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 x 10(-3) N; n = 13) and of the rat iliac artery (increase of tension, 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, 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.
Tepel
M
M
Universitätsklinik Marienhospital, Medizinische Klinik I, Ruhr-Universität Bochum, Herne, Germany.
Jankowski
J
J
Ruess
C
C
Steinmetz
M
M
van der Giet
M
M
Zidek
W
W
D000143:Acids / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000502:physiology; D002478:Cells, Cultured; D006863:Hydrogen-Ion Concentration; D007083:Iliac Artery / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009994:Osmolar Concentration; D051381:Rats; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*
D000143:Acids; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium