The soluble guanylate cyclase stimulator, 1-nitro-2-phenylethane, reverses monocrotaline-induced pulmonary arterial hypertension in rats.

Abstract

AIMS:

We examined the effects of treatment with 1-nitro-2-phenylethane (NP), a novel soluble guanylate cyclase stimulator, on monocrotaline (MCT)-induced PAH in rats.

MAIN METHODS:

At day 0, male adult rats were injected with a single subcutaneous (s.c.) dose of monocrotaline (60 mg/kg). Control (CNT) rats received an equal volume of monocrotaline's vehicle only (s.c.). Four weeks later, MCT-treated rats were treated orally for 14 days with NP (50 mg/kg/day) (MCT-NP group) or its vehicle (Tween 2%) (MCT-V group). At the end of the treatment period and before invasive hemodynamic study, rats of all experimental groups were examined by echocardiography.

KEY FINDINGS:

With respect to CNT rats, MCT-V rats showed significant; (1) increases in pulmonary artery (PA) diameter, RV free wall thickness and end-diastolic RV area, and increase of Fulton index; (2) decreases in maximum pulmonary flow velocity, PA acceleration time (PAAT), PAAT/time of ejection ratio, and velocity-time integral; (3) increases in estimated mean pulmonary arterial pressure; (4) reduction of maximal relaxation to acetylcholine in aortic rings, and (5) increases in wall thickness of pulmonary arterioles. All these measured parameters were significantly reduced or even abolished by oral treatment with NP.

SIGNIFICANCE:

NP reversed endothelial dysfunction and pulmonary vascular remodeling, which in turn reduced ventricular hypertrophy. NP reduced pulmonary artery stiffness, normalized the pulmonary artery diameter and alleviated RV enlargement. Thus, NP may represent a new therapeutic or a complementary approach to treatment of PAH.

• Authors: Karoline Gonzaga-Costa, Cássia Rodrigues Roque, Alfredo Augusto Vasconcelos-Silva, Hellida Larissa Sousa-Brito, Conceição Silva Martins, Marta Maria Caetano-Souza, Glória Pinto Duarte, Joyce Kelly Rosário da Silva, Rosivaldo Santos Borges, Armênio Aguiar Dos Santos, Pedro Jorge Caldas Magalhães, Saad Lahlou
• Journal: Life sciences (Life Sci) Vol. 275 Pg. 119334 (Jun 15 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 33711391 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• 1-nitro-2-phenylethane
• Benzene Derivatives
• Monocrotaline
• Soluble Guanylyl Cyclase

Topics

• Animals
• Benzene Derivatives (pharmacology)
• Echocardiography
• Endothelium, Vascular (drug effects)
• Hemodynamics (drug effects)
• Male
• Monocrotaline (antagonists & inhibitors, pharmacology)
• Pulmonary Arterial Hypertension (chemically induced, diagnostic imaging, drug therapy)
• Pulmonary Artery (drug effects)
• Rats
• Rats, Wistar
• Soluble Guanylyl Cyclase (drug effects)
• Vascular Remodeling (drug effects)