Atrial natriuretic peptide and cGMP inhibit Na+/H+ antiporter in vascular smooth muscle cells in culture.
The aim of the present paper was to study the mechanisms of the inhibitory effect of atrial natriuretic peptide (ANP) on the sustained contraction phase of vascular smooth muscle cells (VSMC). Specifically, the potential role of ANP on the Na+/H+ antiporter and Na+ transport systems was investigated. Both ANP and 8-bromo cGMP inhibited 22Na+ uptake and decreased intracellular Na ([Na+]i) in VSMC, an effect that was mimicked by the specific Na+/H+ antiporter inhibitor, hexamethylen amiloride (HMA). The effect of ANP was not additive with HMA, therefore suggesting that both inhibit the same 22Na+ transport pathway. On the other hand, the inhibition of 22Na+ accumulation by ANP was additive with the inhibition by furosemide or bumetanide, thus suggesting that both drugs act on different Na+ exchange systems. In HEPES-buffered medium, ANP, cGMP, and HMA significantly inhibited the AVP-induced intracellular alkalinization, an effect which was associated with significant inhibition of the AVP-induced shape change. In bicarbonate buffered medium, ANP and cGMP decreased the pH level below the baseline after application of AVP, and an inhibition by ANP and cGMP of AVP-induced VSMC shape change was also observed. The recovery of cellular pH after three different types of acid load, namely, ammonium chloride pulse, nigericin clamp and lowering of extracellular pH, was significantly decreased by ANP and cGMP. Taken together, these results indicate that ANP/cGMP inhibit the activity of the Na+/H+ antiporter in VSMC, either in hormone- or pH-stimulated conditions.
Caramelo
C
C
Department of Medicine, University of Colorado School of Medicine, Denver.
López-Farré
A
A
Riesco
A
A
Olivera
A
A
Okada
K
K
Cragoe
E J
EJ
Tsai
P
P
Briner
V A
VA
Schrier
R W
RW
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000493:pharmacokinetics; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D028021:Sodium-Potassium-Chloride Symporters
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D001127:Arginine Vasopressin; D000584:Amiloride; D009320:Atrial Natriuretic Factor; D012964:Sodium; D006152:Cyclic GMP