Cardiac Spinal Afferent Denervation Attenuates Renal Dysfunction in Rats With Cardiorenal Syndrome Type 2

Zhiqiu Xia; Neetha Nanoth Vellichirammal; Li Han; Lie Gao; Erika I Boesen; Alicia M Schiller; Peter R Pellegrino; Steven J Lisco; Chittibabu Guda; Irving H Zucker; Han-Jun Wang

doi:10.1016/j.jacbts.2022.02.008

Cardiac Spinal Afferent Denervation Attenuates Renal Dysfunction in Rats With Cardiorenal Syndrome Type 2

JACC Basic Transl Sci. 2022 Jun 22;7(6):582-596. doi: 10.1016/j.jacbts.2022.02.008. eCollection 2022 Jun.

Authors

Zhiqiu Xia¹, Neetha Nanoth Vellichirammal², Li Han^{1

3}, Lie Gao⁴, Erika I Boesen⁴, Alicia M Schiller¹, Peter R Pellegrino¹, Steven J Lisco¹, Chittibabu Guda^{2

5}, Irving H Zucker⁴, Han-Jun Wang^{1

4}

Affiliations

¹ Department of Anesthesiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
² Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, USA.
³ College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
⁴ Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
⁵ Bioinformatics and Systems Biology Core, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Abstract

Cardiorenal syndrome type 2 (CRS2) is defined as a chronic cardiovascular disease, usually chronic heart failure (CHF), resulting in chronic kidney disease. We hypothesized that the cardiac spinal afferent reflex (CSAR) plays a critical role in the development of CRS2. Our data suggest that cardiac afferent ablation by resiniferatoxin not only improves cardiac function but also benefits the kidneys and increases long-term survival in the myocardial infarction model of CHF. We also found that renal denervation has a similar reno-protective effect in CHF rats. We believe this novel work contributes to the development of a unique neuromodulation therapy to treat CHF patients.

Keywords: BUN, blood urea nitrogen; CHF, chronic heart failure; CRS2, cardiorenal syndrome type 2; CSAR, cardiac spinal afferent reflex; EF, ejection fraction; FS, fractional shortening; GFR, glomerular filtration rate; HR, heart rate; Kim-1, kidney injury molecule 1; MAP, mean arterial blood pressure; MI, myocardial infarction; Ngal, neutrophil gelatinase–associated lipocalin; RBF, renal blood flow; RTX, resiniferatoxin; RVR, renal vascular resistance; URDN, unilateral renal denervation; cardiorenal syndrome type 2; cardiovascular reflexes; chronic heart failure; inflammation; renal failure; sympathoexcitation.

Abstract

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