Effects of thapsigargin in isolated rat thoracic aorta
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Effects of thapsigargin in isolated rat thoracic aorta. / Mikkelsen, E O; Thastrup, Ole; Christensen, S B.
In: Pharmacology & Toxicology, Vol. 62, No. 1, 1988, p. 7-11.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Effects of thapsigargin in isolated rat thoracic aorta
AU - Mikkelsen, E O
AU - Thastrup, Ole
AU - Christensen, S B
PY - 1988
Y1 - 1988
N2 - The effect of thapsigargin (Tg) was studied in rat thoracic aorta. Tg (10(-8)-10(-5) M) had a dual effect on rat aorta. Thus, Tg induced a concentration dependent increase in basal tone in normal physiological salt solution (PSS), while Tg in potassium (K+) precontracted aortic rings caused a concentration related relaxation and shifted the K+-concentration response curve to the right and depressed the maximal response to K+. Removal of vascular endothelium abolished the relaxant response to Tg and increased the sensitivity of the preparations to the contractile effect of Tg. The contractile response to Tg was resistent to wash-out in drug-free PSS and was not affected by phentolamine, indomethacin or mepyramine but partly reduced by the calcium-antagonist nitrendipine and eliminated by wash-out in calcium-free PSS. Atropine eliminated the endothelium dependent relaxant effect of carbachol, but had no effect on the Tg or on the calcium ionophore A 23187 evoked relaxation. Ultraviolet radiation decreased the relaxant effect of Tg and A 23187 without affecting the carbachol induced relaxations. The results showed that vascular endothelium depressed the contractile effect of Tg and that Tg like A 23187 had an endothelium dependent relaxant effect on rat aorta different from that of carbachol. The results indicate that Tg in vascular smooth muscle acts by stimulating the transmembranal influx of extracellular calcium.
AB - The effect of thapsigargin (Tg) was studied in rat thoracic aorta. Tg (10(-8)-10(-5) M) had a dual effect on rat aorta. Thus, Tg induced a concentration dependent increase in basal tone in normal physiological salt solution (PSS), while Tg in potassium (K+) precontracted aortic rings caused a concentration related relaxation and shifted the K+-concentration response curve to the right and depressed the maximal response to K+. Removal of vascular endothelium abolished the relaxant response to Tg and increased the sensitivity of the preparations to the contractile effect of Tg. The contractile response to Tg was resistent to wash-out in drug-free PSS and was not affected by phentolamine, indomethacin or mepyramine but partly reduced by the calcium-antagonist nitrendipine and eliminated by wash-out in calcium-free PSS. Atropine eliminated the endothelium dependent relaxant effect of carbachol, but had no effect on the Tg or on the calcium ionophore A 23187 evoked relaxation. Ultraviolet radiation decreased the relaxant effect of Tg and A 23187 without affecting the carbachol induced relaxations. The results showed that vascular endothelium depressed the contractile effect of Tg and that Tg like A 23187 had an endothelium dependent relaxant effect on rat aorta different from that of carbachol. The results indicate that Tg in vascular smooth muscle acts by stimulating the transmembranal influx of extracellular calcium.
KW - Animals
KW - Aorta, Thoracic
KW - Calcimycin
KW - Carbachol
KW - Endothelium, Vascular
KW - Male
KW - Muscle Contraction
KW - Muscle, Smooth, Vascular
KW - Plant Extracts
KW - Potassium
KW - Rats
KW - Rats, Inbred Strains
KW - Thapsigargin
M3 - Journal article
C2 - 3128782
VL - 62
SP - 7
EP - 11
JO - Pharmacology and Toxicology
JF - Pharmacology and Toxicology
SN - 0901-9928
IS - 1
ER -
ID: 43350347