Spontaneously hypertensive rats (SHR) have decreased paracellular fluid uptake from the proximal tubule (PT) that is corrected by AT-1 receptor inhibition.

SHR have decreased PT reabsorption of electrolytes and water. Ang II AT-1 receptor blockade corrects the tubular electrolyte and water handling, but the exact mechanism is presently unknown. Since a substantial part of the reabsorption in PT is going through the paracellular route, we investigated if SHR have altered paracellular fluid permeability, and if so, if this is related to Ang II-induced oxidative stress. PT permeability was measured by infusion of ¹⁴C-mannitol in PT in vivo. Fractional recovery of ¹⁴C was measured in the urine from the contralateral kidney (unifying excretion of reabsorbed matter). Groups (n=8) of SHR received vehicle, the AT-1 receptor antagonist candesartan or equal blood pressure lowering treatment (HHR) and were compared to corresponding Wistar Kyoto (WKY). The oxidative stress marker 8-isoprostane was measured in kidney tissue and plasma. SHR had lower leakage compared to WKY (7.9±1.2 vs. 11.9±0.6%), but increased plasma and kidney isoprostane levels. Both candesartan and HHR restored leakage in SHR (20.2±2.1 and 13.4±1.4%, respectively) and related to isoprostane levels. In conclusion, the paracellular permeability in PT is reduced by Ang II due to AT-1 receptor activation and engagement of oxidative stress that is also due to the increase in blood pressure. These findings display a novel mechanism for regulation of PT permeability, which gives an explanation for the reduced PT reabsorption in SHR. [ABSTRACT FROM AUTHOR]