Activation of Na+,H+ exchanger produces vasoconstriction of renal resistance vessels

To evaluate the influence of the sodium/proton exchanger (Na+,H+ exchanger) on the constriction of rat resistance vessels and on the iliac artery, the isometric vasoconstrictions of renal resistance vessels and strips from iliac artery derived from Wistar-Kyoto rats were measured using a vessel myograph. The Na+,H+ exchanger was activated by intracellular acidification using propionic acid. Cytosolic pH (pHi) and cytosolic free sodium concentration ([Na+]i) in vascular smooth muscle cells were measured using the fluorescent dye technique. The activation of the Na+,H+ exchanger increased the [Na+]i by 12.4 ± 1.3 mmol/L (n = 8). The activation of the Na+,H+ exchanger caused a contractile response of the renal resistance vessels (increase of tension, 1.5 ± 0.1 × 10−3 N; n = 13) and of the rat iliac artery (increase of tension, 7.5 ± 0.8 × 10−3 N; n = 5). The contractile response after activation of the Na+,H+ exchanger was significantly inhibited in the absence of external sodium or in the presence of amiloride, confirming the involvement of the Na+,H+ exchanger. The contractile response after activation of the Na+,H+ exchanger was significantly reduced in the absence of external calcium, after inhibition of calcium channels by nifedipine, and in the presence of an intracellular calcium antagonist 8-(diethylamino-)-octyl-3,4,5-trimethoxybenzoate (TMB-8), indicating that the activation of the Na+,H+ exchanger consecutively caused transplasma membrane calcium influx. On the other hand, the inhibition of the Na+,Ca2+ exchanger by NiCl2 significantly increased the vasoconstriction of renal resistance vessels after activation of the Na+,H+ exchanger. The activation of the Na+,H+ exchanger produces vasoconstriction by an increased cytosolic sodium concentration, inhibition of the Na+,Ca2+ exchanger, and activation of transplasma membrane calcium influx through potential dependent calcium channels.