Thapsigargin induces an endothelium-dependent, intracellular calcium ion-dependent vasodilation in vitro.

Abstract:

:The effect of thapsigargin, a specific inhibitor of intracellular Ca(2+)-ATPases, on endothelium-dependent relaxation was studied in the guinea pig thoracic aorta. Thapsigargin (1 nM-1 microM) produced a concentration-dependent relaxation of aortic strips precontracted by phenylephrine (0.1 microM) in the presence and absence of extracellular Ca2+. Thapsigargin (0.1 microM-10 microM) produced the concentration-dependent contraction in aortic strips with no endothelium in the presence and absence of extracellular Ca2+. The relaxant effect of thapsigargin (1 microM) was not attained in a de-endothelialised aortic strip. NG-nitro-L-arginine (10 nM-0.1 mM), a blocker of NO synthase, produced a concentration-dependent inhibition of thapsigargin-induced relaxation. Thapsigargin failed to produce vasodilation by pretreatment of aortic strips with NG-nitro-L-arginine (10 microM). Thapsigargin (1 microM) increased tissue levels of guanosine 3', 5' cyclic-monophosphate in aortic strips preincubated with phenylephrine (0.1 microM). The results suggest that the intracellular Ca2+ mobilization in endothelial cells by thapsigargin is of significance in the endothelium-dependent relaxation of guinea pig thoracic aorta.

journal_name

Life Sci

journal_title

Life sciences

authors

Matsuyama S,Shuntoh H,Katayama S,Tanaka C

doi

10.1016/0024-3205(93)90244-w

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

681-8

issue

9

eissn

0024-3205

issn

1879-0631

pii

0024-3205(93)90244-W

journal_volume

53

pub_type

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