DECREASED SENSITIVITY TO RENAL INTERSTITIAL HYDROSTATIC-PRESSURE IN DAHL SALT-SENSITIVE RATS

The ability of Dahl salt-sensitive (DS) rats to excrete a sodium load is significantly lower than Dahl salt-resistant (DR) rats. Because ren al interstitial hydrostatic pressure (RIHP) is a major mediator of nat riuresis in response to a sodium load, we proposed that the renal tubu les 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 i ncreases in RIHP on renal excretory function in prehypertensive DS and DR rats. RIHP was directly increased by renal interstitial volume exp ansion via injection of 50 mu L of a 2% albumin and saline solution in to the renal interstitium through a chronically implanted renal inters titial catheter. RIHP, mean arterial pressure, glomerular filtration r ate, urine flow rate, urinary sodium excretion, and fractional excreti ons of sodium, potassium, and lithium (an indicator of proximal tubule sodium handling) were measured before and after direct increases in R IHP in DS (n = 8) and DR (n = 8) rats. Baseline urine flow rate; urina ry sodium excretion; fractional excretions of sodium, potassium, and l ithium; RIHP; mean arterial pressure; and glomerular filtration rate w ere not different between DS and DR rats. Renal interstitial volume ex pansion in DS rats significantly increased RIW (Delta 4.7+/-0.8 mm Hg) , urine flow rate (Delta 14.5+/-3.4 mu L/min), urinary sodium excretio n (Delta 2.62+/-0.62 mu mol/min), and fractional excretions of sodium (Delta 1.54+/-0.37%), potassium (Delta 17.84+/-2.90%), and lithium (De lta 19.68+/-3.52%). Renal interstitial volume expansion in DR rats als o increased RIHP (Delta 5.3+/-0.6 mm Hg), urine flow rate (Delta 36.4/-4.8 mu L/min), urinary sodium excretion (Delta 6.23+/-0.69 mu mol/mi n), and fractional excretions of sodium (Delta 3.56+/-0.46%), potassiu m (Delta 37.85+/-3.75%), and lithium (Delta 30.19+/-4.21%) significant ly. Compared with DR rats, DS rats had significantly smaller increases in urine flow rate, urinary sodium excretion, and fractional excretio ns of sodium, potassium, and lithium in response to equivalent increas es 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 R IHP and that this defect is present before the development of hyperten sion. These results suggest that a reduced sensitivity of renal tubule s to increases in RIHP in prehypertensive DS rats may contribute to th eir inability to excrete a sodium load.