Decreased sensitivity to renal interstitial hydrostatic pressure in dahl salt-sensitive rats1

Abstract

The ability of Dahl salt-sensitive (DS) rats to excrete a sodium load is significantly lower than Dahl salt-resistant (DR) rats. Because renal interstitial hydrostatic pressure (RIHP) is a major mediator of natriuresis in response to a sodium load, we proposed that the renal tubules of DS rats are less responsive to increases in RIHP than those of DR rats. To test this hypothesis, we determined the effect of direct increases in RIHP on renal excretory function in prehypertensive DS and DR rats. RIHP was directly increased by renal interstitial volume expansion via injection of 50 μL of a 2% albumin and saline solution into the renal interstitium through a chronically implanted renal interstitial catheter. RIHP, mean arterial pressure, glomerular filtration rate, urine flow rate, urinary sodium excretion, and fractional excretions of sodium, potassium, and lithium (an indicator of proximal tubule sodium handling) were measured before and after direct increases in RIHP in DS (n=8) and DR (n=8) rats. Baseline urine flow rate; urinary sodium excretion; fractional excretions of sodium, potassium, and lithium; RIHP; mean arterial pressure; and glomerular filtration rate were not different between DS and DR rats. Renal interstitial volume expansion in DS rats significantly increased RIHP (∆4.7±0.8 mm Hg), urine flow rate (∆14.5±3.4 μL/min), urinary sodium excretion (∆2.62±0.62 μmol/min), and fractional excretions of sodium (∆1.54±0.37%), potassium (∆17.84±2.90%), and lithium (∆19.68±3.52%). Renal interstitial volume expansion in DR rats also increased RIHP (∆5.3±0.6 mm Hg), urine flow rate (∆36.4±4.8 μL/min), urinary sodium excretion (∆6.23±0.69 μmol/min), and fractional excretions of sodium (∆3.56±0.46%), potassium (∆37.85±3.75%), and lithium (∆30.19±4.21%) significantly. Compared with DR rats, DS rats had significantly smaller increases in urine flow rate, urinary sodium excretion, and fractional excretions of sodium, potassium, and lithium in response to equivalent increases of RIHP. These data demonstrate that despite similar mean arterial pressure and glomerular filtration rate DS rats have smaller proximal tubule and whole-kidney natriuretic responses to direct increases in RIHP and that this defect is present before the development of hypertension. These results suggest that a reduced sensitivity of renal tubules to increases in RIHP in prehypertensive DS rats may contribute to their inability to excrete a sodium load. © 1994 American Heart Association, Inc.