Ventromedial Hypothalamus Activation Aggravates Hypertension Myocardial Remodeling Through the Sympathetic Nervous System

Abstract

Background: The ventromedial hypothalamus (VMH) is an important nuclei in responding to emotional stress, and emotional stress is a risk factor for cardiovascular diseases. However, the role of the VMH in cardiovascular diseases remains unknown. This study aimed to investigate the effects and underlying mechanisms of VMH activation on hypertension related cardiac remodeling in two-kidney-one-clip (2K1C) hypertension (HTN) rats.Methods: Eighteen male Sprague-Dawley rats were injected with AAV-hSyn-hM3D(Gq) into the VMH at 0 weeks and then randomly divided into three groups: (1) sham group (sham 2K1C + saline i.p. injection); (2) HTN group (2K1C + saline i.p. injection); (3) HTN+VMH activation group (2K1C + clozapine-N-oxide i.p. injection). One week later, rats were subjected to a sham or 2K1C operation, and 2 weeks later rats were injected with clozapine-N-oxide or saline for 2 weeks.Results: In the HTN+VMH activation group, FosB expression was significantly increased in VMH sections compared with those of the other two groups. Compared to the HTN group, the HTN+VMH activation group showed significant: (1) increases in systolic blood pressure (SBP); (2) exacerbation of cardiac remodeling; and (3) increases in serum norepinephrine levels and sympathetic indices of heart rate variability. Additionally, myocardial RNA-sequencing analysis showed that VMH activation might regulate the HIF-1 and PPAR signal pathway and fatty acid metabolism. qPCR results confirmed that the relative mRNA expression of HIF-1α was increased and the PPARα and CPT-1 mRNA expression were decreased in the HTN+VMH activation group compared to the HTN group.Conclusions: VMH activation could increase SBP and aggravate cardiac remodeling possibly by sympathetic nerve activation and the HIF-1α/PPARα/CPT-1 signaling pathway might be the underlying mechanism.

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“…5‐min segment of ECG was used for HRV analysis (LabChart 8.0, AD Instruments). The power spectral variables including the low‐frequency component (LF, 0.20–0.75 Hz), the high‐frequency component (HF, 0.75–2.5 Hz), and the LF/HF ratio were calculated as previously described 19,36 …”

Triglyceride-Glucose Index for the Diagnosis of Metabolic Syndrome: A Cross-Sectional Study of 298,652 Individuals Receiving a Health Check-Up in China

“…By disrupting the surface of the endothelial glycosides, this accelerates the changes in vascular endothelial cells, leading to invasion by inflammatory cells and diminishing blood-vessel density. Second, IR stimulates pro-opiomelanocortin (POMC)-releasing neurons in the arcuate nucleus of the hypothalamus, and activates glutamatergic neurons and neurons that express melanocortin 4 receptor (MC4R) in the paraventricular nucleus; thus enhancing the overall activity of the sympathetic nervous system [ 42 , 43 ]. The vasodilatory effect observed in hypertensive patients is thus impaired, with sympathetic nerve activation three times that in normal, unaffected individuals [ 44 ].…”

Brain nuclear receptors and cardiovascular function

“…In contrast, VMH activation by electronic stimulation or drug injection could increase the SNS activity [276,277]. One study showed that activation of the VMH, using the chemogenetic tool, the Designer Receptors Exclusively Activated Designer Drugs (DREADDs), exacerbated cardiac remodeling and increased systolic blood pressure in hypertension rats via increased the sympathetic nervous system activity [278]. VMH is an important nucleus in responding to emotional stress, which is also a risk factor for CVDs [279].…”