An aqueous extract of Zanthoxylum schinifolium has a positive inotropic effect in beating rabbit atria

Abstract

The positive inotropic effect of the aqueous extract of Zanthoxylum schinifolium (AZS) and the possible mechanisms responsible for this effect were investigated in beating rabbit atria. AZS significantly increased atrial stroke volume, pulse pressure, and cAMP efflux, but decreased ANP secretion in beating rabbit atria. These effects were restricted by pre‐treatment with diltiazem or veraparmil, L‐type Ca2+ channel blockers, and staurosporine, a non‐selective protein kinase inhibitor, respectively. The effects of AZS on atrial dynamics were also abolished by pre‐treatment with KT‐5720, a protein kinase A inhibitor, but was not altered by treatment of chelerythrine, a protein kinase C inhibitor. Treatment of atrial membrane with AZS obviously increased the cAMP production induced by forskolin, but not increased by 3‐isobutyl‐1‐methylxanthine (IBMX). Furthermore, co‐treatment with AZS and Ro 20‐1724, a phosphodiesterase (PDE)‐4 inhibitor, more produced atrial cAMP than Ro 20‐1724 alone. However, there were no increase in atrial cAMP production by co‐treatment with AZS and milrinone, a PDE‐3 inhibitor, compared with milrinone alone. These results suggest that the AZS‐induced positive inotropic activity may be due to the enhancement of cAMP level by PDE‐3 inhibition in beating rabbit atria.