Whereas classical beta-blockers do not affect cell growth, only nebivolol inhibits haCSMC or haEC proliferation and induces a moderate rate of apoptosis. Furthermore, in HaCEs NO formation increases and endothelin-1 secretion decreases suggesting that nebivolol may represent a beta-blocker with great promises in CAD therapy.

Aims To examine the cutaneous microcirculation on the dorsum of the foot before, during and after haemodialysis in diabetic and non-diabetic patients. MethodsFourteen age-matched patients (seven diabetic, seven non-diabetic) without active foot ulceration were studied. Cutaneous microcirculation was assessed using a micro-lightguide spectrophotometer to measure venous oxygen saturation and relative blood flow determined at two tissue depths: 2 and 6 mm. Cumulative relative changes of each parameter during haemodialysis were calculated as area under the curve. Differences between and within the groups were calculated by Mann-Whitney U -test and ANOVA following post hoc testing, respectively.Results At baseline, relative blood flow at 6 mm tissue depth was significantly greater in diabetic patients ( P = 0.048). Thirty minutes after the end of dialysis, relative blood flow at 2 and 6 mm tissue depth was significantly higher in nondiabetic patients ( P = 0.048 and P = 0.001). Mean cumulative relative changes in venous oxygen saturation and relative blood flow at 2 mm as well as 6 mm tissue depth were positive for non-diabetic subjects and negative for diabetic patients. ConclusionsHaemodialysis is associated with changes in cutaneous microcirculation, which differ between people with and without diabetes. In those without diabetes, we found an increase in blood flow during haemodialysis, whereas blood flow was reduced in diabetic patients. This may be the result of abnormal vasomotor regulation due to distal neuropathy. Diabet. Med. 26, 89-92 (2009)

Endothelin-1 (ET-1) plays an important role in atherogenesis. The aim of the study reported here was to investigate the effects of the third generation beta-blockers nebivolol and carvedilol on ET-1 liberation, preproendothelin-1 production and on proliferation of human coronary cells. Human coronary endothelial (HEC) and smooth muscle cells (HCSMC) were grown with carvedilol or nebivolol (10(-7)-10(-5) mol/l). Incubation for 1, 2 or 7 days resulted in an 80% concentration- and time-dependent reduction in HCSMC proliferation. beta-blockers such as propranolol or metoprolol did not influence cell proliferation. Nebivolol (10(-7) mol/l) inhibited accelerated HCSMC proliferation in the presence of growth factors such as transforming growth factor-beta1 or platelet-derived growth factor BB. During incubation with nebivolol or carvedilol ET-1 secretion decreased. For nebivolol this is a result of a reduction in preproendothelin-1 mRNA levels. beta-blockers of the third generation that reduce the cell proliferation and ET-1 secretion may represent strategies with great promise for antiproliferative therapy of coronary heart disease.

Objective and Background: Inflammation plays a critical role in all stages of atherogenesis. Proliferating vascular smooth muscle cells (SMC) and endothelial cells (EC) enhancing the inflammatory response, both contribute to the progression of atherosclerosis. Anti-proliferative, anti-inflammatory and anti-oxidative therapy seems to be a promising therapeutic strategy. The aim of this study was to assess the anti-proliferative and anti-inflammatory effect of the β-blocker nebivolol in comparison to metoprolol in vitro and to find out whether nebivolol inhibits neointima formation in vivo. Methods and Results: Real-time-RT-PCR revealed a decrease in VCAM-1, ICAM-1, PDGF-B, E-selectin and P-selectin mRNA expression in human coronary artery EC and SMC incubated with nebivolol for 72 hours while metoprolol did not have this effect. Nebivolol reduced MCP-1 and PDGF-BB protein in the culture supernatant of SMC and EC, respectively. Sprague-Dawley rats were treated with nebivolol for 0 or 35 days before and 28 days after carotid balloon injury. Immunohistological analyses showed that pre-treatment with nebivolol was associated with a decreased number of SMC layers and macrophages and an increased lumen area at the site of the arterial injury. The intima area was reduced by 43% after pre-treatment. Conclusion: We found that nebivolol reduced the expression of proinflammatory genes in endothelial cells and vascular smooth muscle cells in vitro whereas metoprolol did not. In vivo, nebivolol inhibited neointima formation by reducing SMC proliferation and macrophage accumulation.

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