1(1-7) is a potent antidiuretic peptide in rats

We have shown previously that angiotensin (1-7) (Asp-Arg Val-Tyr-Ile-His-Pro) is a biologically active endogenous angiotensin which is a major product of angiotensin I processing by an angiotensin converting enzyme (ACE)-independent pathway. Intense staining for angiotensin (1-7) immunoreactivity was demonstrable in brain areas related to the maintenance of hydromineral balance, suggesting the involvement of this peptide in this process. In the present study we investigated the antidiuretic effect of angiotensin (1-7), by determining its effect on the water diuresis produced by an ip water load (5 ml/100 g) in male Wistar rats. The peptide had a pronounced antidiuretic effect when administered peripherally in doses ranging from 5.5 to 22 pmol/100 g. In contrast, angiotensin - (1-7) and vasopressin (AVP) showed that both peptides act in the same molar range althouth AVP was slightly more potent than angiotensin (1-7). Urine volumes for 22 pmol/100 g angiotensin (1-7) were 0.85 ñ 0.26 and 3.47 ñ 0.36 ml for hours 1 and 2, respectively, whereas they were 0.54 ñ 0.40 and 2.38 ñ 0.64 ml for 10 pmol/100 g AVP. There was apparent additivity of effect when 10 pmol of each peptide were administered simultaneously (0.0 and 1.72 ñ 0.45 ml vs 2.58 ñ 0.45 and 3.85 ñ 0.35 ml for hours 1 and 2, respectively). The unexpected potency of this peptide in reducing water diuresis and its localization in brain areas related to AVP release suggest a role for angiotensin (1-7) in the mechanisms involved in the maintenance of hydroelectrolyte balance