Reversal of Genetic Salt-Sensitive Hypertension by Targeted Sympathetic Ablation

Hypertension - Tập 61 Số 4 - Trang 806-811 - 2013
Jason D. Foss1,2, Gregory D. Fink1,2, John W. Osborn1,2
1From the Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN (J.D.F., J.W.O.); and the Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI (G.D.F.).
2the Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI (G.D.F.).

Tóm tắt

The sympathetic nervous system plays an important role in some forms of human hypertension as well as the Dahl salt-sensitive rat model of hypertension; however, the sympathetic targets involved remain unclear. To address this, we examined the role of the renal and splanchnic sympathetic nerves in Dahl hypertension by performing sham surgery (n=10) or targeted sympathetic ablation of the renal nerves (renal denervation, n=11), the splanchnic nerves (celiac ganglionectomy, n=11), or both renal and splanchnic nerves (n=11) in hypertensive Dahl rats. Mean arterial pressure increased from ≈120 mm Hg, while on a 0.1% sodium chloride diet, to ≈140 mm Hg after being fed a 4.0% sodium chloride diet for 3 weeks. At that point, rats underwent sham or targeted sympathetic ablation. Four weeks after treatment, mean arterial pressure was lower in renal denervated (150.4±10.4) and celiac ganglionectomized (147.0±6.1) rats compared with sham rats (165.0±3.7) and even lower in rats that underwent both ablations (128.4±6.6). There were no differences in heart rate or fluid balance between sham and renal denervated rats; however, rats that underwent either celiac ganglionectomy or both ablations exhibited marked tachycardia as well as sodium and water retention after treatment. These data suggest that targeted sympathetic ablation is an effective treatment for established hypertension in the Dahl rat and that the kidneys and the splanchnic vascular bed are both independently important targets of the sympathetic nervous system in this model.

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Tài liệu tham khảo

10.1016/S0140-6736(06)68770-9

10.1161/hypertensionaha.111.170308

10.1161/CIRCULATIONAHA.111.030189

10.1161/01.hyp.0000252676.46043.18

10.1111/j.1524-6175.2002.02045.x

10.1016/S0140-6736(10)62039-9

10.1161/HYPERTENSIONAHA.110.163014

10.1016/S0140-6736(09)60566-3

10.1152/ajplegacy.1953.174.3.397

10.1001/jama.1953.03690160001001

10.1097/00000658-195310000-00006

10.1161/hypertensionaha.107.090696

Takeshita A, Mark AL, Brody MJ. Prevention of salt-induced hypertension in the Dahl strain by 6-hydroxydopamine. Am J Physiol. 1979;236:H48–H52.

10.3109/10641967909068639

10.1042/cs061053s

10.1161/01.HYP.3.3_Pt_2.I135

10.1161/01.hyp.17.1_suppl.i86

10.1152/physiolgenomics.00027.2010

Boegehold MA, Huffman LJ, Hedge GA. Peripheral vascular resistance and regional blood flows in hypertensive Dahl rats. Am J Physiol. 1991;261(4 pt 2):R934–R938.

10.1161/01.HYP.11.6.523

10.1139/y87-385

Iwata T, Muneta S, Kitami Y, Okura T, Ii Y, Murakami E, Hiwada K. Effect of renal denervation on the development of hypertension in Dahl-Iwai salt-sensitive rats. Nihon Jinzo Gakkai Shi. 1991;33:867–871.

10.1093/ndt/gfq139

10.1152/ajpregu.00371.2010

10.1152/ajpheart.01029.2002

10.1016/j.autneu.2009.11.009

10.1113/expphysiol.2007.039545

10.1152/physrev.00007.2009

10.1038/nrn1902

10.1152/ajpregu.00647.2009

10.1111/j.1440-1681.2005.04179.x

10.1161/HYPERTENSIONAHA.112.193870

10.1038/ki.1988.120

10.1152/ajpregu.90650.2008

10.1161/01.hyp.0000160404.08866.5a

10.1056/NEJM199212313272704

10.1161/01.CIR.0000034043.16664.96

10.1113/jphysiol.2012.228619

10.1152/ajpheart.00086.2011

10.1016/B978-0-12-386525-0.00043-3

Marlett JA, Code CF. Effects of celiac and superior mesenteric ganglionectomy on interdigestive myoelectric complex in dogs. Am J Physiol. 1979;237:E432–E443.

Freedman MA, Hallenbeck GA, Code CF. The effect of vagotomy and of methantheline bromide on the diarrhea produced by celiac and superior mesenteric ganglionectomy. Surg Forum. 1953:481–486.

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Hypertension

Tập 61 Số 4

806-811

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