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
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.