Hemodynamic mechanisms of renal injury in Dahl SS rats fed a high salt diet

Abstract

Theextent to which hypertensive renal injury in Dahl salt‐sensitive (SS) rats is dependent on the hemodynamic effects of increased NaCl intake in addition to elevated blood pressure (BP) remains uncertain. In the present study, we assessed BP (radiotelemetry), protein uria and glomerulosclerosis (GS) indifferent groups of male Dahl SS rats (Harlan) fed a 1% (n=8), 2% (n=12), or 4%(n=12) NaCl diet for 4 weeks. Progressive increases in NaCl intake led to progressive and significant (P<0.05) increases in BP (150±4, 163±3, 173±2 mmHg). A similar pattern was observed with respect to protein uria (69±13, 86±10, 104±9mg/day) and GS (6±1, 14±2, 17±1 %) in rats fed a 1%, 2%, and 4% NaCl diet, respectively. A significant (P<0.0001) correlation between BP and GS(y=1.6x‐173, r2=0.39) and a relatively low BP threshold for the development of GS (~155 mmHg) was evident in this model. Of interest, hypertensive vascular injury was not observed, indicating that the increased susceptibility to hypertensive injury is primarily manifested at the level of the glomerular capillaries at least with this severity of hypertension. An additional group of SS rats (n=8) administered a 4% NaCl diet for 4 weeks were also administered hydralazine(100–200 mg/L in the drinking water) to prevent NaCl‐induced increases in BP. A significantly lower BP (139±3 mmHg) and tendency for a lower GS (10±2 %, P=0.07) was observed in rats fed a 4% NaCl diet+ hydralazine vs. rats fed a 4% NaCl diet, suggesting that glomerular injury in this model is in part dependent on elevated BP. However, despite a significantly lower BP as compared to rats fed a 1% NaCl diet, GS tended (P=0.07)to be higher in rats administered a 4% NaCl diet + hydralazine, suggesting that elevated NaCl intake, per se, may also promote renal injury in this model. We therefore evaluated mean arterial pressure (MAP, radiotelemetry) ‐renal blood flow (RBF, Transonic) relationships before and 3–5 days after 4% NaCl diet administration in an additional group of conscious, chronically instrumented SS rats (n=7). Despitea similar MAP at baseline and during 4% NaCl administration (131±2 vs. 132±3mmHg, respectively), a significant 19% decrease in ambient renal vascular tone(i.e., decreased renal vascular resistance) and 27% increase in RBF was noted during 4% NaCl administration. To determine whether such effects of increased NaClintake, per se, on renal vascular function were mediated via an impairment inrenal auto regulation, we assessed renal auto regulatory responses (changes in RBF during spontaneous changes in BP of 5 mmHg or greater) in conscious, chronically instrumented rats using recently developed novel methodologies. No differences in renal auto regulatory responses were observed at baseline vs. during 4% NaClintake. In summary, the results indicate that the renal injury that develops in Dahl SS rats fed a 4% NaCl diet is dependent upon both elevated BP and the hemodynamic effects of increased NaCl intake that are expected to increase the transmission of systemic BP to the renal microvasculature. These data however do not exclude the possibility of a contribution of adverse hemodynamic effects of hydralazine, per se, to enhance renal BP transmission during increased NaCl intake.Support or Funding InformationVeterans Administration, NIH