Erythrocyte membranes beta-adrenoreactivity changes after renal denervation in patients with resistant hypertension, relationship with antihypertensive and cardioprotective intervention efficacy

Aim To study the functional condition of sympathoadrenal system as evaluated by beta-adrenoreactivity of erythrocyte membranes (beta-ARM) during two years following renal denervation (RD) in patients with resistant arterial hypertension (RAH) and to determine the relationship of this index with long-term antihypertensive and cardioprotective effectivity of this invasive treatment.Material and methods The study included 48 patients (mean age, 57.2±8.7 years, 18 men) with RAH on a stable antihypertensive therapy. Averaged daily systolic and diastolic blood pressure (SBP and DBP) and levels of beta-ARM were determined at baseline and in 7 days and 2 years following RD. Measurement of beta-ARM was based on beta-adrenoblocker inhibition of erythrocyte hemolysis induced by exposure to hypo-osmotic environment. The beta-adrenoblocker binds to erythrocyte membrane beta-adrenoceptors to prevent the erythrocyte destruction. Increased values of beta-ARM reflect a decrease in the number of functionally active erythrocyte membrane beta-adrenoceptors associated with long-term sympathetic hyperactivity.Results For two years of follow-up, values of average daily BP decreased from 160.4±16.0 / 88.1±14.6 to 145.3±19.3 / 79.4±13.6 mm Hg. At 7 days, the number of beta-ARM had decreased in the group of RD responders (р=0.028) who at two years had decreased their BP by 10 mm Hg or more, while in the group of non-responders, the number of beta-ARM remained unchanged. At one week, beta-ARM values correlated with changes in SBP and DBP (r= –0.54; р<0.05) and with left ventricular myocardial mass (LVMM) (r= –0.36; р<0.05) at two years of follow-up whereas beta-ARM delta at one week was interrelated with the renin concentration in the long-term (r= –0.44; р<0.05). At two years, the content of beta-ARM was increased in both groups.Conclusion The decrease in beta-ARM content at 7 days after RD shows the procedure efficacy and allows an expectation of clinically significant decreases in BP and LVMM in the long-term after the surgical treatment. At two years after the intervention, the content of beta-ARM increased, and the BP decrease was apparently due to some other mechanisms.

Systematic Review and Meta-Analysis Protocol: Beta adrenoreceptor drugs and risk of Parkinsons disease

Parkinsons disease (PD) is a progressive nervous system disorder characterised by the loss of dopaminergic neurons leading to motor and non-motor symptoms. Accumulation of α-synuclein protein (SNCA) in the form of Lewy bodies has been observed in dopaminergic neurons of PD patients. Potential relationships between β-adrenergic drugs (agonists and antagonist) and SNCA synthesis in PD have been recently suggested. This study aims to systematically review the evidence from various epidemiological studies that analysed the association between beta-adrenoceptors (agonists and antagonists) and the risk of PD. Biomedical databases such as PubMed and Embase will be searched to identify the individual studies that reported the relationship between beta-adrenoceptors and the risk of PD. JBI critical appraisal tool scale will be used to assess the quality of included studies. The primary outcome will be to compute the pooled risk of PD among beta-agonist and antagonist users. Furthermore, we will consider the pooled risk of PD based on study design, types of beta-agonist or antagonist exposure under secondary outcomes. RevMan 5, STATA 16, and ProMeta 3.0 will be used to conduct the statistical analysis.

Pharmacological and Genetic Evidence of Dopamine Receptor 3-Mediated Vasoconstriction in Isolated Mouse Aorta

Dopamine receptors (DRs) are generally considered as mediators of vasomotor functions. However, when used in pharmacological studies, dopamine and/or DR agonists may not discriminate among different DR subtypes and may even stimulate alpha1 and beta-adrenoceptors. Here, we tested the hypothesis that D2R and/or D3R may specifically induce vasoconstriction in isolated mouse aorta. Aorta, isolated from wild-type (WT) and D3R−/− mice, was mounted in a wire myograph and challenged with cumulative concentrations of phenylephrine (PE), acetylcholine (ACh), and the D3R agonist 7-hydrxy-N,N-dipropyl-2-aminotetralin (7-OH-DPAT), with or without the D2R antagonist L741,626 and the D3R antagonist SB-277011-A. The vasoconstriction to PE and the vasodilatation to ACh were not different in WT and D3R−/−; in contrast, the contractile responses to 7-OH-DPAT were significantly weaker in D3R−/−, though not abolished. L741,626 did not change the contractile response induced by 7-OH-DPAT in WT or in D3R−/−, whereas SB-277011-A significantly reduced it in WT but did not in D3R−/−. D3R mRNA (assessed by qPCR) was about 5-fold more abundant than D2R mRNA in aorta from WT and undetectable in aorta from D3R−/−. Following transduction with lentivirus (72-h incubation) delivering synthetic microRNAs to specifically inactivate D2R (LV-miR-D2) or D3R (LV-miR-D3), the contractile response to 7-OH-DPAT was unaffected by LV-miR-D2, while it was significantly reduced by LV-miR-D3. These data indicate that, at least in mouse aorta, D3R stimulation induces vasoconstriction, while D2R stimulation does not. This is consistent with the higher expression level of D3R. The residual vasoconstriction elicited by high concentration D3R agonist in D3R−/− and/or in the presence of D3R antagonist is likely to be unrelated to DRs.