No abstract

Background-Hypertension is associated with impaired glucose metabolism and insulin resistance. Chronic activation of the sympathetic nervous system may contribute to either condition. We investigated the effect of catheter-based renal sympathetic denervation on glucose metabolism and blood pressure control in patients with resistant hypertension. Methods and Results-We enrolled 50 patients with therapy-resistant hypertension. Thirty-seven patients underwent bilateral catheter-based renal denervation, and 13 patients were assigned to a control group. Systolic and diastolic blood pressures, fasting glucose, insulin, C peptide, hemoglobin A 1c , calculated insulin sensitivity (homeostasis model assessment-insulin resistance), and glucose levels during oral glucose tolerance test were measured before and 1 and 3 months after treatment. Mean office blood pressure at baseline was 178/96Ϯ3/2 mm Hg. At 1 and 3 months, office blood pressure was reduced by Ϫ28/Ϫ10 mm Hg (PϽ0.001) and Ϫ32/Ϫ12 mm Hg (PϽ0.001), respectively, in the treatment group, without changes in concurrent antihypertensive treatment. Three months after renal denervation, fasting glucose was reduced from 118Ϯ3.4 to 108Ϯ3.8 mg/dL (Pϭ0.039). Insulin levels were decreased from 20.8Ϯ3.0 to 9.3Ϯ2.5 IU/mL (Pϭ0.006) and C-peptide levels from 5.3Ϯ0.6 to 3.0Ϯ0.9 ng/mL (Pϭ0.002). After 3 months, homeostasis model assessment-insulin resistance decreased from 6.0Ϯ0.9 to 2.4Ϯ0.8 (Pϭ0.001). Additionally, mean 2-hour glucose levels during oral glucose tolerance test were reduced significantly by 27 mg/dL (Pϭ0.012). There were no significant changes in blood pressure or metabolic markers in the control group. Conclusions-Renal denervation improves glucose metabolism and insulin sensitivity in addition to a significantly reducing blood pressure. However, this improvement appeared to be unrelated to changes in drug treatment. This novel procedure may therefore provide protection in patients with resistant hypertension and metabolic disorders at high cardiovascular risk. Clinical Trial Registration-URL: http://www.ClinicalTrials.gov. Unique identifiers: NCT00664638 and NCT00888433.

Despite carrying a minimal risk of adrenal vein rupture and at variance with the guidelines, AVS is not used systematically at major referral centers worldwide. These findings represent an argument for defining guidelines for this clinically important but technically demanding procedure.

Using immunohistological techniques and available polyclonal antibodies, we have identified several ATP-sensitive P2 receptor subtypes in specific structures of the normal rat kidney. Of the P2 receptor subtypes examined, P2X₁, P2X₂ and P2Y₁ receptors were found in the smooth muscle layer of intrarenal vessels. The P2Y₁ receptor was also found on glomerular mesangial cells, the brush border membrane of the proximal straight tubule and on peritubular fibroblasts. In the cortex, P2Y₄ receptors were found on the tubule epithelium of the proximal convoluted tubule, and P2Y₂ receptors on glomerular epithelial cells (podocytes). P2X₄ and P2X₆ receptors were present throughout the renal tubule epithelium from the proximal tubule to the collecting duct. P2X₅ receptors were expressed on medullary collecting duct cells and the apical membrane of the S3 segment of the proximal tubule. Possible functions of these receptor subtypes in normal rat kidney are discussed.

RDN reduced office BP and improved relevant aspects of ambulatory BP monitoring, commonly linked to high cardiovascular risk, in patients with true-treatment resistant hypertension, whereas it only affected office BP in pseudoresistant hypertension.