Radiofrequency Renal Denervation Improves Vascular Reactivity in a Rodent Model of Heart Failure
Authors: Trivedi Rishi K , Li Zhen , Polhemus David J , Koiwaya Hiroshi , Goodchild Traci T , Lefer David J 
Published: November 2023

Background

We have previously reported that radiofrequency (RF) renal denervation (RDN) exerts cardioprotective effects in the setting of myocardial ischemia‐reperfusion (MI‐R) injury. The protective actions of RF‐RDN in MI‐R injury are related in part to attenuated oxidative stress and increased nitric oxide (NO) bioavailability. More recently we have demonstrated that RF‐RDN protects the failing heart independent of reductions in blood pressure. The mechanisms by which RF‐RDN affords these benefits have not been fully described, including the effects on vascular function.

Methods

Male Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at 20 weeks of age were subjected to 45 minutes of transient LAD coronary artery ligation followed by reperfusion for 12 weeks. Four weeks following reperfusion animals were subjected to either bilateral RF‐RDN or a sham procedure (SHAM) with n=12 in all groups. At 12 weeks after reperfusion, thoracic aorta was harvested and vascular reactivity was evaluated. Vasoactivity was assessed for the endothelium‐dependent vasodilators acetylcholine (ACh, 0.1nM–10mM) and the calcium ionophore A23187 (A23187, 10nM‐1mM). In addition, vascular reactivity to the endothelium‐independent vasodilator sodium nitroprusside (SNP, 0.1nM–10 mM) was investigated. The effects of RF‐RDN therapy on cardiac structure and function were also determined via biweekly 2‐D serial echocardiography.

Results

RF‐RDN significantly improved cardiovascular function as reflected in improved left ventricle (LV) ejection fraction at 12 weeks following reperfusion in both SHRs (46.8 ± 2.4% vs. 30.4 ± 2.5%, p<0.01) and WKYs (50.4 ± 3.0% vs 35.4 ± 2.7%; p<0.05). RF‐RDN treatment significantly improved endothelium mediated vasorelaxation in both hypertensive and normotensive animals as reflected in ACh EC50 (SHR: 98.8 ± 19.2 nM vs. 349.6 ± 25.0 nM, p<0.0001; WKY: 10.03 ± 1.32 nM vs. 44.97 ± 12.03 nM, p<0.01). Similar improvements were seen in smooth muscle mediated vasorelaxation due to SNP (SHR: 29.4 ± 4.2 nM vs. 145.3 ± 14.2 nM, p<0.0001; WKY: 11.68 ± 1.28 nM vs 39.68 ± 7.47 nM, p<0.01). RF‐RDN also improved vasorelaxation to the direct endothelium‐dependent vasodilator, A23187, in hypertensive animals (SHR: 10.8 ± 1.3 nM vs. 23.2 ± 2.7 nM, p<0.001) but not normotensive animals. We did not observe any significant reductions in blood pressure in either the SHR or WKY rats following RF‐RDN at anytime during the experimental protocol.

Conclusion

RF‐RDN significantly improved LV function in the setting of heart failure independent of blood pressure reductions. Therapy improved vascular function suggesting that the cardiovascular benefits afforded by RF‐RDN may be partially due to improved vascular function. The improved vascular reactivity and cardiac function observed following RF‐RDN may be a result of reduced oxidative stress and increased NO bioavailability. Experiments are currently underway to evaluate this possibility. Our results reveal a novel mechanism related to the beneficial effects of RF‐RDN in heart failure.