Abstract 538: Prolonged Functional Sympathetic Efferent Denervation Following Ablation of the Renal Nerves in SHR

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Renal denervation (RDN) has been shown to be an effective and safe treatment for human resistant hypertension and is considered one of the most promising advances in the field of hypertension. However, the mechanisms mediating the sustained decrease in arterial pressure in response to RDN in humans are unknown. This issue is particularly perplexing, given reports that the depressor effect of RDN in animal models is short lived. The current dogma in the literature is that overtime the efferent sympathetic nerves regrow and so the longevity of the depressor effect of RDN in humans cannot be ascribed to the absence of efferent renal sympathetic nerve activity. We hypothesize that the renal sympathetic nerves regenerate following RDN, and arrive at the target tissues, but the functional response is not fully restored and this contributes to the long-term depressor effect of RDN. Our aim was to examine mean arterial pressure (MAP) and vascular function in spontaneously hypertensive rats (SHR) following RDN. In 10 week old male SHR radiotelemetry probes were implanted to measure MAP. At 12 weeks of age, following 3 days basal MAP recording, sham (n=5) or bilateral RDN (n=5) surgery was performed. MAP was recorded until 24 weeks of age (12 weeks post-RDN). Renal lobar arteries were mounted on a myograph and membrane potential and tension responses to perivascular nerve stimulation assessed. Perivascular nerve stimulation with single pulses at increasing voltage evoked excitatory junction potentials (Ejps) of increasing amplitude in SHR-sham. Ejp amplitude was markedly reduced in arteries from SHR-RDN (P<0.01). Repetitive stimulation (1-8Hz, 5s) evoked slow depolarisation and contraction. At 5Hz 5s, slow depolarisation was 12±2 mV in SHR-shams and 7±2 mV in SHR-RDN (P<0.01), and contractions were smaller than SHR-sham (10 ± 3% vs 22 ± 2% HiK; P<0.01). In conclusion, smaller Ejps suggest that close contacting neuroeffector junctions are not reformed and blunted vasoconstrictor responses indicate neuro-vascular function has only partially returned 12 weeks post-RDN (Fig. 2). Our finding of continued ‘functional’ denervation is compatible with our data that RDN causes a sustained decrease in arterial pressure in SHR.

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