We have reported that the natriuresis induced by CCBs is mediated by their interaction with renal D1-like dopamine receptors (Am J Physiol 267:F965, 1994). Renal D1-like receptors produce a natriuresis by inhibition of both luminal sodium/hydrogen exchange (NHE) and basolateral Na+/K+ATPase activities. Whether CCBs produce a natriuresis by similar mechanisms is not known. We, therefore, measured NHE activity in renal brush border membrane vesicles (BBMV) by the 3″ N-methyl-N-isobutyl amiloride (100 μM) sensitive uptake of 22Na; the ouabain (2 mM)-sensitive dephosphorylation of (Tris)-p-nitrophenylphosphate by K+-p-nitrophenylphosphatase was used as the index of Na+/K+ATPase activity. The CCB, diltiazem (10 μg/kg/min) was infused into the right renal artery of anesthetized rats. After 80 min (time needed for maximal diuresis), the infused right and non-infused left (control) kidneys were analyzed. D1 receptor-mediated inhibition of renal proximal tubular NHE and outer medullary Na+/K+ATPase activity is via protein kinase A (PKA) activation. However, diltiazem did not affect NHE activity in BBMV (control = 1.29 ± 0.44, n = 3, diltiazem = 1.24± 0.39 nmol/mg protein/min) or PKA activity in renal cortical tubules(n = 4). Diltiazem also did not affect Na+/K+ATPase activity of tubular suspensions from the inner stripe of the outer medulla (n = 8). However, the diltiazem-induced natriuresis (up to-fold, without hemodynamic changes) was significantly correlated with the inhibition (34 ± 7%) of renal cortical tubular Na+/K+ATPase activity (r = 0.87, p<0.01, n = 8). Thus, diltiazem appears to induce a natriuresis by inhibition of Na+/K+ATPase activity in renal cortex. Since the dopamine-mediated inhibition of renal cortical tubular Na+/K+ATPase activity is due to PKC, it is possible that CCB/D1 receptor interaction occurs at this level.
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Albrecht, F., Asico, L., Jose, P. et al. MECHANISM OF CALCIUM CHANNEL BLOCKER (CCB)-MEDIATED NATRIURESIS. † 2126. Pediatr Res 39 (Suppl 4), 357 (1996). https://doi.org/10.1203/00006450-199604001-02150
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DOI: https://doi.org/10.1203/00006450-199604001-02150