The cholinergic anti-inflammatory pathway in resistant hypertension treated with renal denervation.

BACKGROUND: Renal denervation (RDN) reduces sympathetic tone and may alter the sympathetic-parasympathetic balance. The autonomic nervous system is partly a regulator of innate immunity via the cholinergic anti-inflammatory pathway (CAP) which inhibits inflammation via the vagus nerve. Placental Growth Factor (PlGF) influences a neuro-immunological pathway in the spleen which may contribute to hypertension. The aim of this study was to investigate if modulation of renal sympathetic nerve activity affects CAP in terms of cytokine release as well as levels of PlGF. METHODS: Ten patients treated with RDN (Medtronic Inc), were analyzed for TNF, IL-1b and IL-10 and Lipopolysaccharide (LPS)-stimulated cytokine release before RDN, 1 day after and at 3- and 6-months follow-up. Four patients who underwent elective coronary angiography served as disease controls (DC). RESULTS: Baseline TNF was significantly lower 1 day after RDN (p = 0.03). LPS-stimulated (0, 10 and 100 ng/mL) TNF and IL-1b were significantly lower 1 day after RDN (TNF p = 0.0009, p = 0.0009 and p = 0.001, IL-1b; p = 0.0001, p = 0.002 and p = 0.005). IL-10 was significantly higher one day after RDN (p = ns, p = 0.02 and p = 0.01). These differences however declined during follow up. A more marked TNF reduction was achieved with a cholinergic analogue, GTS-21, in LPS-stimulated whole blood as compared with samples without GTS-21. Cytokine levels in controls did not differ before and 1 day after coronary angiography. PlGF was significantly higher in RDN patients and DC compared with healthy controls but did not change during follow-up. CONCLUSION: RDN has an immediate effect on TNF in vivo and cytokine release ex vivo but seems to wane over time suggesting that current RDN techniques may not have long-lasting immunomodulatory effect. Repeated and extended stimulation of CAP in resistant hypertension by targeting neural circuits may be a potential therapeutic strategy for treatment of both hypertension and inflammation.

Renal sympathetic denervation in Sweden: a report from the Swedish registry for renal denervation.

BACKGROUND: Renal denervation (RDN) is a catheter-based intervention to treat patients with resistant hypertension. The biological effects of RDN are not fully understood, and randomized controlled trials have generated conflicting evidence. This report presents data from the Swedish Registry for Renal Denervation, an investigator-driven nationwide registry. PURPOSE: To assess the safety and efficacy of RDN on patients with resistant hypertension in a real-world clinical setting. METHODS: This nationwide database contains patient characteristics, procedural details, and follow-up data on all RDN procedures performed in Sweden. Consecutive procedures between 2011 and 2015 were included. RESULTS: The data analysis consists of 252 patients (mean age 61 ±â€Š10 years, 38% women; mean 4.5 ±â€Š1.5 antihypertensive drugs). Office SBP and DBP and 24-h ambulatory blood pressure (BP) decreased 6 months after RDN (176 ±â€Š23/97 ±â€Š17 to 161 ±â€Š26/91 ±â€Š16 mmHg, both P < 0.001; and 155 ±â€Š17/89 ±â€Š14 to 147 ±â€Š18/82 ±â€Š12 mmHg, both P < 0.001). Significant office and ambulatory BP reductions persisted throughout the observation period of 36 months. Major procedure-related vascular complications occurred in four patients. Renal function and number of antihypertensive drugs were unchanged during follow-up. CONCLUSION: In this complete national cohort, RDN was associated with a sustained reduction in office and ambulatory BP in patients with resistant hypertension. The procedure proved to be feasible and associated with a low-complication rate, including long-term adverse events.

Skin microvascular dilatation response to acetylcholine and sodium nitroprusside in peripheral arterial disease.

UNLABELLED: The relative magnitude of endothelial versus non-endothelial vasodilatation in the skin of limbs of patients with peripheral arterial occlusive disease (PAOD) is not known. We therefore investigated the effects of iontophoretically administered sodium nitroprusside (SNP) and acetylcholine (Ach) on the skin microvascular blood flow measured by laser-Doppler fluxmetry. METHODS: Blood flow changes in the skin was measured on the dorsal side of the foot in three different groups: (i). 11 patients (mean age 73 years) with PAOD, with a mean ankle-brachial index of 0.46, (ii). eight age-matched elderly healthy volunteers (mean age 73 years) and (iii). young healthy group (n=15; mean age 34 years). For drug administration with iontophoretic technique we used a Periont Micropharmacology System. RESULTS: In patients with PAOD, Ach produced a vasodilatation, which was directly correlated to the strength of iontophoretic stimulation. The difference between the patients and the elderly healthy group was significant after the highest stimulation (160 s, P<0.05). The same pattern was found during stimulation with SNP. In comparison with the young healthy group there was a statistically significant difference (P<0.001) with a slower and less pronounced response in patients with PAOD. CONCLUSION: In patients with PAOD it is possible to achieve local vasodilatation from a baseline level by delivering Ach or SNP through the skin. The two vasodilators, acting by different mechanisms, produced the same vasodilatation response, suggesting that the impaired vasodilatation capacity in patients with peripheral arterial disease may not emanate primarily from local endothelial dysfunction in the skin microcirculation.