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The endothelial function of children with and without vascular disease, consisting of 41 controls, 24 with Kawasaki disease (KD), and 46 with diabetes mellitus (DM), was examined. Age at examination ranged from 3 to 23 years (mean, 12.0 +/- 4.7). The flow-mediated dilatation (FMD) and intima-media complex in the common carotid artery were measured. In controls age at examination was not associated with FMD or intima-media complex. FMD significantly decreased in children with KD and DM compared with the control group (control vs KD or DM: 11.7 +/- 14.7 vs 3.0 +/- 11.0 or 6.4 +/- 8.5%, respectively; p < 0.05). However, there was no significant difference for intima-media complex among the groups. Furthermore, FMD in KD patients with coronary arterial aneurysm was lower than that in KD patients without aneurysm (-0.5 +/- 9.2 vs 8.3 +/- 9.1%, p < 0.05). In DM patients, FMD in the high HbA1c group (HbA1c = 7%) was lower than that in the normal HbA1c group (HbA1c < 7%) (4.8 +/- 8.1 vs 11.4 +/- 7.8%, p < 0.05). In conclusion, FMD detected endothelial impairment in children with KD or type 1 DM regardless of overt vascular complications, and FMD impairment occurs prior to intima-media complex thickening. By measuring both FMD and intima-media complex, useful information for predicting vascular complications may be obtained.

The Na(+)/H(+) exchanger (NHE) inhibitor cariporide has a cardioprotective effect in various animal models of myocardial ischemia-reperfusion. Recent studies have suggested that cariporide interacts with mitochondrial Ca(2+) overload and the mitochondrial permeability transition (MPT); however, the precise mechanisms remain unclear. Therefore, we examined whether cariporide affects mitochondrial Ca(2+) overload and MPT. Isolated adult rat ventricular myocytes were used to study the effects of cariporide on hypercontracture induced by ouabain or phenylarsine oxide (PAO). Mitochondrial Ca(2+) concentration ([Ca(2+)](m)) and the mitochondrial membrane potential (DeltaPsi(m)) were measured by loading myocytes with rhod-2 and JC-1, respectively. We also examined the effect of cariporide on the MPT using tetramethylrhodamine methyl ester (TMRM) and oxidative stress generated by laser illumination. Cariporide (1 microM) prevented ouabain-induced hypercontracture (from 40 +/- 2 to 24 +/- 2%, P < 0.05) and significantly attenuated ouabain-induced [Ca(2+)](m) overload (from 149 +/- 6 to 121 +/- 5% of the baseline value, P < 0.05) but did not affect DeltaPsi(m). These results indicate that cariporide attenuates the [Ca(2+)](m) overload without the accompanying depolarization of DeltaPsi(m). Moreover, cariporide increased the time taken to induce the MPT (from 79 +/- 11 to 137 +/- 20 s, P < 0.05) and also attenuated PAO-induced hypercontracture (from 59 +/- 3 to 50 +/- 4%, P < 0.05). Our data indicate that cariporide attenuates [Ca(2+)](m) overload and MPT. Thus these effects might potentially contribute to the mechanisms of cardioprotection afforded by NHE inhibitors.

within the myocytes. In contrast, mammalian atrial myocytes do not have a well developed t-tubular system, and the coupling between the L-type Ca 2+ channels in the sarcolemma and the junctional SR occurs around the periphery of the myocytes [6][7][8]. A confocal imaging of [Ca 2+ ] i has shown that in mammalian atrial myocytes during E-C coupling, an increase in [Ca 2+ ] i can be observed in the peripheral regions of the cell before it spreads to the center [9][10][11]. Furthermore, in spite of a poorly developed t-tubular system, ryanodine receptors (RyR) are present at seemingly equal abundance through atrial myocytes [11][12][13]. These observations strongly suggest that many RyR in the central SR are not associated with L-type Ca 2+ channels. It has been proposed

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