Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to evaluate and compare the effects of simultaneous angiotensin-converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP) inhibition by the vasopeptidase inhibitor omapatrilat (10 and 40 mg x kg(-1) x day(-1)) with those of the selective ACE inhibitor captopril (160 mg x kg(-1) x day(-1)) on survival, cardiac hemodynamics, and cytokine mRNA expression in left ventricular (LV) tissues 4 days after myocardial infarction (MI) in rats. The effects of the co-administration of both B1 and B2 kinin receptor antagonists (2.5 mg x kg(-1) x day(-1) each) with and without omapatrilat were also evaluated to assess the role of bradykinin (BK) during this post-MI period. Both omapatrilat and captopril treatments improve early (4 days) post-MI survival when started 4 h post-MI. The use of kinin receptor antagonists had no significant effect on survival in untreated MI rats and omapatrilat-treated MI rats. This improvement in survival with omapatrilat and captopril is accompanied by a reduced LV end-diastolic pressure (LVEDP) and pulmonary congestion. The use of kinin receptor antagonists had little effect on cardiac hemodynamics or morphologic measurements. Acute MI significantly increased the expression of cardiac cytokines (TNF-alpha, TGF-beta1, and IL-10). Captopril significantly attenuated this activation, while omapatrilat had variable effects: sometimes increasing but generally not changing activation depending on the cytokine measured and the dose of omapatrilat used. The co-administration of both kinin receptor antagonists attenuates the increase in expression of cardiac TNF-alpha and TGF-beta1 after omapatrilat treatment. Taken together, these results would suggest that despite very marked differences in the way these drugs modified the expression of cardiac cytokines, both omapatrilat and captopril improved early (4 days) post-MI survival and cardiac function to a similar extent.
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PMID:Effects of captopril and omapatrilat on early post-myocardial infarction survival and cardiac hemodynamics in rats: interaction with cardiac cytokine expression. 1191 Dec 26

The aim of the present study was to clarify the role of angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) in bradykinin (BK)-induced relaxation and contraction of isolated porcine basilar artery by measuring isometric tension, ACE and NEP activities and their localization. BK induced endothelium-dependent relaxation followed by contraction; however, in the presence of indomethacin BK induced relaxation but not contraction, in contrast, in the presence of L-nitro-arginine BK induced contraction but not relaxation. Captopril and thiorphan increased the p D(2) value for BK-induced relaxation from 8.11 to 9.55 and the p A(2) value for [Thi(5,8), D-Phe(7)]-BK (a B(2)-receptor antagonist) from 6.95 to 7.59. The same treatment increased the p D(2) value for BK-induced contraction from 7.93 to 8.97 and the p A(2) value for [Thi(5,8), D-Phe(7)]-BK from 6.86 to 7.50. Captopril inhibited ACE activity with an IC(50) of 38.0 nM, and thiorphan inhibited NEP and ACE activities with an IC(50) of 1.4 nM and 295.0 nM, respectively. Endothelial denudation decreased the ACE and NEP activities by 76.7% and 15.9%, respectively, and ACE mRNA level by 59.4%, but had no significant effect on NEP mRNA level. These results suggest that BK-induced relaxation and contraction in the porcine basilar artery are enhanced by captopril and thiorphan which predominantly inhibit ACE activity localized on endothelial cells.
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PMID:Role of ACE and NEP in bradykinin-induced relaxation and contraction response of isolated porcine basilar artery. 1201 22


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