{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:29:24Z","timestamp":1789475364070,"version":"build-2803163510"},"reference-count":95,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,2,20]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF).<\/jats:p>\n            <jats:p xml:lang=\"en\">We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Male ZSF1 obese rats were subjected to radiofrequency renal denervation (RF\u2010RDN) or sham procedure at either 8\u2009weeks or 20\u2009weeks of age and assessed for cardiovascular function, exercise capacity, and cardiorenal fibrosis. Renal norepinephrine and renal nerve tyrosine hydroxylase staining were performed to quantify denervation following RF\u2010RDN. In addition, renal injury, oxidative stress, inflammation, and profibrotic biomarkers were evaluated to determine pathways associated with RDN. RF\u2010RDN significantly reduced renal norepinephrine and tyrosine hydroxylase content in both study cohorts. RF\u2010RDN therapy performed at 8\u2009weeks of age attenuated cardiac dysfunction, reduced cardiorenal fibrosis, and improved endothelial\u2010dependent vascular reactivity. These improvements were associated with reductions in renal injury markers, expression of renal NLR family pyrin domain containing 3\/interleukin 1\u03b2, and expression of profibrotic mediators. RF\u2010RDN failed to exert beneficial effects when administered in the 20\u2010week\u2010old HFpEF cohort.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our data demonstrate that early RF\u2010RDN therapy protects against HFpEF disease progression in part due to the attenuation of renal fibrosis and inflammation. In contrast, the renoprotective and left ventricular functional improvements were lost when RF\u2010RDN was performed in later HFpEF progression. These results suggest that RDN may be a viable treatment option for HFpEF during the early stages of this systemic inflammatory disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.032646","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T11:28:31Z","timestamp":1707910111000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4584-4819","authenticated-orcid":false,"given":"Jake E.","family":"Doiron","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics Louisiana State University Health Sciences Center New Orleans LA 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