S-nitrosocaptopril: acute in-vivo pulmonary vasodepressor effects in pulmonary hypertensive rats.
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.
Tsui
Debbie Y Y
DY
School of Biomedical Sciences, Department of Physiology and Pharmacology, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
Gambino
Agatha
A
Wanstall
Janet C
JC
D000284:Administration, Oral; D000818:Animals; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D007275:Injections, Intravenous; D008168:Lung / Q000098:blood supply* / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation
D014662:Vasoconstrictor Agents; C060039:S-nitrosocaptopril; D002216:Captopril