Na+/H+ exchange subtype 1 inhibition reduces endothelial dysfunction in vessels from stunned myocardium

Citation
Jd. Symons et S. Schaefer, Na+/H+ exchange subtype 1 inhibition reduces endothelial dysfunction in vessels from stunned myocardium, AM J P-HEAR, 281(4), 2001, pp. H1575-H1582
Citations number
33
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
ISSN journal
03636135 → ACNP
Volume
281
Issue
4
Year of publication
2001
Pages
H1575 - H1582
Database
ISI
SICI code
0363-6135(200110)281:4<H1575:NES1IR>2.0.ZU;2-P
Abstract
Myocardial ischemia and reperfusion cause myocyte and vascular dysfunction, frequently termed "stunning." We hypothesized that inhibiting the Na+/H+ e xchanger subtype 1 isoform (NHE1) during ischemia and reperfusion limits my ocardial and coronary microvascular stunning. Anesthetized rats completed 2 x 10-min coronary artery occlusions separated by 5-min of reperfusion, fol lowed by 15 or 60 min of reperfusion. Vehicle (saline) or the NHE1 inhibito r cariporide (HOE-642) was administered 15 min before ischemia and was cont inued throughout each protocol. After reperfusion, hearts were excised, and the reactivity of resistance arteries (internal diameter, similar to 120 m um) was assessed. The first derivative of left ventricular (LV) pressure, L V developed pressure, and LV systolic wall thickening were depressed (P < 0 .05) similarly in vehicle- and cariporide-treated rats during ischemia and after 15 or 60 min of reperfusion compared with sham-operated animals that were not exposed to ischemia (i.e., controls). In vessels obtained after 15 min of reperfusion, the maximal response to acetylcholine-induced relaxati on (10(-8)-10(-4) M) was blunted (P < 0.05) in vessels from vehicle-(simila r to 35%) and cariporide-treated rats (similar to 55%) compared with contro ls (similar to 85%). However, the percent relaxation to acetylcholine was g reater (P < 0.05) in cariporide-treated rats compared with vehicle-treated rats, Maximal contractile responses to endothelin-1 (10(-11)-10(-7) M) were increased (P < 0.05) similarly in vehicle- and cariporide-treated rats com pared with controls. Relaxation to sodium nitroprusside (10(-4) M) was not different among groups. Results were similar in vessels obtained from anima ls after 60 min of reperfusion. These findings suggest that NHE1 inhibition before coronary occlusion lessens ischemia-induced microvascular dysfuncti on for 15-60 min after reperfusion. but does not alter myocardial contracti le function in the area at risk.