NMDA antagonists attenuate baroreflex in the rostral ventrolateral medulla of rats

Abstract

A large scale screening test of the vasorelaxing actions of the extracts from Chinese herbs has been performed and the active principles were isolated: osthole from Angelica pubescens, protopine from Corydalis tubers, norathyriol from Gentianaceae, denudatin B and fargesone B from Magnolia fargesii, apigenin from Apium graveolens, and magnolol from Magnolia officinales. In this experiment, we tried to study the effects of these Chinese herbal principles on the vasoconstriction of rat thoracic aorta induced by high potassium solution, norepinephrine (NE) and caffeine, and to elucidate their modes of action. All the seven principles suppressed the contraction of rat thoracic aortic rings caused by cumulative concentrations of calcium (0.03-3 mM) in high potassium (60 mM) medium. They also relaxed the NE (3/tM)-induced contraction, and their pretreatment inhibited both the phasic and tonic contractions elicited by NE in the absence or presence of calcium (1.9 raN) in the medium. Indomethacin (20 pM) did not have any antagonizing effect on these relaxations. Osthole and magnolol also inhibited caffeine (I0 mM)-induced phasic contraction, while others did not have any effect. In quin-2-1oaded cultured rat vascular smooth muscle cells, NE-induced rises of intracellular calcium were suppressed by denudatin B and fargesone B. '~SCa++ uptakes induced by either NE or high potassium were inhibited by the seven vasorelaxants in a concentration-dependent manner. All these vasorelaxants did not change the levels of prostacyclin or cAMP of rat aorta. Both osthole and magnolol caused formation of cGMP in aorta, while other vasorelaxants did not have any effect or were effective only at higher concentrations than those relaxing the mu~!eo The cGMP increase and initial relaxation caused by magnolol were disappeared after the aorta was denuded. This endothelium-dependent relaxation by magnolol was antagonized by methylene blue (50/~M) and hemoglobin (10/~M) which were known to inhibit activation of guanylate cyclase and inactivate endothelium-derived relaxing factor (EDRF), respectively. in conclusion, seven vasorelaxants isolated from Chinese herbs inhibited vascular muscle contraction of rat aorta by suppressing the calcium i~flux through both voltage-gated and receptor-operated calcium channels. EDRE release by magnolol and cGMP increase by osthole may enhance their relaxing effects in rat aorta.