[Effect of chronic kidney disease on the formation of diastolic heart dysfunction in heart failure patients with preserved ejection fraction].

Chronic kidney disease is observed in most patients with CHF with preserved ejection fraction (HFpEF) and presents a major risk factor facilitating development and progression of LV diastolic dysfunction. The review focused on the effect of chronic kidney disease on intracellular signaling pathways affecting stiffness and diastolic relaxation of cardiomyocytes in response to inflammation and endothelial dysfunction of coronary capillaries, excessive sympathetic activation, and dysregulation of natriuretic peptides, which directly participate in the development of CHF. Elucidation of these mechanisms allows to identify new cell targets for new approaches to drug therapy for patients with HFpEF.

[INTERACTION OF BETA-BLOCKER PROPRANOLOL WITH RENIN-ANGIOTENSIN SYSTEM INHIBITORS IN RAT KIDNEY].

Propranolol injection (0.5 mg/kg, s.c.) in anesthetized rats increases diuresis 1.60 times (p < 0.05) with simultaneous 1.54- and 1.62-fold increase (p < 0.05) in sodium and potassium excretion, respectively. Preliminary inhibition of renin-angiotensin system (RAS) activity using ACE inhibitor enalapril (1 mg/kg, orally, 7 days) increases the sensitivity of rat kidney to drug, increasing its diuretic effect 2.33 times, natriuresis 2.49 times, and urine potassium excretion 1.80 times (p < 0.05). After the preliminary insertion of AT1 angiotensin receptor antagonist losartan (1 mg/kg, orally, 7 days), propranolol causes 1.8-fold increase in diuresis, 2.48-fold decrease in urine sodium, and 1.71-fold decrease in kaliuresis (p < 0.05). Preliminary administration of direct renin inhibitor aliskiren (4 mg/kg, orally, 7 days) is accompanied by 2.30-fold increase in the diuretic effect of propranolol, 2.56-fold increase in natriuresis, and 2.27-fold increase in urine potassium excretion (p < 0.05). It is concluded that the renal tissue RAS is involved in the mechanism of propranolol action in the kidney, acting as modulator preventing excessive loss of water and electrolytes with urine.

[Interaction of renin-angiotensin system inhibitors with dopamine in rat kidney].

Dopamine (1 mg/kg, s.c.) causes 2.2-fold increase in diuresis (p < 0.05) in anesthetized rats, which is accompanied by an increase in the urinary excretion of sodium and potassium by a factor of 2.2 and 2.8, respectively (p < 0.05). Preliminary administration of the ACE inhibitor enalapril (1 mg/kg, p.o., for 7 days) enhances the renal dopamine response with 3.5-fold increase in its diuretic effect and increases natriuresis 3.2 times and urine potassium excretion 5 times (p < 0.05). After preliminary introduction of the AT1-angiotensin receptor antagonist losartan (1 mg/kg, p.o., for 7 days) dopamine causes 3.3-fold increase in diuresis, 3.1-fold increase in natriuresis, and 3-fold increase in kaliuresis (p < 0.05). Preliminary administration of the direct renin inhibitor aliskiren (4 mg/kg, p.o., for 7 days) is accompanied by 6-fold increase in the diuretic effect of dopamine and increases natriuresis 7.2 times and urine potassium excretion 7 times (p < 0.05). It is concluded that renin-angiotensin system (RAS) of renal tissues is involved in the mechanism of dopamine action in the kidney, acting as a modulator that prevents excessive loss of water and electrolytes with urine.

[Effect of the third generation beta-blockers on ion-regulating renal function in rats with heart failure model].

Beta-adrenoceptor blockers nebivolol and carvedilol do not affect diuresis and renal sodium excretion in intact rats, but significantly increase urinary excretion of sodium in animals with a model of heart failure caused by excessive physical exercise and injection of phenylephrine. Nebivolol, in contrast to carvedilol, causes additional increase the urinary potassium loss, which is retained in animals with experimental heart failure. It is concluded that both drugs increase renal sodium excretion in rats with heart failure model by preventing the excessive sodium delay in the body.