Contribution of renal innervation to hypertension in rat autosomal dominant polycystic kidney disease

Vincent H. Gattone, Tibério M. Siqueira, Charles R. Powell, Chad M. Trambaugh, James E. Lingeman, Arieh L. Shalhav

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The kidney has both afferent (sensory) and efferent (sympathetic) nerves that can influence renal function. Renal innerva- tion has been shown to play a role in the pathogenesis of many forms of hypertension. Hypertension and flank pain are common clinical manifestations of autosomal dominant (AD) polycystic kidney disease (PKD). We hypothesize that renal innervation contributes to the hypertension and progression of cystic change in rodent PKD. In the present study, the contribution of renal innervation to hypertension and progression of renal histopathology and dysfunction was assessed in male Han:SPRD-Cy/+ rats with ADPKD. At 4 weeks of age, male offspring from crosses of heterozygotes (Cy/+) were randomized into either 1) bilateral surgical renal denervation, 2) surgical sham denervation control, or 3) nonoperated control groups. A midline laparotomy was performed to allow the renal denervation (i.e., physical stripping of the nerves and painting the artery with phenol/alcohol). Blood pressure (tail cuff method), renal function (BUN) and histology were assessed at 8 weeks of age. Bilateral renal denervation reduced the cystic kidney size, cyst volume density, systolic blood pressure, and improved renal function (BUN) as compared with nonoperated controls. Oper-ated control cystic rats had kidney weights, cyst volume densities, systolic blood pressures, and plasma BUN levels that were intermediate between those in the denervated animals and the nonoperated controls. The denervated group had a reduced systolic blood pressure compared with the operated control animals, indicating that the renal innervations was a major contributor to the hypertension in this model of ADPKD. Renal denervation was efficacious in reducing some pathology, including hypertension, renal enlargement, and cystic pathology. However, sham operation also affected the cystic disease but to a lesser extent. We hypothesize that the amelioration of hypertension in Cy/+ rats was due to the effects of renal denervation on the renin angiotensin system.

Original languageEnglish (US)
Pages (from-to)952-957
Number of pages6
JournalExperimental Biology and Medicine
Volume233
Issue number8
DOIs
StatePublished - Aug 1 2008

Keywords

  • Cy/+ rat
  • Denervation
  • Hypertension
  • Polycystic kidney disease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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