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Regular Manuscript

Contribution of Renal Innervation to Hypertension in Rat Autosomal Dominant Polycystic Kidney Disease

¹ Indiana Univ Sch of Med
² Getúlio Vargas Hospital, Urology
³ The University of Illinois at Chicago
⁴ Indiana University School of Medicine
⁵ Methodist Hospital Institute for Kidney Stone Disease
⁶ The University of Chicago

^* To whom correspondence should be addressed. E-mail: vgattone{at}iupui.edu.

	Abstract

Background/Aims: The kidney has both afferent (sensory) and efferent (sympathetic) nerves that can influence renal function. Renal innervation 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) polcystic 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. Methods: 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) non-operated 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. Results: Bilateral renal denervation reduced the cystic kidney size, cyst volume density, systolic blood pressure and improved renal function (BUN) as compared to non-operated controls. Operated 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 non-operated controls. The denervated group had a reduced systolic blood pressure compared to the operated control animals indicating that the renal innervations was a major contributor to the hypertension in this model of ADPKD. Conclusions: 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 effects of renal denervation on renin angiotensin system.

Key Words: polycystic kidney disease, rat, hypertension, kidney, denervation