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NO/cGMP pathway in adrenomedullin mediated cardioprotection in mouse

Hamid, Shabaz A., Totzeck, M., Drexhage, C., Thompson, I., Fowkes, R. C., Rassaf, T. and Baxter, Gary Francis 2007. NO/cGMP pathway in adrenomedullin mediated cardioprotection in mouse. Journal of Molecular and Cellular Cardiology 42 (6) , S195. 10.1016/j.yjmcc.2007.03.592

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Abstract

Adrenomedullin (AM) limits experimental reperfusion injury due to Akt/eNOS signalling. We hypothesised that AM increases the NO pool and that cardioprotection is dependent on activation of soluble guanylyl cyclase (sGC). Isolated hearts from CD31 mice were Langendorff-perfused. The left coronary artery was occluded for 30 min followed by 60 min reperfusion (R). AM 10 nM was administered from 15 min ischemia until 10 min reperfusion. Coronary effluent and LV myocardial samples were collected for nitrite (NO2−), nitrate (NO3−) and nitrosothiol (RNOS) analysis using reductive chemiluminescence. To examine the role of sGC, further hearts received the inhibitor ODQ 2 μM, alone or in combination with AM. CAUC μM min2 mL− 1 LV myocardium μM NO2− NO3− NO2− NO3− 10R 60R 10R 60R Con 14.4 ± 2.8 6.1 ± .04 4.2 ± .8 4.6 ± .5 3.3 ± .3 3.8 ± .4 AM 29.2 ± 3.9* 7.2 ± .01* 3.9 ± .3 5.7 ± .4* 4.3 ± .7* 4.8 ± .5* Full-size table Table options * View in workspace * Download as CSV CAUC = total clearance in coronary effluent at reperfusion. n = 4–5. *p < 0.05 1-way ANOVA vs. control. AM increased RNOS 10 min after reperfusion (411 ± 60 nM vs. 221 ± 36 nM control, p < 0.05) and RV cGMP was elevated by 71% versus baseline. Infarct reduction by AM was blunted by sGC inhibition (AM 12.2 ± 2.3% vs. AM + ODQ 28.9 ± 4.3%, control 35.4 ± 2.7%, p < 0.05). We conclude that AM increases myocardial NO bioavailability and provides protection via the NO/sGC/cGMP pathway.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Uncontrolled Keywords: Ischemia/reperfusion; Cardioprotection; Nitric oxide
Publisher: Elsevier
ISBN: 0022-2828
ISSN: 0022-2828
Last Modified: 04 Jun 2017 01:57
URI: http://orca.cf.ac.uk/id/eprint/6548

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