Abstract 075: The Kidney-OVLT Neuroaxis Mediates Neurogenic Hypertension And Polydipsia In 2-Kidney, 1-Clip Rats

Abstract

Renal afferent nerves mediate activation of the sympathetic nervous system and hypertension in rats with unilateral renal artery stenosis (2K1C-HTN). However, the central neural structures that mediate this response are unclear. The organum vasculosum of the lamina terminalis (OVLT), has also been implicated in the regulation of mean arterial pressure (MAP) and sympathetic activity in preclinical models of hypertension. We tested the hypothesis that afferent renal nerves and the OVLT share a common neural pathway required for the development of 2K1C-HTN. Two experiments were conducted. 1: Male rats (n=5-9) were implanted with telemeters to measure MAP. 1-week later they received a clip on the left renal artery and were subjected to afferent renal denervation (ARDN) by periaxonal capsaicin (2K1C-ARDN) or sham (2K1C-sham) treatment of the clipped kidney. 2: Male rats (n=6-8) were subjected to lesioning of the OVLT (OVLTx) or sham operation. 1-week later telemeters were implanted and 7 days later the left renal artery was stenosed by application of a silver clip. In both experiments, MAP was measured continuously for 6 weeks, and water intake (WI) was measured once a week. Neurogenic pressor activity (NPA) was assessed by measuring the peak MAP response to ganglionic blockade. EXPT 1 Results: At the end of the protocol, MAP was 165±5 mmHg in 2K1C-sham compared to 131±10mmHg in 2K-1C-ARDN rats (p<0.001). WI increased in 2K1C-sham rats peaking at 110±13 ml/day at week 2. In contrast, WI was markedly reduced in 2K1C-ARDN rats at this same time point (41±3 ml/day). NPA was increased in 2K1C-sham (-50 ± 4 mmHg) but was reduced in 2K1C-ARDN (-25 ± 3 mmHg) rats (p<0.05). EXPT 2 Results: At end of the protocol MAP was 162±6 mmHg in sham-2K1C rats compared to 135±8 mmHg in OVLTx-2K1C rats (p<0.001). WI peaked at 74±9 ml/day in sham lesion-2K1C compared to 52±9 ml/day in OVLTx-2K1C rats at week 2 (p<0.05). NPA was increased in sham-2K1C rats (-51 ± 3 mmHg) but was reduced in OVLTx-2K1C rats (-31 ± 4 mmHg) (p<0.05). Since both ARDN and OVLTx attenuated MAP, WI, and NPA similarly in 2K1C rats, we hypothesize that afferent renal nerves and the OVLT are linked in a common neural pathway required for the development of hypertension following renal artery stenosis.