Related Experiment Video
Updated: May 23, 2025

Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension
Published on: April 11, 2016
Inhibition of Sodium/Hydrogen Exchanger-1 in the Right Ventricle and Lung Dysfunction Induced by Experimental
Giuseppina Milano1, Melanie Reinero1, Julien Puyal2,3
1Department Cœur-Vaisseaux, Cardiac Surgery Center University Hospital of Lausanne Switzerland.
Background:
Life-threatening pulmonary arterial hypertension (PAH) still lacks a direct therapeutic approach targeted to the molecular defects associated with the disease. Here, we focus on the impaired regulation of intracellular acidity and sodium/calcium overload by testing the hypothesis that inhibiting NHE-1 (sodium/hydrogen exchanger isoform 1) with rimeporide enables the recovery of pulmonary and right ventricular dysfunctions in the Sugen5416/hypoxia PAH model in rats.
Methods And Results:
Adult Sprague-Dawley male rats (n=44) rats were divided into 2 broad groups: control and Sugen5416/hypoxia. After verifying PAH insurgence in the Sugen5416/hypoxia group by transthoracic echocardiography and pulse-wave Doppler analysis, rats were treated with either 100 mg/kg per day rimeporide or placebo in drinking water for 3 weeks. The functional, morphological (fibrosis and hypertrophy), and biochemical (inflammation, signaling pathways) dysfunctions caused by PAH were partially reverted by rimeporide in both the lungs and myocardium, where the most striking effects were observed in the right ventricle. Rimeporide improved hemodynamics in the pulmonary circulation and in the right ventricle, with decrease in right ventricle hypertrophy, pulmonary vascular remodeling, inflammation, and fibrosis. No effect of rimeporide was detected in control rats. The protective effect of rimeporide was accompanied by decreased p-Akt/Akt (phosphorylated protein kinase B/protein kinase B) ratio and increased autophagy flux mainly in the right ventricle.
Conclusions:
By specifically inhibiting NHE-1, rimeporide at the selected dosage revealed remarkable anti-PAH effects by preventing the functional, morphological, and biochemical deleterious effects of PAH on the right ventricle and lungs. Rimeporide should be considered as a potential treatment for PAH.
More Related Videos
Related Concept Videos
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
Pulmonary Hypertension: Classification and Pathogenesis
There are various classifications for PH, each relating to different underlying causes and also...
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
Antihypertensive Drugs: Vasodilators

