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S‐Nitrosocaptopril: in vitro characterization of pulmonary vascular effects in rats
Author(s) -
Tsui Debbie Y Y,
Gambino Agatha,
Wanstall Janet C
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705128
Subject(s) - captopril , chemistry , s nitrosoglutathione , sodium nitroprusside , soluble guanylyl cyclase , incubation , angiotensin ii , pharmacology , angiotensin converting enzyme , endocrinology , nitric oxide , medicine , enzyme , biochemistry , guanylate cyclase , blood pressure , glutathione , receptor , organic chemistry
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. SNOcap was equipotent as a vasorelaxant on main (i.d. 2–3 mm) and intralobar (i.d. 600 μm) pulmonary arteries (pIC 50 values: 5.00 and 4.85, respectively). Vasorelaxant responses reached equilibrium rapidly (2–3 min). Pulmonary vasorelaxant responses to SNOcap, like GSNO, were (i) partially inhibited by the soluble guanylate cyclase inhibitor, ODQ (1 H ‐(1,2,4) oxadiazolo(4,3‐ a )‐quinoxalin‐1‐one; 3 μ M ) whereas responses to nitroprusside were abolished and (ii) potentiated by hydroxocobalamin (HCOB; NO· free radical scavenger; 100 μ M ) whereas responses to nitroprusside were inhibited. The relative potencies for pulmonary vasorelaxation compared with inhibition of platelet aggregation were: SNOcap 7 : 1; GSNO 25 : 1; nitroprusside >2000 : 1. SNOcap, like captopril, concentration‐dependently and time‐dependently increased the EC 50 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 (5.6 h) SNOcap was more effective than captopril. 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.British Journal of Pharmacology (2003) 138 , 855–864. doi: 10.1038/sj.bjp.0705128