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


CONCLUSIONS
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.
Achike
Francis Ifejika
FI
Clinical Sciences Section, International Medical University, Kuala Lumpur, Malaysia.
Kwan
Chiu-Yin
CY
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000502:physiology; D044182:Benzylisoquinolines; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine; D011189:Potassium Chloride; D051381:Rats; D017207:Rats, Sprague-Dawley; D013623:Tail / Q000098:blood supply
D000470:Alkaloids; D044182:Benzylisoquinolines; D010656:Phenylephrine; C009438:tetrandrine; D011189:Potassium Chloride