HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/4/H1814    most recent 00220.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Kusmic, C. Articles by Sambuceti, G. Search for Related Content PubMed PubMed Citation Articles by Kusmic, C. Articles by Sambuceti, G.

Paradoxical coronary microcirculatory constriction during ischemia: a synergic function for nitric oxide and endothelin

¹Institute of Clinical Physiology Consiglio Nazionale delle Ricerche and ²Scuola Superiore Sant'Anna, Pisa, Italy; and ³Department of Internal Medicine, Division of Nuclear Medicine, University of Genova, Genova, Italy

Submitted 1 March 2006 ; accepted in final form 20 April 2006

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 min (protocol 1), or it was reduced to 30 mmHg over two intervals, between the 20- and 40-min marks (protocol 2) or from the 20-min 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 N^G-nitro-L-arginine methyl ester (L-NAME) (2.7-fold) or the ET_A antagonist BQ-610 (2.8 fold). The ET_B 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 ET_B2-mediated tonic vasoconstriction through ET_A activation. The negative feedback mechanism on ET_B2 subsides during hypotension, and the ensuing vasoconstriction is ascribed to ET-1 activating ET_A and ET_B2 and reactive nitrogen oxide species originating from ROS-NO interaction.

coronary circulation; reactive oxygen species; vasomotor tone

This article has been cited by other articles:

				A. L'Abbate, D. Neglia, C. Vecoli, M. Novelli, V. Ottaviano, S. Baldi, R. Barsacchi, A. Paolicchi, P. Masiello, G. S. Drummond, et al. Beneficial effect of heme oxygenase-1 expression on myocardial ischemia-reperfusion involves an increase in adiponectin in mildly diabetic rats Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3532 - H3541. [Abstract] [Full Text] [PDF]