S-Nitrosocaptopril: In vitro characterization of pulmonary vascular effects in rats

Tsui, D. Y. Y., Gambino, A. and Wanstall, J. C. (2003) S-Nitrosocaptopril: In vitro characterization of pulmonary vascular effects in rats. British Journal of Pharmacology, 138 5: 855-864. doi:10.1038/sj.bjp.0705128

Author Tsui, D. Y. Y.
Gambino, A.
Wanstall, J. C.
Title S-Nitrosocaptopril: In vitro characterization of pulmonary vascular effects in rats
Journal name British Journal of Pharmacology   Check publisher's open access policy
ISSN 0007-1188
Publication date 2003
Sub-type Article (original research)
DOI 10.1038/sj.bjp.0705128
Volume 138
Issue 5
Start page 855
End page 864
Total pages 10
Place of publication United Kingdom
Publisher Nature Publishing Group
Collection year 2003
Language eng
Subject C1
320502 Basic Pharmacology
730106 Cardiovascular system and diseases
1115 Pharmacology and Pharmaceutical Sciences
Abstract 1 On rat isolated pulmonary arteries, vasorelaxation by S-nitrosocaptopril (SNOcap) was compared with S-nitrosoglutathione (GSNO) and nitroprusside, and inhibition by SNOcap of contractions to angiotensin I was compared with the angiotensin converting enzyme (ACE) inhibitor, captopril. 2 SNOcap was equipotent as a vasorelaxant on main (i.d. 2-3 mm) and intralobar (i.d. 600 mum)pulmonary arteries (pIC(50) values: 5.00 and 4.85, respectively). Vasorelaxant responses reached equilibrium rapidly (2-3 min). 3 Pulmonary vasorelaxant responses to SNOcap, like GSNO, were (i) partially inhibited by the soluble guanylate cyclase inhibitor, ODQ (1H-(1,2,4) oxadiazolo(4,3-a)-quinoxalin-1-one; 3 muM) whereas responses to nitroprusside were abolished and (ii) potentiated by hydroxocobalamin (HCOB; NO. free radical scavenger; 100 muM) whereas responses to nitroprusside were inhibited. 4 The relative potencies for pulmonary vasorelaxation compared with inhibition of platelet aggregation were: SNOcap 7: 1; GSNO 25: 1; nitroprusside > 2000:1. 5 SNOcap, like captopril, concentration-dependently and time-dependently increased the EC50 for angiotensin I but not angiotensin II. The dependence on incubation time was independent of the presence of tissue but differed for SNOcap and captopril. This difference reflected the slow dissociation of SNOcap and instability of captopril, and precluded a valid comparison of the potency of the two drugs. After prolonged incubation (greater than or equal to 5.6 h) SNOcap was more effective than captopril. 6 Thus, in pulmonary arteries SNOcap (i) possesses NO donor properties characteristic of S-nitrosothiols but different from nitroprusside and (ii) inhibits ACE at least as effectively as captopril. These properties suggest that SNOcap could be valuable in the treatment of pulmonary hypertension.
Keyword Pharmacology & Pharmacy
Nitric Oxide Donors
Angiotensin Converting Enzyme Inhibitors
Rat Pulmonary Artery
Platelet Aggregation
Angiotensin-converting Enzyme
Mediated Relaxations
Anococcygeus Muscle
Hypertensive Rats
Guanylyl Cyclase
Superoxide Anion
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2004 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 15 times in Scopus Article | Citations
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Created: Wed, 15 Aug 2007, 02:25:42 EST