Parallel adaptation of the rabbit renal cortical sodium/proton antiporter and sodium/bicarbonate cotransporter in metabolic acidosis and alkalosis.

Recent studies have shown that the bicarbonate reabsorptive capacity of the proximal tubule is increased in metabolic acidosis. For net bicarbonate reabsorption to be regulated, there may be changes in the rate of apical H+ secretion as well as in the basolateral base exit step. The present studies examined the rate of Na+/H+ exchange (acridine orange method) and Na+/HCO3 cotransport (22Na uptake) in apical and basolateral membranes prepared from the rabbit renal cortex by sucrose density gradient centrifugation. NH4Cl loading was used to produce acidosis (arterial pH, 7.27 +/- 0.03), and Cl-deficient diet with furosemide was used to produce alkalosis (arterial pH, 7.51 +/- 0.02). Maximal transport rate (Vmax) of Na+/H+ antiporter and Na+/HCO3 cotransporter were inversely related with plasma bicarbonate concentration from 6 to 39 mM. Furthermore, the maximal transport rates of both systems varied in parallel; when Vmax for the Na+/HCO3 cotransporter was plotted against Vmax for the Na+/H+ antiporter for each of the 24 groups of rabbits, the regression coefficient (r) was 0.648 (P less than 0.001). There was no effect of acidosis or alkalosis on affinity for Na+ of either transporter. We conclude that both apical and basolateral H+/HCO3 transporters adapt during acid-base disturbances, and that the maximal transport rates of both systems vary in parallel during such acid-base perturbations.

N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, amiloride analogues, and renal Na+/H+ antiporter.

N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) is a carboxyl-activating agent and has been shown to inhibit the renal Na+/H+ antiporter. The purposes of the present studies were to characterize the kinetics of inhibition of the Na+/H+ antiporter by EEDQ and to determine whether amiloride analogues affect the ability of EEDQ to inhibit the rate of Na+/H+ exchange. Brush-border membrane vesicles (BBMV) were prepared from rabbit kidneys; Na+/H+ exchange rate was assessed by the fluorescence quenching of acridine orange. EEDQ produced a concentration-dependent inhibition of Na+/H+ exchange; the effect was to decrease the maximum activity (Vmax) from 5.51 to 2.03 fluorescence units X mg protein-1 X S-1) and Km (from 14.1 to 8.7 mM) compared with control BBMV. Pretreatment of BBMV with amiloride before the addition of EEDQ maintained both Vmax and Km at values that were not significantly different from those for control BBMV. Compared with a series of analogues, amiloride was only the third most potent inhibitor of the rabbit renal Na+/H+ antiporter; amiloride, however, provided the greatest protection against inhibition of the antiporter by the subsequent addition of EEDQ. These findings suggest that the 2-carbonylguanidininum moiety and 6-chloro atom are important for binding of amiloride to sites at or near the antiporter; the group at position 5 is important in determining the ability of amiloride to protect against inhibition of the Na+/H+ antiporter by EEDQ. Finally, the ability of amiloride to protect against inactivation of the renal Na+/H+ antiporter by EEDQ is reversible.

Cirrhotic ascites. Pathophysiology, diagnosis, and management.

Cirrhotic ascites occurs via both overflow and underfill mechanisms. Intrahepatic hypertension activates a hepatic baroreceptor reflex that enhances renal sodium absorption; plasma volume is expanded. As cirrhosis progresses, the hepatoportal Starling forces become sufficiently disturbed to sequester this "overflow" in the peritoneal cavity, which results in ascites formation. "Underfill" of the vascular system occurs and eventually dominates the clinical picture. Finally, intrahepatic hypertension also activates the renin-angiotensin system, which causes renal vasoconstriction; the increase in renal prostaglandin synthesis maintains renal blood flow. Although cirrhotic ascites is traditionally classified as a transudate, the serum-ascites albumin gradient may be a better indicator of ascites secondary to portal hypertension than other causes. General management of patients with cirrhotic ascites includes severe restriction of dietary sodium intake and bed rest; diuretics are added if spontaneous diuresis does not occur after 3 to 4 days.

Cat scratch disease. Report of a case with hepatic lesions and a brief review of the literature.

An unusual case of cat scratch disease with large hepatic defects is presented. We describe a previously healthy 16-yr-old black man presenting with a neck mass, hepatosplenomegaly, and systemic symptoms. Pathology of the neck mass revealed a lymph node with chronic inflammation and focal necrosis. An abnormal computed tomography scan showed large hepatic defects which were confirmed at peritoneoscopy; biopsy specimens are described. Routine and special stains for bacteria and fungi were all negative. Serologic studies were unremarkable but a cat scratch skin test was positive. Follow-up examinations revealed resolution of all findings. Cat scratch disease should be considered in the differential diagnosis of diseases causing lymphadenopathy, systemic symptoms, and hepatic (and splenic) defects.

Lack of effect of prostaglandin inhibition on calcium excretion in normal volunteers.

Recent data have shown that administration of indomethacin to patients with hypercalciuric nephrolithiasis decreased urinary calcium excretion, implying a possible pathogenic role for renal prostaglandins in hypercalciuria. To explore this hypothesis we administered indomethacin, ketoprofen and aspirin to normal volunteers for 6 days and assessed daily creatinine clearance and urinary excretion of sodium and calcium. In contrast to previous studies, subjects were maintained on a constant metabolic diet. These nonsteroidal anti-inflammatory drugs decreased urinary sodium excretion but had no effect on creatinine clearance or urinary calcium excretion. In summary, our data do not support an important physiologic role of renal prostaglandins in renal calcium excretion in normal subjects.