Key result
S-nitrosocaptopril administered intravenously (1 mg/kg) reduced mean pulmonary artery pressure by 28% in hypoxic rats, while a 30 mg/kg oral dose significantly reduced it to 17 mmHg.
Why the study?
Does S-nitrosocaptopril reduce pulmonary artery pressure in rats with hypoxic pulmonary hypertension?
Does S-nitrosocaptopril reduce pulmonary artery pressure in rats with hypoxic pulmonary hypertension?
S-nitrosocaptopril demonstrates acute pulmonary vasodepressor effects in a rat model of hypoxic pulmonary hypertension, suggesting potential utility combining direct vasodilation with ACE inhibition.
Hypothesis-generating for S-nitrosocaptopril in hypoxic pulmonary hypertension; extends prior in-vitro data to an in-vivo rat model.
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.
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Tsui et al. (2003) studied Hypoxic pulmonary hypertension. S-nitrosocaptopril (SNOcap) was evaluated on Mean pulmonary artery pressure (MPAP). S-nitrosocaptopril administered intravenously (1 mg/kg) reduced mean pulmonary artery pressure by 28% in hypoxic rats, while a 30 mg/kg oral dose significantly reduced it to 17 mmHg.
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