Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inflammatory effects of enalaprilat and cilazaprilat were tested in an experimental model of ovalbumin-sensitised guinea-pigs. Enalaprilat, but not cilazaprilat, enhanced the ovalbumin-induced inflammatory skin responses. The effect of enalaprilat was dose-dependent. Enalaprilat significantly increased the skin content of substance P and histamine. Cilazaprilat did not alter the level of these inflammatory mediators. Enalaprilat, applied locally, but not cilazaprilat, enhanced the inflammatory reactions caused by intradermal injections of allergen and substance P. Both angiotensin converting enzyme (ACE) inhibitors enhanced the inflammatory skin response evoked by bradykinin. Our study strongly indicates that enalaprilat has pro-inflammatory properties, whereas the new long-acting ACE inhibitor cilazaprilat does not. This might give a better safety profile of cilazaprilat.
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PMID:Enalaprilat, but not cilazaprilat, increases inflammatory skin reactions in guinea-pigs. 171 72

ACE-inhibitors have for some time been used in the treatment of hypertension. Apart from inhibiting the conversion of angiotensin I to II, the drugs also affect the metabolism of some inflammatory agents, like bradykinin and substance P. Egg albumin (EA)-sensitized guinea pigs were pretreated with the ACE-inhibitors. Measurement of flare and wheal areas induced by an intradermal injection of EA, showed that enalaprilat significantly increased, whereas cilazaprilat slightly decreased, the reaction area. Enalaprilat also showed an enhancement in histamine and substance P (SP) contents in the skin. In vitro incubation of guinea pig biopsies with enalaprilat potentiated EA- but not SP-induced histamine release. The EA-induced effect was abolished if the animals were pretreated with capsaicin. The conclusion is that cilazaprilat, in contrast to enalaprilat, does not potentiate inflammatory reactions in the guinea pig.
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PMID:Enalaprilat versus cilazaprilat: a comparison of allergic skin reactions in the guinea pig. 171 46

Two non-sulfur containing ACE-inhibitors were tested concerning their local effect on experimental dermatitis in ovalbumin-sensitized guinea pigs. Enalaprilat but not cilazaprilat potentiated the ovalbumin-evoked inflammatory response. Furthermore, enalaprilat clearly enhanced the erythema evoked by substance P, whereas cilazaprilat did not. Concerning, the bradykinin-evoked erythema, enalaprilat significantly potentiated the response, whereas cilazaprilat only caused a slight increase. Our results suggest that different affinities for peptidases involved in degradation of inflammatory peptides can explain differences between the pro-inflammatory properties of enalaprilat and cilazaprilat.
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PMID:Effects of cilazaprilat and enalaprilat on experimental dermatitis in guinea pigs. 171 14

The effects of dihydropyridine Ca2+ channel blockers (DHP) and ACE inhibitors on superoxide formation and nitric oxide (NO) bioavailability were compared in human EA.Hy926 endothelial cells (EC). EC were stimulated 4 h with angiotensin II (Ang II, 10 nM) +/- study drugs. Specific superoxide formation was measured by lucigenin-enhanced chemiluminescence, reduction of cytochrome c and rhodamine-123 fluorescence. Free NO release was determined with an amperometric NO sensor. NADPH oxidase subunits expression was examined with Western Blot. In untreated EC the intracellular superoxide is -64.3 +/- 6.0% decreased compared to Ang II stimulated EC. Elevated extracellular superoxide formation was on a -43.0 +/- 1.7% lower level in untreated EC. The DHP Ca2+-channel agonist BayK8644 and ACE inhibitors captopril and ramiprilat led extracellular superoxide concentration to control level. Enalaprilat blocked extracellular superoxide, the DHP amlodipine and nisoldipine prevented intracellular increases only (n = 8-9, p < 0.05). Icatibant (HOE 140), a kinin-B2 receptor antagonist, attenuated antioxidant actions of all tested agents except of nisoldipine. Ang II-induced superoxide was elevated by the phorbolester PMA and blocked by the protein kinase C (PKC) inhibitor chelerythrine. Suppression of substance P-evoked NO release by Ang II (>70%, n = 6) was reversed by the PKC inhibitor chelerythrine, the DHP amlodipine and nisoldipine and the ACE inhibitor ramiprilat. Further, Ang II reduces Nox-4 expression by 34.5 +/- 4.9. Nox-2 expression was not regulated. DHP and ACE inhibitors exert different antioxidant effects in human EC stimulated with Ang II, but both improve NO bioavailability via bradykinin and modulation of redox-regulating enzymes.
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PMID:Antioxidant and nitric oxide-sparing actions of dihydropyridines and ACE inhibitors differ in human endothelial cells. 1622 25