saralasin and Alkalosis

Chloride-depletion alkalosis (CDA) has been characterized by hypereninemia. To determine whether angiotensin II (ANG II) has an important role in its maintenance or correction, anesthetized alkalotic rats, chloride depleted by peritoneal dialysis, were infused with 5% dextrose and saralasin (1 microgram.kg-1.min-1) (SAR) or vehicle (SAR-C), 5% dextrose and pretreatment with enalapril (1-1.5 mg/kg) (ENP) or vehicle (ENP-C), or 80 mM Cl solution with ANG II (20 micrograms/min) (ANG) or vehicle (ANG-C). Rats infused with 5% dextrose showed no differences in the magnitude of the alkalosis, inulin clearance, or urinary total CO2 excretion; both SAR and ENP were associated with decreased blood pressure. In SAR, tCO2 delivery out of late proximal convoluted tubule did not differ from that in SAR-C. Rats infused with 80 mM Cl corrected CDA similarly (delta plasma [Cl] - ANG-C + 6 +/- 1, ANG + 5 +/- 1 mM; P = not significant). These data suggest that, although ANG II can importantly influence vascular tone and early proximal tubule bicarbonate reabsorption, it does not have an important role in the renal maintenance or correction of acute CDA.

Topics: Alkalosis; Angiotensin II; Animals; Blood Pressure; Chlorides; Electrolytes; Enalapril; Male; Rats; Rats, Inbred Strains; Saralasin

Inhibition of angiotensin II activity reduces reabsorption of both bicarbonate and chloride predominantly in the S1 subsegment of the proximal convoluted tubule (PCT). Because the S2 PCT is intrinsically better able to compensate for the increased delivery of bicarbonate compared with chloride under normal conditions, we reasoned that angiotensin II inhibition might selectively raise the amount of sodium chloride emerging from the PCT. Free-flow micropuncture techniques were used in normal and alkalotic Munich-Wistar rats that were euvolemic or plasma volume depleted. In the normal volume-depleted animals, saralasin caused a small rise in single-nephron glomerular filtration rate (29.5 +/- 0.6 to 31.5 +/- 0.6 nl/min, P less than 0.025) and fall in bicarbonate and chloride reabsorption in the 1st mm (S1) PCT (387 +/- 22 to 348 +/- 23 peq.mm-1.min-1, P less than 0.05, and 341 +/- 27 to 217 +/- 57 peq.mm-1.min-1, P less than 0.05, respectively). Reabsorptive compensation by the S2 PCT maintained the end-PCT delivery of bicarbonate unchanged (76 +/- 4 to 78 +/- 3 peq.mm-1.min-1, NS), but end-PCT chloride delivery increased significantly (2,014 +/- 41 to 2,248 +/- 29 peq.mm-1.min-1, P less than 0.01). Early distal convoluted tubule (DCT) and urinary bicarbonate excretion were unchanged, but DCT chloride delivery increased associated with a chloruresis. When metabolic alkalosis was present, however, S2 compensation for increased bicarbonate delivery was attenuated so that end-PCT, DCT, and urinary bicarbonate as well as chloride delivery rates increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Alkalosis; Angiotensin II; Animals; Bicarbonates; Biological Transport; Hydrogen-Ion Concentration; Kidney Glomerulus; Kidney Tubules; Male; Rats; Rats, Inbred Strains; Saralasin; Sodium; Sodium Bicarbonate; Sodium Chloride; Water-Electrolyte Balance