Endothelin‐1 shifts the mediator of bradykinin‐induced relaxation from NO to H2O2 in resistance arteries from patients with cardiovascular disease
| Autor: | Leurgans, Thomas M, Bloksgaard, Maria, Brewer, Jonathan R, Bagatolli, Luis A, Fredgart, Maise H, Rosenstand, Kristoffer, Hansen, Maria L, Rasmussen, Lars M, Irmukhamedov, Akhmadjon, De Mey, Jo G R |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Endothelin-1 Arteries Hydrogen Peroxide In Vitro Techniques Bradykinin Nitric Oxide Research Papers Bradykinin/pharmacology Cardiovascular Diseases/metabolism Arteries/drug effects Cardiovascular Diseases Nitric Oxide/metabolism Humans Female Endothelin-1/pharmacology Hydrogen Peroxide/metabolism Aged |
| Zdroj: | Leurgans, T M, Bloksgaard, M, Brewer, J R, Bagatolli, L A, Fredgart, M H, Rosenstand, K, Hansen, M L, Rasmussen, L M, Irmukhamedov, A & De Mey, J G R 2016, ' Endothelin-1 shifts the mediator of bradykinin-induced relaxation from NO to H2 O2 in resistance arteries from patients with cardiovascular disease ', British Journal of Pharmacology, vol. 173, no. 10, pp. 1653-1664 . https://doi.org/10.1111/bph.13467 |
| DOI: | 10.1111/bph.13467 |
| Popis: | Background and Purpose We tested the hypothesis that in resistance arteries from cardiovascular disease (CVD) patients, effects of an endothelium-dependent vasodilator depend on the contractile stimulus. Experimental Approach Arteries dissected from parietal pericardium of cardiothoracic surgery patients were studied by myography and imaging techniques. Segments were sub-maximally contracted by K +, the TxA 2 analogue U46619 or endothelin-1 (ET-1). Key Results Relaxing effects of Na-nitroprusside were comparable, but those of bradykinin (BK) were bigger in the presence of ET-1 compared with K + or U46619. BK-induced relaxation was (i) abolished by L-NAME in K +-contracted arteries, (ii) partly inhibited by L-NAME in the presence of U46619 and (iii) not altered by indomethacin, L-NAME plus inhibitors of small and intermediate conductance calcium-activated K + channels, but attenuated by catalase, in ET-1-contracted arteries. This catalase-sensitive relaxation was unaffected by inhibitors of NADPH oxidases or allopurinol. Exogenous H 2O 2 caused a larger relaxation of ET-1-induced contractions than those evoked by K + or U46619 in the presence of inhibitors of other endothelium-derived relaxing factors. Catalase-sensitive staining of cellular ROS with CellROX Deep Red was significantly increased in the presence of both 1 μM BK and 2 nM ET-1 but not either peptide alone. Conclusions and Implications In resistance arteries from patients with CVD, exogenous ET-1 shifts the mediator of relaxing responses to the endothelium-dependent vasodilator BK from NO to H 2O 2 and neither NADPH oxidases, xanthine oxidase nor NOS appear to be involved in this effect. This might have consequences for endothelial dysfunction in conditions where intra-arterial levels of ET-1 are enhanced. |
| Databáze: | OpenAIRE |
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