Long-term stimulation of cardiac vagal preganglionic neurons reduces blood pressure in the spontaneously hypertensive rat

Author(s)

Moreira, Thiago S. ^[1] ; Antunes, Vagner R. ^[1] ; Falquetto, Barbara ^[2] ; Marina, Nephtali ^{[3, 4]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo, SP - Brazil

^[3] UCL, Ctr Cardiovasc & Metab Neurosci, Div Med, London - England

^[4] UCL, Ctr Cardiovasc & Metab Neurosci, Div Med, Dept Clin Pharmacol & Expt Therapeut, London - England

• Document type: Journal article
• Source: Journal of Hypertension; v. 36, n. 12, p. 2444-2452, DEC 2018.
• Web of Science Citations: 2

Abstract

Background: Arterial hypertension is associated with autonomic nervous system dysfunction. Different interventional strategies have been implemented in recent years for the reduction of sympathetic activity in patients with hypertension. However, the therapeutic benefit of increasing vagal tone in hypertensive patients remains largely unexplored. Objective: Here, we describe the effects of long-term activation of vagal neural pathways on arterial pressure, heart rate arterial pressure variability and spontaneous baroreflex sensitivity in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. Methods: Brainstem vagal preganglionic neurons residing in the dorsal vagal motor nucleus (DVMN) were targeted with a lentiviral vector to induce the expression of an artificial G(s) protein-coupled receptor termed designer receptors exclusively activated by designer drugs (DREADD-Gs). The transduced neurons were activated daily by systemic administration of otherwise inert ligand clozapinen-oxide. Arterial pressure measurements were recorded in conscious freely moving animals after 21 consecutive days of DVMN stimulation. Results: Resting arterial pressure was significantly lower in SHRs expressing DREADD-Gs in the DVMN, compared with control SHRs expressing enhanced green fluorescent protein. No changes in arterial pressure were detected in Wistar rats expressing DREADD-Gs compared with rats expressing enhanced green fluorescent protein in the DVMN. Pharmacogenetic activation of DREADD-Gs-expressing DVMN neurons in SHRs was accompanied with increased baroreflex sensitivity and a paradoxical decrease in cardio-vagal components of heart rate and systolic arterial pressure variability in SHRs. Conclusion: These results suggest that long-term activation of vagal parasympathetic pathways is beneficial in restoring autonomic balance in an animal model of neurogenic hypertension and might be an effective therapeutic approach for the management of hypertension. (AU)

• FAPESP's process: 15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity
• Grantee: Thiago dos Santos Moreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/21991-3 - Salt-induced hypertension: role of purinergic signaling in the neuronal cells at the hypothalamus level, and its correlation with the autonomic nervous system and blood pressure control
• Grantee: Vagner Roberto Antunes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/22069-0 - Amelioration of the brainstem vascular imbalances in an spontaneously hypertensive rats with exercise
• Grantee: Thiago dos Santos Moreira
• Support Opportunities: Regular Research Grants