Soluble guanylate cyclase stimulator, trans-4-methoxy-β-nitrostyrene, has a beneficial effect in monocrotaline-induced pulmonary arterial hypertension in rats.

Abstract

The soluble guanylate cyclase (sGC)/GMPc pathway plays an important role in controlling pulmonary arterial hypertension (PAH). We investigated whether the novel sGC stimulator trans-4-methoxy-β-nitrostyrene (T4MN), ameliorates monocrotaline (MCT)-induced PAH. At Day 0, rats were injected with MCT (60 mg/kg, s. c.). Control (CNT) rats received an equal volume of monocrotaline vehicle only (s.c.). Four weeks later, MCT-treated rats were orally treated for 14 days with T4MN (75 mg/kg/day) (MCT-T4MN group) or its vehicle (MCT-V group), and with sildenafil (SIL; 50 mg/kg) (MCT-SIL group). Compared to the CNT group, MCT treatment induced a significant increase in both the Fulton index and RV systolic pressure but significantly reduced the maximum relaxation induced by acetylcholine. Indeed, MCT treatment increased the wall thickness of small and larger pulmonary arterioles. Oral treatment with T4MN and SIL reduced the Fulton index and RV systolic pressure compared to the MCT-V group. Maximum relaxation induced by acetylcholine was significantly enhanced in MCT-SIL group. Both T4MN and SIL significantly reduced the enhanced wall thickness of small and larger pulmonary arterioles. Treatment with T4MN has a beneficial effect on PAH by reducing RV systolic pressure and consequently right ventricular hypertrophy, and by reducing pulmonary artery remodeling. T4MN may represent a new therapeutic or complementary approach for the treatment of PAH.

• Authors: Karoline Gonzaga-Costa, Alfredo Augusto Vasconcelos-Silva, Matyelle Jussára Rodrigues-Silva, Conceição da Silva Martins Rebouça, Glória Pinto Duarte, Rosivaldo Santos Borges, Pedro Jorge Caldas Magalhães, Saad Lahlou
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 897 Pg. 173948 (Apr 15 2021) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 33609564 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• 4-methoxy-beta-nitrostyrene
• Enzyme Activators
• Styrenes
• Monocrotaline
• Soluble Guanylyl Cyclase

Topics

• Animals
• Arterioles (drug effects, enzymology, physiopathology)
• Disease Models, Animal
• Enzyme Activation
• Enzyme Activators (pharmacology)
• Hypertension, Pulmonary (chemically induced, drug therapy, enzymology, physiopathology)
• Hypertrophy, Right Ventricular (enzymology, physiopathology, prevention & control)
• Lung (blood supply)
• Monocrotaline
• Signal Transduction
• Soluble Guanylyl Cyclase (metabolism)
• Styrenes (pharmacology)
• Vascular Remodeling (drug effects)
• Vasodilation (drug effects)
• Ventricular Dysfunction, Right (enzymology, physiopathology, prevention & control)
• Ventricular Function, Right (drug effects)
• Ventricular Remodeling (drug effects)