Effect Of Catheter-based Renal Sympathetic Denervation On Norepinephrine Level In Hypertensive Canine Model And The Mechanism Involved

Objective:To investigate the effect of catheter-based radiofrequency renal sympathetic denervation (RDN) on serum and kidney norepinephrine (NE) level in hypertensive canine model. Secondarily, we investigated the possible mechanism of how renal sympathetic nerve activity affecting NE by observing the expression of renal NE metabolites-related substances Tyrosine Hydroxylase (TH), Catechol-O-Methyl Transferase (COMT), Renalase, and Norepinephrine Transporter (NET) following RDN as the possible mechanism involved.Methods:Twenty eight Beagles were divided into hypertension model group (n=22) and control group (n=6). Hypertension model was established by high fat diet feeding. Once the model was established, animals were divided into RDN group (n=10) which underwent catheter-based radiofrequency renal sympathetic denervation and sham group (n=10) which underwent only renal angiography. Using a non-invasive tail sphygmomanometer, blood pressure was measured at several time points as follow:baseline, pre-procedure, and post-procedure (1,2,4, and6months). Six months following the procedure, all the animals were sacrificed and the kidneys were quickly extirpated.6months after renal denervation, animals in each group were sacrificed and blood, kidneys were collected for examination. TH, COMT, Renalase, and NET protein expression were examined with Western Blot and Immunohistochemistry (IHC). TH and Renalase mRNA expression were determined with Real Time PCR. Serum and renal NE level were examined with High Performance Liquid Chromatography (HPLC).Results:(1) Compared to the control group, body weight and blood pressure in the model group increased significantly (P<0.05). In RDN group, post-operative systolic blood pressure (SBP), diastolic blood pressure (DBP), as well as mean arterial blood pressure (MAP) at1,2,4, and6months decreased significantly when compared to pre-operative data and sham group (all P<0.05).(2) Six months following RDN, both serum and renal NE level was found significantly lower than sham group (P<0.05). Serum and renal NE level was higher than of those in control group (P<0.05). Renal TH mRNA and protein expression in RDN group were remarkably lower (p<0.05) while Renalase mRNA and protein expression were higher than sham group (p<0.05). Renalase expression in sham group was markedly lower than control group (p<0.05). COMT protein expression in both control and RDN group was higher than sham group. However, the difference was not statistically significant (P>0.05). No significant difference of NET protein expression between groups (P>0.05). However, NET expression was found higher in RDN group when compared to sham group.(3) Serum and renal NE levels positively correlated with SBP; TH expression and NE levels were positively correlated; Renalase expression and renal NE levels were negatively correlated.Conclusion:In the hypertensive canine model, the elevation of blood pressure was associated with the increase in serum and renal NE level. RDN effectively reduced blood pressure and decreased serum as well as renal NE possibly through inhibiting renal TH and upregulating Renalase expression.