Despite structural narrowing of the renal afferent arterioles (Ledingham et al. 1998), adult genetically hypertensive (GH) rats have been shown to have lower extracellular fluid volume and total body sodium similar to that of control normotensive (N) rats (Gresson et al. 1973). This normalisation of body fluid status may reflect renal compensation in the face of chronic exposure to high blood pressure. Accordingly, the aim of this study was to compare renal function in young and adult GH rats.
Standard renal clearance techniques were used to assess renal function in pentobarbitone-anaesthetised N and GH rats at the age of 5-6 weeks (N n = 9, GH n = 5) and 19-20 weeks (N n = 6, GH n = 5). Saline at 0.9 % containing inulin and para-aminohippuric acid was infused at 50 µl min-1 (100 g body wt)-1 in young rats and 100 µl min-1 in adult rats for 3 and 6 h, respectively. Clearance measurements were made over the final hour in young rats and over 3 h in the adult rats. Animals were humanely killed at the end of the experiment.
Blood pressure was significantly higher in both young (N 101 ± 6 vs. GH 125 ± 9 mmHg, Student’s unpaired t test, P < 0.05) and adult GH rats (N 103 ± 7 vs. GH 149 ± 12 mmHg, P < 0.01). Young GH rats had significantly lower (P < 0.05) effective renal blood flow, glomerular filtration rate, urine flow rate and sodium excretion than N rats (Table 1). These differences were no longer apparent in adult rats.
Renal function is impaired in young but not adult GH rats. These data suggest that a shift in the pressure-natriuresis relationship occurs as the GH rat matures, resulting in the restoration of renal function at the expense of an increase in systemic blood pressure. Thus, impaired renal function may underlie the development of hypertension in the GH rat.
This work was supported by a Wellcome Trust Travel Award.