Early altered renal sodium handling determined by lithium clearance in spontaneously hypertensive rats (SHR): Role of renal nerves

The mechanism by which blood pressure rises in the SHR strain remains to be elucidated. Since the long-term changes in renal sodium tubule handling associated with genetic hypertension have not been examined in detail, we hypothesized that SHR hypertension development may result from sustained renal sympathetic nerve overactivity and consequently decreased urinary sodium excretion. To test this hypothesis, we assessed renal sodium handling and cumulative sodium balance for 10 consecutive weeks in unanesthetized renal-denervated SHR, performed prior to the start of the entire 10-week metabolic studies, and their age-matched normotensive and hypertensive controls. The present investigation shows that SHR excreted less sodium than Wistar-Kyoto (NNXy) rats during the initial 3-week observation period (p < 0.05). This tendency was reversed when SHR were 10-wk old. Fractional urinary sodium excretion (FENa+) was significantly lower in 3 and 6-wk-old SHR when compared with the WKy age-matched group, as follows: SHR3-wk-old: 0.33 +/- 0.09% and WKY3-wk-old: 0.75 +/- 0.1% (P < 0.05); SHR6-wk-old: 0.52 +/- 0.12% and WKY6-wk-old: 0.83 0.11%. The decreased FENa+ in young SHR was accompanied by a significant increase in proximal sodium reabsorption (FEPNa+) compared with the normotensive age-matched control group (P < 0.01). This increase occurred despite unchanged creatinine clearance (M) and fractional post-proximal sodium excretion (FEPPNa+)in all groups studied. The decreased urinary sodium excretion response in SHR up to the age of 6 weeks was significantly eradicated by bilateral renal denervation of SHR3-wk-old: 0.33 +/- 0.09% and SHR6-wk-old: 0.52 +/- 0.12% to DxSHR(3-wk-old): 1.02 +/- 0.2% and DxSHR(6-wk-old): 0.94 +/- 0.2% (P < 0.01), in renal denervated rats. The current data suggest that neural pathways may play an instrumental role on renal sodium reabsorption as result of sustained sympathetic nervous system overexcitability. (C) 2004 Elsevier Inc. All rights reserved.