DUAL MODULATION OF NA H ANTIPORT BY ATRIAL-NATRIURETIC-FACTOR IN RAT AORTIC SMOOTH-MUSCLE CELLS/

The aim of the present work was to study the effect of the atrial natr iuretic factor (ANF) on the Na/H antiport in rat aorta smooth muscle c ells, evaluated as intracellular pH (pH(i)) recovery after an acid loa d with ammonium chloride. The Na/H antiport was studied using a fluore scent probe, sensitive to pH(i), 2',7'-bis(carboxyethyl)-5(6)-carboxyf luorescein. Our data indicate that ANF modulates the activity of the N a/H antiport in both a dose- and time-dependent manner. Hormone concen trations of 10(-10) M activate the antiport, increasing both the rate of recovery and the set point by similar to 0.2 pH units. This effect is mediated by diacylglycerol as a result of phospholipid hydrolysis b y a phospholipase C, even if an involvement of adenosine 3',5'-cyclic monophosphate (cAMP) cannot be ruled out. ANF (10(-7) M) inhibits the antiport, decreasing both the rate of recovery and the set point by si milar to 0.3 pH units, because of guanosine 3',5'-cyclic monophosphate production. Both inhibition and stimulation of pH(i) by ANF were more pronounced when the hormone was given before the acid load, perhaps b ecause of the longer time exposure. We present new hypotheses on the m echanism of action of this paracrine/autocrine factor.