[For the first time, we demonstrated the fenestration in the endothelium of the distal portion of renal afferent arteriole (AA), which is unusual among high pressure vessels. The fenestrae are co-localized with renin producing granular epithelioid cells; this arrangement makes it likely that the relatively large renin molecules may use this path to enter into the plasma. We also demonstrated that the length and area of this fenestrated segment 1) correlates with the activity of the renin-angiotensin system (RAS), 2) may change by age, in response to some stimuli such as thirst and in some diseases, 3) allows filtration of fluid prior to the glomerular filtration, which can be as high as about 30% of GFR. This morphology and the high filtration volume in AA is one of the most striking observations of renal microcirculation, and question several basic renal physiological issues.]

[Diabetic nephropathy is the main cause of chronic kidney disease affecting about one-third of type 2 diabetic patients. The exact pathomechanism is not known, therefore the treatment and the prevention is still unsolved. However appropriate glycemic control and lowering blood pressure significantly slow the progression of kidney damage these treatment options are still not enough to stop renal injury. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest drugs in the treatment of diabetes. By inhibiting the glucose reabsorption in the proximal tubules SGLT2 inhibitors lower blood glucose level and facilitate glucosuria. This paper summarizes the effect of SGLT2 inhibitors currently approved in Europe paying particular attention to their possible renoprotective effects.]

[Dyslipidaemia is one of the known main risk factors of atherosclerosis by causing endothelial dysfunction that initiates and promotes vascular remodelling. Recent data from experimental and clinical studies suggest the existence of lipoprotein- neurohormonal interactions that may adversely affect vascular structure and function. Elevated lipid levels enhance the activation of the renin-angiotensin system, and, on the other hand, activation of the renin-angiotensin system leads to increased LDL cholesterol biosynthesis and oxidized-LDL uptake. These findings may explain the synergistic effect on cardiovascular risk observed in patients with coexisting hypertension and dyslipidaemia. The combined use of cholesterol-lowering drugs and inhibition of the tissue renin-angiotensin system may be more efficient in reducing cardiovascular risk.]

[Chronic stress is associated with increased levels of cortisol and catecholamines as well as with an enhanced activity of the sympathico-sensory nervous system. These neuroendocrine events influence both directly and indirectly the lipid and glucose metabolism as well as inflammatory immune reactions. Stress effects directly cause vascular damage and atherosclerosis via the renin-angiotensin system (RAS). Besides RAS, activities of monocytes/macrophages and the sympathico-sensory nervous system lead to local cardiovascular inflammation and cell hypertrophy. Transactivation between G-protein coupled adrenoceptors and tyrosine kinase receptors as well as the switching between β1- and β2- adrenergic receptors play an important role in the development of cardiac hypertrophy and heart failure. In all chronic neuroendocrine diseases that are associated with increased activity of the sympathetic nervous system, the development of cardiovascular damages needs to be considered.]

[Angiotensin II (Ang II) by activating angiotensin type 1 receptors (AT1R) is one of the most potent vasoconstrictors in the regulation of vasomotor tone and thus systemic blood pressure. In this study, we hypothesized that aging alters Ang II - induced vasomotor responses and expression of vascular mRNA and protein angiotensin type 1 receptor (AT1R). Thus, carotid arteries were isolated from newborn, young, middle age, old and senescent rats and their vasomotor responses were measured in a myograph (DMT-600) to repeated administrations of Ang II. Vascular relative AT1R mRNA level was determined by qRT-PCR and the AT1R protein density was measured by Western blot. Contractions of vessels to the first administration of Ang II increased from newborn to young and middle age rats then they decreased to senescent rats. In general, second administration of Ang II elicited reduced contractions, but they also first increased and then they decreased to old age. Similarly, the AT1R mRNA level and the AT1R protein density increased from newborn to young and middle age rats then they decreased to senescent rats. The pattern of these changes correlated with functional vasomotor data. We conclude that aging (newborn to senescence) has substantial effects on Ang II-induced vasomotor responses and AT1R signaling suggesting that it is - and thus regulation of systemic blood pressure is - determined primarily by genetic programs.]