The role of catecholamines in regulation of renal tubular sodium transport

Renal sodium metabolism, a major determinant of arterial blood pressure, is regulated with remarkable precision by a variety of endocrine, autocrine and neuronal factors. All these factors are known to regulate sodium metabolism by affecting the rate of renal tubular sodium reabsorption. The transport of sodium across the renal tubular cell occurs by apical Na+ transporters and basolaterally located Na+, K+-ATPase. The aim of the present study was to examine the mechanisms whereby well-established antinatriuretic and natriuretic factors regulate renal tubular sodium reabsorptionin rats. The activities of apical Na+ transporters were measured by a rapid filtration technique in brush border membrane vesicles, prepared by differential centrifugations and Mg2+-precipitation techniques. Na+, K+-ATPase activity was measured as ouabain-sensitive ATP hydrolysis in microdissected proximal tubular segments (PCT) from collagenase treated kidneys. High salt (HS) diet decreases PCT Na+, K+-ATPase activity. In contrast we found that HS diet did not induce any adaptive changes in the activities of the major Na+transporters located in the apical cell membrane. Na+, K+-ATPase was found to be a direct target for first messengers involved in the regulation of renal tubular sodium reabsorption. The stimulatory effect of antinatriuretic factors (alpha-adrenoceptoragonist and angiotensin II) was counteracted by the inhibitory effect of natriureticfactors (ß-adrenoceptor agonist, dopamine, and atrial natriuretic peptide) via a common intracellular pathway where the ultimate step is a reversible phosphorylation of Na+, K+-ATPase. Procedures aimed at increasing intrarenal dopamine availability induced dopamine-dependent natriures is which was associated with decreased Na+, K+-ATPase activity. Norepinephrine increased Na+, K+-ATPase activity only in the presence of its co-transmitter neuropeptide Y or in the presence of a ß-adrenoceptor antagonist. The nephrotoxic drug, FK 506, decreased Na+, K+-ATPase activity via stimulation of ß-adrenoceptors. Treatment with a ß-adrenoceptor antagonist protected against the renal effects of FK 506. In conclusion, this study shows that catecholamines are important regulators of renal sodium metabolism. Na+, K+-ATPase is the common final effector on which antinatriuretic and natriuretic factors act to regulate urinary sodium excretion. Knowledge of the intracellular signaling pathways used by these factors and how the availability and effects of these factors are regulated is needed to better understand the pathogenesis of hypertension