Abstract 256: Renal Denervation Preconditions the Myocardium by Promoting Nitric Oxide Signaling and Attenuating Oxidative Stress in Spontaneously Hypertensive Rats

Abstract

Background: Recent clinical studies suggest that renal denervation (RDN) not only decreases blood pressure (BP) and sympathetic nerve activity, but may also exert additional systemic cardioprotective actions. We investigated whether RDN preconditions the heart against subsequent myocardial ischemia/reperfusion (MI/R) injury in spontaneously hypertensive rats (SHR). Materials and Methods: SHR (20w old) received either bilateral radiofrequency (RF) RDN or sham RDN (Biosense Webster Stockert 70 RF generator). After 4w of BP recording, Plasma and left ventricle (LV) tissue were collected for measurement of nitric oxide (NO) metabolites, nitrite (NO2-, ion chromatography) and S-Nitrosothiol (RSNO). RT PCR was used to examine transcriptional changes. Colorimetric assays were used to quantify malondialdehyde (MDA) and carbonyl content. In additional studies, 4w after RDN (n = 8) or Sham (n = 9) treatment, SHR were subjected to 30m of left coronary artery ischemia followed by 24h reperfusion and myocardial infarct/area-at-risk (AAR) was determined. Results: 4w after treatment, mean BP was significantly decreased in RDN compared to Sham SHR (157±2 vs 142±2 mmHg, p < 0.05). Plasma NO2- levels were elevated 4w following RDN (p < 0.01). Cardiac NO2- levels increased from 2.6 to 3.2 nmol/mg (p < 0.05) and RSNO levels increased from 0.5 to 1.1 nmol/mg (p < 0.05) following RDN. Moreover, myocardial oxidative stress was markedly attenuated as measured by carbonyl content (p < 0.05) and MDA levels (p < 0.01). Greater transcription of antioxidants, SOD1 (p < 0.05) and GPX-1 (p < 0.05) were also observed in the RDN treated group. SHR receiving RDN therapy exhibited a trend in infarct size reduction (42% per AAR reduction, p = 0.09) compared to sham following MI/R. We observed 2-fold greater survival in the RDN treated group (88%, 7 of 8) compared to sham (44%, 4 of 9) following MI/R. Conclusions: RDN produced a sustained elevation in NO bioavailability and signaling in the heart and blood. Additionally, RDN attenuated myocardial oxidative stress and augmented the antioxidant defense system in SHR. Although further studies are warranted, preliminary results indicate that these mechanisms may promote myocardial preconditioning and improve survival in the setting of MI/R injury.