18b-glycyrrhetinic acid increases blood pressure in rats through the action on myoendothelial gap junctions

Abstract

18b-glycyrrhetinic acid (GA), a pentacyclic triterpenoid found in the roots of licorice plants (Glycyrrhiza glabra), posseses high biological activity, including anti-inflammatory and antimicrobial properties. Additionally, it effectively blocks myoendothelial gap junctions. Our experiments on adult Wistar rats have shown that GA administration via gavage in the dose 0.015 g per 100 g of body weight caused a significant increase in arterial blood pressure measured both invasively and non-invasively as early as on the 7th day after beginning of the treatment. Further administration of GA up to 21 days did not change blood pressure significantly. Thoracic aortic rings obtained from GA-treated animals demonstrated a decreased ability to relax in response to acetylcholine (ACh): the maximal dilatory response and the sensitivity of the vascular preparations to ACh measured as pD2 (-log ЕС50) were significantly suppressed compared to the relaxant responses of rings from untreated rats. GA externally applied to intact tissues at a concentration of 2×10-5 M inhibited the ACh-induced relaxation. The inhibition was more pronounced than that observed in vascular rings obtained from the GA-treated animals. Nevertheless, it was smaller than that observed under combined action of the nitric oxide synthase inhibitor, L-NAME, and indomethacin, indicating that GA affects preferentially EDHF-dependent component of the ACh-induced relaxation. These results may suggest that damage of myoendothelial gap junctions that provide electrical communication between the endothelium and the smooth muscle layers may, at least partially, cause the development of arterial hypertension under GA treatment.