Frequency-coded patterns of sympathetic vasomotor activity are differentially evoked by the paraventricular nucleus of the hypothalamus in the Goldblatt hypertension model

Abstract

The activation of specific brain areas involved in regulating the vasomotor sympathetic activity can lead to distinct effects in the postganglionic nerves in both physiological and pathological conditions, suggesting that the sympathetic vasomotor activity is differentially coded depending on the nerve outflow and the target organs. Previous studies investigating such patterns have mostly focused on the global energy of the signal. However, recent evidence has suggested that relevant information is coded in the power distribution along the frequency range. Disturbing the sympathoexcitatory vasomotor tone in the paraventricular nucleus of the hypothalamus (PVN) allows to investigate the sympathetic nerve activity in overloaded conditions in both hypertensive and control animals. By disinhibiting the PVN through the microinjection of bicuculline, an antagonist of {gamma}-aminobutyric acid type A (GABAa) receptors, in the Goldblatt (2K1C) rat model of hypertension we addressed the territorially differential changes in the frequency parameters of the renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively). We also tested the effect of the systemic administration of losartan, an antagonist of the angiotensin II type 1 receptors (AT1), in the attenuation of the increased rSNA and sSNA in 2K1C rats, once these changes are reported to be dependent on the AT1 activation in the Goldblatt model. Our results revealed that each nerve activity presents its own electrophysiological pattern of frequency-coded rhythm in each group, in basal condition and after bicuculline microinjection, but with no significant differences regarding total power comparison among groups. Additionally, the 2K1C animals treated with losartan showed no decrease in the hypertensive response triggered by the GABAa antagonism when compared to the non-treated 2K1C group. However, their spectral patterns of sympathetic nerve activity were different from the other two groups, suggesting that the systemic blockade of AT1 receptors does not totally recover the basal levels of neither the autonomic symptoms nor the electrophysiological patterns in the Goldblatt model, but act on their spectral frequency distribution. These results suggest that the differential responses evoked by the PVN were preferentially coded in frequency of vasomotor sympathetic responses, indicating that the PVN distinctly modulated each rhythmic activity. Financial Support - FAPESP (2019/25295-0)