S-Nitrosocaptopril: acute in-vivo pulmonary vasodepressor effects in pulmonary hypertensive rats

Abstract

The effects of S-nitrosocaptopril (SNOcap), administered either intravenously or by oral gavage, on pulmonary artery pressure (PAP) were examined in anaesthetised normotensive rats and rats with hypoxic pulmonary hypertension (10% oxygen for 1 week). Mean PAP (MPAP) values in hypoxic and normoxic rats were (mmHg) 26 +/- 1.7 and 15 +/- 1.1, respectively. When given intravenously, 1 mg kg(-1) SNOcap reduced MPAP by 28 and 32% in hypoxic and normoxic rats, respectively. The effects of 2 mg kg(-1) were no greater than those of 1 mg kg(-1). Pulmonary vasodepressor responses reached equilibrium in 1.7 +/- 0.18 min following intravenous administration. When given orally 30 min before the measurement of PAP, 30 mg kg(-1), but not 10 mg kg(-1), significantly reduced MPAP in hypoxic rats to 17 +/- 1.5 mmHg. These in-vivo data are consistent with previous in-vitro data showing that SNOcap has direct pulmonary vasorelaxant properties in both large and small pulmonary arteries and also show that SNOcap causes pulmonary vasodepression in the setting of pulmonary hypertension. Since SNOcap also inhibits pulmonary vascular angiotensin converting enzyme (ACE) in pulmonary blood vessels (previous study), it would be an interesting drug with which to assess the benefits of direct pulmonary vasodilatation combined with ACE inhibition (which attenuates pulmonary vascular remodelling) in a long-term study in pulmonary hypertension.

A nanoparticle delivery vehicle for S-nitroso-N-acetyl cysteine: Sustained vascular response

“…Captopril is an angiotensin-converting enzyme (ACE) inhibitor and is used for hypertension. SNO-captopril is a transnitrosating agent and [81; 82] has been shown to control acute and chronic hypertensive effects more efficiently than captopril in rats [83; 84]. …”

NIR-Triggered On-Demand Nitric Oxide Release for Enhanced Synergistic Phototherapy of Hypoxic Tumor

“…S -Nitrosocaptopril, as a new generation of NO donor, is a kind of SNO and has been widely applied in the clinical treatment for hypertension. , Benefiting from the desirable characteristics of NO release, S -nitrosocaptopril has a potential for application in tumor therapy. However, only a high concentration of NO can lead to the direct killing of tumor cells.…”

Optimization of S-Nitrosocaptopril Monohydrate Storage Conditions Based on Response Surface Method

“…Moreover, S-nitrosocaptopril monohydrate (Cap-NO•H 2 O) is a novel and stable compound based on S-nitrosocaptopril (Cap-NO), which is not only a nitric oxide (NO) donor but also an angiotensin-converting enzyme inhibitor (ACEI). Cap-NO•H 2 O has great potential for the study and possible treatment of numerous diseases such as pulmonary hyperattention [2][3][4], hypertension regardless of renin status, angina pectoris [5] and congestive heart failure [6], acute respiratory distress syndrome [7] and preventing postoperative circulation tumor cells metastasis [8].…”