Abstract 334: Selective Renal Deafferentation Attenuates the Development of Genetic and Renal Hypertension

Abstract

Renal denervation decreases arterial pressure (AP) in hypertensive rats and humans. This procedure destroys both afferent and efferent nerves. Several investigators have proposed that renal afferent nerves contribute to the elevated AP. We developed a procedure to selectively remove renal afferent nerves with capsaicin (1-100 mM) both topically on the nerve and in the renal pelvis. We examined the effects of renal deafferentation on the development of genetic and renal hypertension. We studied spontaneously hypertensive rats (SHR), and a model of renal hypertension, two kidney-one clip (2K1C) in Sprague-Dawley rats. SHR were treated at 3-4 weeks of age with capsaicin. Mean arterial pressure was recorded by tail cuff through 16 weeks of age. On week 17, rats were cannulated, allowed 3 days to recover then had their AP measured directly for 3 days (3 hrs/day). Rats with renal deafferentation (n=11) had lower arterial pressure weeks 9-16 (average reduction AP=10.1±1.4 mmHg, ANOVA, p=0.0049) compared to control (saline treated, n=6) although the final direct recording was not significantly different on week 17 (control AP=184.1±3.4 mmHg vs deafferented AP=173.9±4.3 mmHg, p=0.07). Substance P levels from the kidneys were reduced in deafferented rats compared to control (6.9±1.0 vs 17.3±5.2 pg/g protein, p=0.0009). In contrast, renal NE levels were not altered (307±19 vs 313±20 pg/g protein, p=0.428). In the second study, the left kidney in weanling Sprague-Dawley rats was exposed to capsaicin or saline. Rats were allowed to mature (>250 g BW) then subjected to left renal artery clipping (0.2mm) or sham clip. AP was recorded by tail cuff during development of 2K1C for 6 weeks before direct cannulation to record AP on week 7. Renal deafferentation prevented the development of hypertension in 13 rats compared to 9 saline treated rats (average reduction AP=16.9±2.7 mmHg, ANOVA, p=0.0031). Saline treated rats had a higher AP 7 weeks after clipping (147.1±10.2 vs 130.5±4.2 mmHg direct recording, p=0.02). The left kidney contained 48% SP compared to the right kidney (p=0.04). These data suggest that increased afferent renal nerve activity contributes to the elevation in AP in hypertension and contributes to essential hypertension in humans. Supported by USPHS DA017371.