Pharmacological analysis of the effectiveness of calcium blockers and NO synthesis modulators to correct arterial pressure during hemorrhagic shock

T. Sanikidze, M. Mantskava, E.Zvetkova, N. Antonova

Abstract: Hemorrhagic shock (HS) is a type of hypovolemic shock when abundant blood loss (hemorrhage) causes a decrease in circulating blood volume - leading to a weakness in the heart muscle strength, lowering in arterial blood pressure and venous outflow, as well as a shock development. Thus, the key link of the hemorrhagic shock is the disbalance between the mass of circulating blood and the volume of blood vessels. The aim of the study was to evaluate the pharmacological effects of calcium blockers and NO-synthase modulators, on the correction of blood arterial pressure (BAP) during hemorrhagic shock. HS was induced on mature Wistar white rats by intensive blood loss from the carotid artery (BAP decreased to 55±5 mm Hg). The dynamic of BAP was monitored using a mercury manometer with a cannula fixed in the animals sleepy artery. For the pharmacological analysis of BAPs alterations, the calcium antagonist (Isoptin), NO-synthase inhibitor (LNAME), and antioxidant (Plaferon LB) were used (5 minutes before the HS induction). Free nitric oxide (NO), endothelin-1 content in blood, and Ca2+ ions content in the pulmonary artery (PA) were measured. Statistical analysis of the results obtained was performed using the standard program. We made a reliable estimate of the differences using the Students t criterion. 15 minutes after the development of HS, the BAP began monotonically decreased and on the 15th minute reached 40 mmHg. Pre-administration of Isoptin, L-NAME, and Plaferon LB induced an increase of the BAP for 15th minutes of the development of the HS - to 80-85 mm Hg. On the 15th minutes of HS, the content of NO and endothelin-1 in the blood sharply increased (by 66% and 18%), Ca2+-ions content in the PA increased by 100%.
Against the pre-administration of LNAME in rats on the 15th minute of HS, the content of NO and endothelin-1 in the blood decreased by 56% and 23%, respectively,    Ca2+-ions content in PA decreased by 49%,    pre-administration of the Isoptin induced a decrease of NO content in the blood by 38% and    of Ca2+-ions content in PA by 23%, whereas endothelin content in the blood didnt change.    Pre-administration of the Plaferon LB induced a decrease of NO content in the blood by 31%, of endothelin - by 15%, and of Ca2+-ions content in PA - by 43%,    in comparison to the values of the corresponding parameters in untreated animals, under HS condition. NO plays a key role in the regulation of BAP during hypovolemia. Preparations directly or indirectly participating in the regulation of the NO synthesis can be effective in the regulation of blood pressure during hypovolemia.

Series on Biomechanics, Vol.36 No.1 (2022), 120-126
DOI: 10.7546/SB.16.2022

Keywords: blood arterial pressure; Ca2-ions; endothelin-1; Hemorrhagic shock; hypovolemia; nitric oxide (NO)

Date published: 2022-04-12