| Autor: |
Kusmic, Claudia, Lazzerini, Guido, Coceani, Flavio, Barsacchi, Renata, L'Abbate, Antonio, Sambuceti, Gianmario |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Heart & Circulatory Physiology; Oct2006, Vol. 291 Issue 4, pH1814-H1821, 7p, 1 Diagram, 3 Charts, 4 Graphs |
| Abstrakt: |
A paradoxical microcirculatory constriction has been observed in hearts of patients with ischemia, secondary to coronary stenosis. Here, using the isolated mouse heart (Langendorff), we examined the mechanism of this response, assuming involvement of nitric oxide (NO) and endothelin-1 (ET-1) systems. Perfusion pressure was maintained at 65 mmHg for 70 mm (protocol 1), or it was reduced to 30 mmHg over two intervals, between the 20- and 40-mm marks (protocol 2) or from the 20-mm mark onward (protocol 3). In protocol 1, coronary resistance (CR) remained steady in untreated heart, whereas it progressively increased during treatment with the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (2.7-fold) or the ETA antagonist BQ-610 (2.8 fold). The ETB antagonist BQ-788 had instead no effect by itself but curtailed vasoconstriction to BQ-610. In protocol 2, hypotension raised CR by 2.2-fold. This response was blunted by reactive oxygen species (ROS) scavengers (mannitol and superoxide dismutase plus catalase) and was converted into vasodilation by L-NAME, BQ-610, or BQ-788. Restoration of normal pressure was followed by vasodilation and vasoconstriction, respectively, in untreated and treated preparations. In protocol 3, CR progressively increased with hypotension in the absence but not presence of L- NAME or BQ-610. We conclude that the coronary vasculature is normally relaxed by two concerted processes, a direct action of NO and ET-1 curtailing an ETB2-mediated tonic vasoconstriction through ETA activation. The negative feedback mechanism on ETB2 subsides during hypotension, and the ensuing vasoconstriction is ascribed to ET-1 activating ETA and ETB2 and reactive nitrogen oxide species originating from ROS-NO interaction. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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