O envolvimento do núcleo paraventricular do hipotálamo na manutenção da pressão arterial e modulação do tônus simpático renal de ratos tratados com dieta rica em sódio na fase pós natal
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2019-06-28
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Universidade Federal de Goiás
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High sodium intake can affect the excitability of neurons in regions responsible for the control of sympathetic nervous activity. It is known that the neuronal activity of the hypothalamus paraventricular nucleus (PVN) is increased in several models of sodium-sensitive arterial hypertension (SSH). Diseases that develop in adulthood are related to certain exposures suffered by the individual during the early stages of life. However, the literature point out differences between males and females in the expression of hypertension in both animal and human models, and in females, estrogen sometimes has a cardioprotective effect. In the present study, we investigated whether changes in diet during the postnatal phases contribute to central alterations in the control of renal sympathetic tone in males and females, and whether they persist in adulthood. More specifically, we evaluated the contribution of the PVN in the control of cardiovascular parameters and sympathetic nervous activity (SNA) after treatment with a sodium-rich diet for 30 days in adult rats and rats. Twenty one days old wistar male and female rats were divided into two groups: control group, composed of males (MCTRL) and females (FCTRL), maintained with water; and experimental group, composed of males (MEXP) and females (FEXP), maintained with hypertonic solution of 0.3 M NaCl. Animals of all groups received chow and hypertonic solution or water ad libitum for 30 days. After treatment, the animals of all groups were maintained with water and chow for 15 days (recovery period). Daily food and fluid (0.3 M NaCl or water) intake and body weight were monitored during the treatment and recovery periods. At the end of treatment, the treated male rats were found to have lower body weight compared to controls (MEXP (n = 9): 115.3 ± 4.7 g vs. MCTRL (n = 9): 168.0 ± 8.0 g, p <0.05). However, this difference was not observed between the experimental and control female groups (FEXP (n = 8): 119.5 ± 5.3 g vs. FCTRL (n = 8): 134.1 ± 5.2 g). We also observed that the experimental animals ingested a greater amount of fluid per gram of body weight (bw) than control animals MEXP (n=9): 0.717 ± 0.120 mL/g/bw vs. MCTRL (n=9): 0.209; FEXP (n=8): 0.576 ± 0.060 mL/g/bw vs. FCTRL (n=8): 0.251 ± 0.011 mL/g/bw, p < 0.05) and we observed a decrease in the excreted volume (Vexc) in experimental females compared to the ingested volume (Ving) (FEXP (n=8): Ving 89.6 ± 5.6 mL vs. Vexc 56.8 ± 5.2 mL, p < 0.05). In the recovery period there was no difference in daily water intake between groups (MEXP (n=9): 0.203 ± 0.008 mL/g/bw vs. MCTRL (n=9): 0,171 ± 0.005 mL/g/bw; FEXP (n=8): 0,229 ± 0,013 mL/g/bw vs. FCTRL (n=8): 0.187 ± 0,010 mL/g/bw). In another set of experiments, we evaluated the participation of the PVN in the maintenance of sympathetic tonus after treatment with a high sodium diet for 30 days. Bilateral nanoinjections of 50 nL of muscimol (GABAA agonist, 4 mM) were performed in the PVN in experimental and control animals during recording of mean arterial pressure (MAP), heart rate (HR) and renal SNA (RSNA). It is noteworthy that in the females these experiments were performed in the diestrus of the estrous cycle. In the anaesthetized experiments, the males of the treated group showed higher values of baseline MAP compared to both control male group and to female groups (PAM: MEXP (n=6): 108.2 ± 2.9 mmHg vs. MCTRL (n=6): 92 ± 5.4 mmHg vs. FEXP (n=6): 102.7 ± 4.4 mmHg vs. FCTRL (n=6): 90.8 ± 1.8 mmHg, p<0.05). Inhibition of the PVN promoted a reduction on MAP of experimental groups when compared to control groups: (Δ MAP: MEXP (n=6): -14.9 ± 1.5 mmHg vs. MCTRL (n=6): -7.2 ± 0.7 mmHg vs. FEXP (n=6): -12.9 ± 1.7 mmHg vs. FCTRL (n=6): -4.8 ± 0.6 mmHg, p <0.05). On the other hand, no differences were observed in the HR responses of the evaluated groups (Δ HR: MEXP (n=6): -35.8 ± 6.6 bpm vs. MCTRL (n=6): -21.6 ± 2.9 bpm vs. FEXP (n=6): -27.8 ± 3.5 bpm vs. FCTRL (n=6): -31.0 ± 4.4 bpm). In addition, acute inhibition of PVN promoted renal sympathoinhibition in experimental animals compared to controls (Δ % ANSR: MEXP (n=6): -17.3 ± 1.5% vs. MCTRL (n=6): -6.8 ± 1.0% vs. FEXP (n=6): -18.1 ± 0.5% vs. FCTRL (n=6): -3.0 ± 0.6%, p <0.05). The results demonstrated in the present study showed that the hypersodiuc diet during the early stages of life altered baseline MAP of experimental males. Additionally, we observed that the acute inhibition of PVN promoted cardiovascular and sympathetic changes in rats treated with a high sodium diet in comparison to the control group. Taken together, the observed results add new information to the literature and suggest that cardiovascular and sympathetic control regions, such as the PVN, may be more involved in the tonic modulation of blood pressure and RSNA in response to sodium overload in the postnatal phase of normotensive rats. Finally, our study points to the possibility that estrogen may have helped decrease the high blood pressure promoted by prolonged increase in sodium intake, but it was not enough to prevent the increase in the modulation of the sympathetic tone exerted by the PVN. However, future studies are needed to investigate pathways and mechanisms involved in these responses.
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ALMEIDA, M. T. O envolvimento do núcleo paraventricular do hipotálamo na manutenção da pressão arterial e modulação do tônus simpático renal de ratos tratados com dieta rica em sódio na fase pós natal. 2019. 73 f. Dissertação (Mestrado Ciências Fisiológicas) - Universidade Federal de Goiás, Goiânia, 2019.