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Review
. 2020 Nov 22;9(11):2521.
doi: 10.3390/cells9112521.

Neurohormonal Modulation as a Therapeutic Target in Pulmonary Hypertension

Inés García-Lunar  1   2   3 , Daniel Pereda  3   4 , Borja Ibanez  1   3   5 , Ana García-Álvarez  1   3   4
Affiliations
Review

Neurohormonal Modulation as a Therapeutic Target in Pulmonary Hypertension

Inés García-Lunar et al. Cells. .

Abstract

The autonomic nervous system (ANS) and renin-angiotensin-aldosterone system (RAAS) are involved in many cardiovascular disorders, including pulmonary hypertension (PH). The current review focuses on the role of the ANS and RAAS activation in PH and updated evidence of potential therapies targeting both systems in this condition, particularly in Groups 1 and 2. State of the art knowledge in preclinical and clinical use of pharmacologic drugs (beta-blockers, beta-three adrenoceptor agonists, or renin-angiotensin-aldosterone signaling drugs) and invasive procedures, such as pulmonary artery denervation, is provided.

Keywords: adrenoceptor signaling; animal models; denervation; pulmonary hypertension; sympathetic regulation.

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Conflict of interest statement

There are no conflicts of interest regarding this work other that Borja Ibanez and Ana García-Álvarez are co-inventors of a patent for the use of beta-3 agonists for the treatment of pulmonary hypertension.

Figures

Figure 1
Figure 1
Schematic figure summarizing neurohormonal activation in pulmonary hypertension (PH) and pharmacologic and invasive treatments targeting the autonomic nervous system (ANS)/ renin-angiotensin-aldosterone system (RAAS) in this condition. (A) Microphotograph of pulmonary vascular remodeling in experimental pulmonary arterial hypertension (PAH) secondary to systemic-to-pulmonary shunt (in piglets). Black arrows point to a plexiform lesion, one of the histopathological hallmarks of pulmonary arterial hypertension (PAH); (B–D). Figures of parasternal long-axis transthoracic echocardiograms illustrating the spectrum of patients with PH secondary to heart failure (HF). (B) A patient with HF with reduced ejection fraction (secondary to dilated cardiomyopathy): (C) HF with preserved ejection fraction (secondary to hypertrophic cardiomyopathy); and (D) HF secondary to valvular heart disease (severe aortic regurgitation). ACE-I, angiotensin-converting enzyme inhibitors; ACE2+, angiotensin-converting enzyme stimulator; AR, adrenergic receptor; ARB, angiotensin receptor blocker; βB, beta-blocker; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; MRA, mineralocorticoid receptor antagonist; PADN, pulmonary artery denervation; RDN, renal denervation; SGB, sympathetic ganglion block; VNS, vagal nerve stimulation.
See this image and copyright information in PMC

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