ABSTRACT
AIM: To elicit the role of endothelial dysfunction in development of cardiorenal syndrome in patients with diabetes mellitus type 1 (DM1) with diabetic nephropathy (DN) and to evaluate the efficacy of endotheliotropic drugs: nebivolol (a selective beta-blocker) and enalapril (ACE inhibitor). MATERIAL AND METHODS: The trial enrolled 60 patients with DM1: 15 patients with normoalbuminuria (NAU), 15 patients with microalbuminuria (MAU), 15 patients with proteinuria (PU) and 15 with chronic renal failure (CRF). The control group consisted of 15 healthy volunteers matched by sex and age. All the patients were examined for endothelium-dependent dilation of the brachial artery (by duplex scanning in the test with reactive hyperemia), serum markers of endothelial dysfunction (endothelin-1--ET-1), Willebrand factor (WF), inflammation markers (C-reactive protein-CRP), incidence rate of ischemic heart disease (IHD). 24-h arterial pressure monitoring and echocardiography were also made. For 12 weeks the patients were given nebivolol monotherapy in a dose 5 mg/day or enalapril monotherapy in a dose 10 mg/day. The effects of these drugs on urinary excretion of albumin and protein, arterial pressure, circadial rhythm of arterial pressure and endothelial dysfunction were studied. RESULTS: In DM1 patients DN advances with an increase in development of IHD: in MAU--by 13%, PU--by 33%, CRF--53%. Concentric hypertrophy and left ventricular remodeling were registered in 33, 40 and 60% of cases, respectively. A circadian rhythm disturbance correlated with DN severity. DN progression was associated with increasing endothelial dysfunction. It is shown that nebivolol and enalapril correct endothelial dysfunction, have comparable antiproteinuric and antihypertensive actions at different stages of nephropathy. CONCLUSION: A close correlation was found between DN progression and development of cardiovascular pathology in DM1 patients. This serves the basis of cardiorenal syndrome. These two pathologies are associated with vascular endothelial dysfunction which leads to disorders in vascular tonicity regulation.
