The study titled, “Effects of renal denervation on monocrotaline induced pulmonary remodeling,” was published in the journal Oncotarget.
Despite the progress achieved with oral therapies over the last two decades, the prognosis of PAH, especially in patients with advanced right heart failure, remains poor.
Overactivity of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS) — particularly its renal component — are well-known to underlie hypertension. Recent data showed that these systems have a crucial role in the development and progression of PAH, including constriction of the blood vessels, inflammation, and fibrosis (damage and scarring) in the lungs.
RDN is the disruption of renal nerves to treat uncontrolled hypertension. Despite the fact that RDN has been shown to reduce RAAS and SNS activation and may improve cardiac remodeling, its role in PH has not been fully explored and could be an important avenue for developing new therapies.
A research team led by Qijun Shan, MD, PhD, from the Department of Cardiology at the First Affiliated Hospital of Nanjing Medical University, China, used a rat model to study the association of RDN during different periods of PAH.
PAH was induced in the rat model by injecting monocrotaline, a pneumotoxic agent that damages cells in the pulmonary artery, impairing the lungs’ barrier function and causing inflammation, hemorrhaging, ventricular hypertrophy, fibrosis, and eventually failure.
The research team performed RDN at 24 hours (24-hour group) or two weeks (two-week group) after PAH induction. These animals were compared with controls with PAH, but with sham RDN surgery (control group). The researchers collected tissue and blood samples after 35 days.
Results revealed that the collagen volume fraction (typically greater in patients with hypertensive heart disease and an indicator of fibrosis) in the right ventricle, lung tissue, and pulmonary vessel was reduced in the 24-hour group of rats, but not in the two-week group.
The earlier RDN treatment significantly decreased SNS activity and abolished RAAS overactivity. Right ventricular wall thickness (a measure of hypertrophy) was reduced in both groups of rats subjected to RDN. RDN also improved survival rate.
Overall, the study revealed that an earlier RDN is able to attenuate cardio-pulmonary fibrosis, improve heart function, and inhibit endogenous mechanisms involved in pulmonary hypertension. Therefore, “these experimental findings suggest that RDN should be further investigated as a potential approach for treating earlier stage of PAH,” the authors concluded.