Effect of calcitonin gene-related peptide-induced preconditioning on attenuated endothelium-dependent vasorelaxation induced by lysophosphatidylcholine
Abstract
AIM: To study the effects of calcitonin gene-related peptide (CGRP)-induced
preconditioning on the inhibition of endothelium-dependent vasorelaxation to
acetylcholine (ACh) by lysophosphatidylcholine (Lys) in the isolated rabbit and
rat thoracic aortas.
METHODS: Endothelium-dependent relaxation to ACh was studied in the aortic rings
precontracted with phenylephrine 0.1 mumol.L-1 in the absence or presence of Lys.
RESULTS: On the rabbit aortic rings, Lys 5 mg.L-1 impaired vasodilator responses
to ACh. Pretreatment with CGRP 0.1 mumol.L-1 for 5 min attenuated the inhibition
of vasodilator responses to ACh by Lys. The effect of CGRP was blocked by
1-(5-isoquinolinysulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein
kinase C (PKC) (% relaxations to ACh 1 mumol.L-1 were 88 +/- 4, 28 +/- 10, 65 +/-
13, and 25 +/- 10 for control, Lys, Lys + CGRP, and Lys + CGRP + H-7,
respectively). The same effects of CGRP were shown in the rat aortic rings, and
the effect of CGRP was also abolished by H-7 (% relaxations to ACh 1 mumol.L-1
was 84 +/- 10, 55 +/- 11, 76 +/- 11, and 50 +/- 14 for control, Lys, Lys + CGRP,
and Lys + CGRP + H-7, respectively).
CONCLUSION: CGRP-induced preconditioning protected the endothelium against injury
elicited by Lys, the effect of CGRP is related to the activation of PKC.
Keywords:
preconditioning on the inhibition of endothelium-dependent vasorelaxation to
acetylcholine (ACh) by lysophosphatidylcholine (Lys) in the isolated rabbit and
rat thoracic aortas.
METHODS: Endothelium-dependent relaxation to ACh was studied in the aortic rings
precontracted with phenylephrine 0.1 mumol.L-1 in the absence or presence of Lys.
RESULTS: On the rabbit aortic rings, Lys 5 mg.L-1 impaired vasodilator responses
to ACh. Pretreatment with CGRP 0.1 mumol.L-1 for 5 min attenuated the inhibition
of vasodilator responses to ACh by Lys. The effect of CGRP was blocked by
1-(5-isoquinolinysulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein
kinase C (PKC) (% relaxations to ACh 1 mumol.L-1 were 88 +/- 4, 28 +/- 10, 65 +/-
13, and 25 +/- 10 for control, Lys, Lys + CGRP, and Lys + CGRP + H-7,
respectively). The same effects of CGRP were shown in the rat aortic rings, and
the effect of CGRP was also abolished by H-7 (% relaxations to ACh 1 mumol.L-1
was 84 +/- 10, 55 +/- 11, 76 +/- 11, and 50 +/- 14 for control, Lys, Lys + CGRP,
and Lys + CGRP + H-7, respectively).
CONCLUSION: CGRP-induced preconditioning protected the endothelium against injury
elicited by Lys, the effect of CGRP is related to the activation of PKC.