Abstract: BACKGROUND:Vascular resistance, and therefore blood pressure (BP), depends on vascular and rheological factors. Microrheological characteristics of red blood cells (RBCs) can affect blood viscosity (BV) and thus be included in the pathogenesis of increased blood pressure in arterial hypertension (AH). Signaling molecules such as gasotransmitters (NO, CO and H2S) regulate vascular tone and RBC microrheological characteristics and thus affect blood pressure and tissue perfusion. OBJECTIVE:It was evaluated the changes in the macro- and microrheological characteristics of blood and red blood cells (RBCs) under arterial hypertension in persons with and without COVID-19, as well as the protective effect of NO and H2S donors on the RBC microrheological properties. METHODS:Hemorheological profile parameters were recorded in group 1 individuals (n = 18, 9 women and 9 men) without a history of COVID-19; group 2 (n = 16; 11 females and 5 males), hypertensive patients who had COVID-19. As a control, there was a group of healthy individuals (group 3 n = 22). In experiments with red blood cells (RBCs) and their recovered ghosts (filled with an isotonic solution of known viscosity), deformability (RBCD) and aggregation (RBCA) were recorded after incubation of cells with sodium nitroprusside (SNP, 100μM) and sodium hydrosulfide (NaHS, 100μM). RESULTS:In patients with AH in both groups, the main parameters of the hemorheological profile were negatively changed, including a decrease in RBCD and an increase in BV, plasma viscosity (PV) and RBCA. SNP and NaHS significantly increased deformability and reduced their aggregation (p < 0.01). However, in healthy individuals, microrheological responses to GT donors (100μM) were more pronounced than in patients with AH, especially in the AH+COVID-19 group (p < 0.05). CONCLUSION:Both gasotransmitter donors (NO and H2S) have a positive effect on the RBC microrheological characteristics in healthy and sick individuals. However in hypertensive patients, especially those who had COVID-19, microrheological responses to GT donors were significantly lower. Therefore, on the model of red cell microrheological responses, as on a test object, it is possible to determine the decrease in the sensitivity of cells and tissues to the regulatory action of gasotransmitters.