The role of catecholamines in regulation of renal tubular sodium transport

Abstract: The role of catecholamines in regulation of renal tubular sodiumtransport Ulla Holtbäck Renal sodium metabolism, a major determinant of arterial blood pressure, is regulatedwith remarkable precision by a variety of endocrine, autocrine and neuronal factors.All these factors are known to regulate sodium metabolism by affecting the rate ofrenal tubular sodium reabsorption. The transport of sodium across the renal tubularcell occurs by apical Na+ transporters and basolaterally located Na+, K+-ATPase. The aim of the present study was to examine the mechanisms whereby well-establishedantinatriuretic and natriuretic factors regulate renal tubular sodium reabsorptionin rats. The activities of apical Na+ transporters were measured by a rapid filtrationtechnique in brush border membrane vesicles, prepared by differential centrifugationsand Mg2+-precipitation techniques. Na+, K+-ATPase activity was measured as ouabain-sensitiveATP hydrolysis in microdissected proximal tubular segments (PCT) from collagenasetreated kidneys. High salt (HS) diet decreases PCT Na+, K+-ATPase activity. In contrast we foundthat 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 bea direct target for first messengers involved in the regulation of renal tubularsodium 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) viaa common intracellular pathway where the ultimate step is a reversible phosphorylationof Na+, K+-ATPase. Procedures aimed at increasing intrarenal dopamine availabilityinduced dopamine-dependent natriuresis which was associated with decreased Na+, K+-ATPaseactivity. Norepinephrine increased Na+, K+-ATPase activity only in the presence ofits 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 ofß-adrenoceptors. Treatment with a ß-adrenoceptor antagonist protected againstthe renal effects of FK 506. In conclusion, this study shows that catecholamines are important regulators ofrenal sodium metabolism. Na+, K+-ATPase is the common final effector on which antinatriureticand natriuretic factors act to regulate urinary sodium excretion. Knowledge of theintracellular signaling pathways used by these factors and how the availability andeffects of these factors are regulated is needed to better understand the pathogenesisof hypertension. Key words: sodium balance, Na+, H+-antiporter, Na+, K+-ATPase, renal proximaltubules, hormonal regulation. ISBN 91-628-2854-1, Stockholm 1998