Radiofrequency Renal Denervation Protects the Ischemic Heart via Inhibition of GRK2 and Increased Nitric Oxide Signaling
Rationale: Catheter-based renal denervation (RDN) is currently under development for the treatment of resistant hypertension and is thought to reduce blood pressure via interruption of sympathetic pathways that modulate cardiovascular function. The sympathetic nervous system also plays a critical role in the pathogenesis of acute myocardial infarction and heart failure.
Objective: We examined whether treatment with radiofrequency (RF)-RDN would protect the heart against subsequent myocardial ischemia/reperfusion (MI/R) injury via direct effects on the myocardium.
Methods and Results: Spontaneously hypertensive rats (SHR) received either bilateral RF-RDN or sham-RDN. At 4 weeks following RF-RDN (n = 14) or Sham-RDN (n = 14) treatment, SHR were subjected to 30 min. of transient coronary artery occlusion and 24 hr - 7d reperfusion. 4 weeks following RF-RDN, myocardial oxidative stress was markedly attenuated and transcription and translation of antioxidants, SOD1 and GPX-1, were significantly upregulated compared to Sham-RDN SHR. RF-RDN also inhibited myocardial GRK2 pathological signaling and enhanced myocardial eNOS function and nitric oxide signaling. RF-RDN therapy resulted in a significant reduction in myocardial infarct size per area-at-risk (AAR) compared to Sham-RDN (26.8 vs. 43.9%, p < 0.01) at 24 hours post-reperfusion and significantly improved left ventricular function at 7 days following MI/R.
Conclusions: RF-RDN reduced oxidative stress, inhibited GRK2 signaling, increased NO bioavailability, and ameliorated myocardial reperfusion injury in the setting of severe hypertension. These findings provide new insights into the remote cardioprotective effects of RF-RDN acting directly on cardiac myocytes to attenuate cell death and protect against ischemic injury.
- Renal Denervation
- nervous system, sympathetic
- nitric oxide
- G protein-coupled receptor kinases
- oxidative stress
- Received December 31, 2015.
- Revision received June 7, 2016.
- Accepted June 13, 2016.
Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDervis License (http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.