ACTIVATION OF NA+,H+ EXCHANGER PRODUCES VASOCONSTRICTION OF RENAL RESISTANCE VESSELS

To evaluate the influence of the sodium/proton exchanger (Naf,Hf excha nger) on the constriction of rat resistance vessels and on the iliac a rtery, 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 intrac ellular acidification using propionic acid. Cytosolic pH (pH(i)) and c ytosolic free sodium concentration ([Na+](i)) in vascular smooth muscl e cells were measured using the fluorescent dye technique. The activat ion of the Na+,H+ exchanger increased the [Na+](i) by 12.4 +/- 1.3 mmo l/L (n = 8). The activation of the Na+,H+ exchanger caused a contracti le response of the renal resistance vessels (increase of tension, 1.5 +/- 0.1 x 10(-3) N; n = 13) and of the rat iliac artery (increase of t ension, 7.5 +/- 0.8 x 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, confirmin g the involvement of the Na+,H+ exchanger. The contractile response af ter activation of the Na+,H+ exchanger was significantly reduced in th e absence of external calcium, after inhibition of calcium channels by nifedipine, and in the presence of an intracellular calcium antagonis t 8-(diethylamino-)- octyl-3,4,5-trimethoxybenzoate (TMB-8), indicatin g that the activation of the Na+,H+ exchanger consecutively caused tra nsplasma membrane calcium influx. On the other hand, the inhibition of the Na+,Ca2+ exchanger by NiCl2 significantly increased the vasoconst riction of renal resistance vessels after activation of the Na+,H+ exc hanger. The activation of the Na+,H+ exchanger produces vasoconstricti on by an increased cytosolic sodium concentration, inhibition of the N a+,Ca2+ exchanger, and activation of transplasma membrane calcium infl ux through potential dependent calcium channels. Am J Hypertens 1998;1 1:1214-1221 (C) 1998 American Journal of Hypertension, Ltd.