Blood pressure and tubuloglomerular feedback mechanism in chronically salt-loaded spontaneously hypertensive rats

Blood pressure and tubuloglomerular feedback mechanism in chronically salt-loaded spontaneously hypertensive rats. Experiments were performed to qualitatively characterize the effects of tubuloglomerular feedback (TGF) inhibition by chronic salt loading on salt sensitivity of blood pressure in spontaneously hypertensive rats (SHR). After two weeks of salt loading, systolic blood pressure (SBP) was significantly exacerbated and plasma volume (PV) was expanded in salt-loaded SHR compared with those in control SHR (SBP: 182 ± 1 vs. 159 ± 2mm Hg; PV: 4.38 ± 0.06 vs. 4.04 ± 0.03 ml/100 g body wt, respectively). Plasma volume of WKY was also but only transiently expanded by salt loading, whereas plasma volume expansion in SHR had persisted over the entire dietary treatment period. TGF activity was assessed as the maximal reduction of single nephron GFR (SNGFR) on increasing loop of Henle perfusion rate from 0 to 40 nl/min using previously collected tubular fluid from salt-loaded rats (TFs) or control rats (TFc). Maximal TGF response in salt-loaded SHR with TFs was 14.9 ± 2.9% and 57.8 ± 2.6% with TFc. In control SHR the responses were 16.9 ± 2.5% with TFs and 52.7 ± 2.9% with TFc. In salt-loaded WKY the response with TFs were 3.1 ± 1.6% and 37.4 ± 2.8% with TFc. And in control WKY, the response with TFs were 8.2 ± 1.9% and 40.8 ± 2.8% with TFc, respectively. These results indicate the TGF resetting in chronically salt-loaded SHR and WKY is caused by the activation of humoral TGF inhibitory factor. The suppression of TGF in SHR was, however, far more variable and, on average, less than in WKY. In addition, the maximum TGF response elicited by TFs in SHR and systolic blood pressure in conscious donor SHR were significantly correlated (r= 0.8142). This indicates that in salt-loaded SHR less activation of the TGF inhibitory factor goes in hand with a greater blood pressure increase. It is thus reasonable to propose that the renal response to chronic salt-loading in SHR might be blunted by defective activation of the feedback inhibitory substance. This defect may contribute to the exacerbation and maintenance of hypertension in this strain