Chronic Intermittent Hypobaric Hypoxia Reduces Hypothalamic N-Methyl-d-Aspartate Receptor Activity and Sympathetic...

Area of Science:

• Physiology
• Cardiovascular Research
• Neuroscience

Background:

• Hypertension is a major cardiovascular risk factor.
• The hypothalamic renin-angiotensin system (RAS) plays a role in blood pressure regulation.
• Chronic intermittent hypobaric hypoxia (CIHH) has shown potential antihypertensive effects.

Purpose of the Study:

• To investigate the role of the hypothalamic RAS in the antihypertensive effect of CIHH.
• To determine the impact of CIHH on hypothalamic N-Methyl-d-Aspartate Receptor (NMDAR) activity and sympathetic outflow in spontaneously hypertensive rats (SHRs).

Main Methods:

• SHRs and Wistar-Kyoto rats were exposed to CIHH (simulating 4,000m altitude for 5 hours/day) for 35 days.
• Measurements included blood pressure, RAS components (Angiotensin II, Ang 1-7), NMDAR activity in the hypothalamic paraventricular nucleus (PVN), and sympathetic nerve activity.
• Pharmacological interventions (A779, Angiotensin II, Ang 1-7) were used to elucidate mechanisms.

Main Results:

• CIHH significantly reduced systolic, diastolic, and mean arterial blood pressure in SHRs, with sustained effects post-treatment.
• CIHH reversed alterations in the hypothalamic ACE/AngII/AT1 and ACE2/Ang1-7/Mas axes in SHRs.
• CIHH decreased pre- and postsynaptic NMDAR activity in PVN presympathetic neurons of SHRs, an effect mimicked by Ang 1-7 and blocked by A779 or AngII.

Conclusions:

• CIHH exerts an antihypertensive effect in SHRs by modulating hypothalamic RAS activity.
• CIHH reduces sympathetic outflow and blood pressure via decreased ACE/AngII/AT1 axis activity and increased ACE2/Ang1-7/Mas axis activity.
• CIHH's antihypertensive action involves the reduction of NMDAR activity in PVN presympathetic neurons.