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 inhibi tory effect of atrial natriuretic peptide (ANP) on the sustained contr action phase of vascular smooth muscle cells (VSMC). Specifically, the potential role of ANP on the Na+/H+ antiporter and Na+ transport syst ems was investigated. Both ANP and 8-bromo cGMP inhibited Na-22+ uptak e and decreased intracellular Na ([Na+]i) in VSMC, an effect that was mimicked by the specific Na+/H+ antiporter inhibitor, hexamethylen ami loride (HMA). The effect of ANP was not additive with HMA, therefore s uggesting that both inhibit the same Na-22+ transport pathway. On the other hand, the inhibition of Na-22+ 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 me dium, ANP, cGMP, and HMA significantly inhibited the AVP-induced intra cellular alkalinization, an effect which was associated with significa nt 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 V SMC shape change was also observed. The recovery of cellular pH after three different types of acid load, namely, ammonium chloride pulse, n igericin clamp and lowering of extracellular pH, was significantly dec reased by ANP and cGMP. Taken together, these results indicate that AN P/cGMP inhibit the activity of the Na+/H+ antiporter in VSMC, either i n hormone- or pH-stimulated conditions.