Abstract P018: Periodic Water Intake Exacerbates Hypertension, Decreases Renal Function and Increases Renal Inflammation in Spontaneously Hypertensive Rats

Abstract

Water is essential for life. The kidneys are major regulators of fluid balance but also appear susceptible to adverse effects of periodic water intake since epidemiological studies have linked low water intake to chronic kidney disease. However, the impact of periodic water intake on renal health has largely been ignored. This study investigated the chronic effects of periodic drinking on blood pressure, kidney function, and immune cell infiltration in rats with pre-existing hypertension. Mean arterial pressure (MAP) was measured continuously in spontaneously hypertensive rats (SHR) that were only given access to water for 2 hours per day versus control rats given free access to water over a 4-week period (n=>8 per group). Glomerular filtration rate (GFR) was measured via transcutaneous FITC-sinistrin clearance at baseline and at the end of the 4-week protocol. Renal immune cell infiltration and cytokine production was assessed by flow cytometry. Basal MAP and renal function were similar between the control and water-restricted (WR) groups. Water restriction led to a significant increase in MAP from baseline (8.8±4.5mmHg versus 0.6±5.5mmHg in WR and control SHR, respectively; P<0.05). Moreover, GFR decreased from baseline by 29±6% in the WR SHR (P<0.001). In comparison, GFR did not change significantly over time in the control SHR (-5.3±2.6% from baseline; P>0.05). The increase in MAP and reduction in renal function in the WR-SHR was associated with periodic increases in urine osmolality (69±26% versus baseline, P<0.05), indicative of cycles of dehydration and replenishment. Renal immune cell infiltration was similar between the groups. However, cytokine analyses revealed a phenotypic shift towards a pro-inflammatory Th1 phenotype in kidney T cell infiltrate from WR versus control SHR. This was indicated by a greater proportion of T cells producing IFN-γ in SHR subjected to water restriction than control SHR (9.5±3.3% versus 2.9±0.9%, respectively; P<0.05). In conclusion, recurrent dehydration associated with periodic drinking exacerbates hypertension, renal dysfunction and inflammation in male SHR. This highlights the importance of regular water intake for the maintenance of kidney health, particularly in populations with existing disease.