Characterization of a novel tetrandrine-induced contraction in rat tail artery

Abstract

Aim: In an attempt to pharmacologically characterize the Chinese antihypertensive drug, tetrandrine, we observed in rat-tail arteries, an unusual contraction in tissues that were stimulated with high [KCl] and not those stimulated with phenylephrine. The characteristics of this contraction were studied.

Methods: Segments of perfused ventral rat-tail arteries (RTA) were contracted with a depolarizing concentration (120 mmol/L) of KCl or with phenylephrine (3.0 micromol/L). At peak contraction, they were exposed to tetrandrine (40 micromol/L), which caused marked relaxation in each case. Washing the RTA led to an unusual, slowly-declining contraction, hereafter referred to as tetrandrine-induced contraction (TIC) which was also observed when the tissues were exposed to 80 micromol/L, but not 10 micromol/L or 20 micromol/L of tetrandrine.

Results: Pretreatment with phentolamine (non-selective alpha-adrenoceptor antagonist), prazosin (selective alpha1-adrenoceptor antagonist) or 6-hydroxydopamine (for denervation), but not rauwolscine or atropine abolished the TIC. Treatment with ouabain (Na+/K+-ATPase inhibitor) did not sustain the contraction. Changing the depolarizing concentrations of KCl to 80 mmol/L or 100 mmol/L did not alter the TIC, but at 60 mmol/L, it was abolished.

Conclusion: The data show that tetrandrine induces a K+-dependent contraction of the RTA through a neuronal mechanism involving alpha1-adrenoceptors. It is speculated that this contraction may be a factor in the reported absence of postural hypotension in the clinical use of tetrandrine.