Glutamate and GABA neurotransmission are increased in paraventricular nucleus of hypothalamus in rats induced to 6‐OHDA parkinsonism: Involvement of nNOS

Abstract

Aim: Parkinson's disease (PD) is a progressive neurodegenerative disease that manifests itself clinically after reaching an advanced pathological stage. Besides motor signals, PD patients present cardiovascular and autonomic alterations.Recent data showed that rats induced to Parkinsonism by 6-hydroxydopamine (6-OHDA) administration in the substantia nigra pars compacta (SNpc) showed lower mean arterial pressure (MAP) and heart rate (HR), as reduction in sympathetic modulation. The paraventricular nucleus of the hypothalamus (PVN) is an important site for autonomic and cardiovascular control, and amino acid neurotransmission has a central role. We evaluate PVN amino acid neurotransmission in cardiovascular and autonomic effects of 6-OHDA Parkinsonism. Methods: Male Wistar rats were submitted to guide cannulas implantation into the PVN. 6-OHDA or sterile saline (sham) was administered bilaterally in the SNpc. After 7 days, cardiovascular recordings in conscious state was performed. Results: Bicuculline promoted an increase in MAP and HR in sham group and exacerbated those effects in 6-OHDA group. NBQX (non-NMDA inhibitor) did not promote changes in sham as in 6-OHDA group. On the other hand, PVN microinjection of LY235959 (NMDA inhibitor) in sham group did not induced cardiovascular alterations, but decreased MAP and HR in 6-OHDA group. Compared to Sham group, 6-OHDA lesion increased the number of neuronal nitric oxide synthase (nNOS)-immunoreactive neurons in the PVN and, nNOS inhibition promoted higher increases in MAP and HR. Conclusion: Our data suggest that the decreased baseline blood pressure and heart rate in animals with Parkinsonism may be due to an increased GABAergic tone via nNOS in the PVN. K E Y W O R D Sarterial pressure, baroreflex, bicuculline, heart rate, heart rate variability, nitric oxide

Salusin-β in Intermediate Dorsal Motor Nucleus of the Vagus Regulates Sympathetic-Parasympathetic Balance and Blood Pressure

“…It is known that the PVN is a critical integrated center in control sympathetic outflow [ 33 ]. The receptors of γ-aminobutyric acid (GABA) in the PVN is involved in inhibiting in sympathetic outflow and blood pressure [ 34 , 35 ]. Thus, we further investigated whether GABA receptors in the PVN might mediate the effects of salusin-β in sympathetic inhibition.…”

Nitric Oxide Involvement in Cardiovascular Dysfunctions of Parkinson Disease

“…Regarding the central control of the cardiovascular system, it was observed that nNOS is increased in the paraventricular nucleus of the hypothalamus, an area of cardiovascular control, leading to an increase in GABAergic tone on cardiovascular function and contributing to the lower basal BP values in male 6-OHDA injured rats ( Turossi Amorim et al, 2019 ). By this way, the decreased baseline blood pressure in animals with Parkinsonism by 6-OHDA may be due to a central effect mediated by the NO in the PVN.…”

“…The boxes in red are questions and possible hypotheses. The central illustrations were taken from the cited articles by Ariza et al, 2015b and Turossi Amorim et al, 2019 . The lateral illustrations were taken from BioRender.…”

Recent advances in blood pressure research

“…Investigating the mechanisms of blood pressure regulation was again a focus of a number of articles published in Acta physiologica in the recent year. The research on basic physiological questions and mechanism in model organisms is complemented with studies that include clinical patient data …”