PACAP-38 infusion causes sustained vasodilation of the middle meningeal artery in the rat: Possible involvement of mast cells
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PACAP-38 infusion causes sustained vasodilation of the middle meningeal artery in the rat : Possible involvement of mast cells. / Bhatt, Deepak K; Gupta, Saurabh; Olesen, Jes; Jansen-Olesen, Inger.
I: Cephalalgia : an international journal of headache, Bind 34, Nr. 11, 2014, s. 877-886.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - PACAP-38 infusion causes sustained vasodilation of the middle meningeal artery in the rat
T2 - Possible involvement of mast cells
AU - Bhatt, Deepak K
AU - Gupta, Saurabh
AU - Olesen, Jes
AU - Jansen-Olesen, Inger
N1 - © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
PY - 2014
Y1 - 2014
N2 - BACKGROUND: In healthy human volunteers and in migraineurs, pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) infusion caused sustained vasodilation of the middle meningeal artery (MMA) and an immediate as well as a delayed headache. All the study subjects experienced facial flushing. Mast cells (MCs) might have a role in the long-lasting effect of PACAP-38 infusion. We hypothesized that in mast cell-depleted (MCD) rats the vascular responses to PACAP-38 would be lesser than in control rats because of a lack of vasodilatory products released during MC degranulation.METHODS: MCs were depleted by chronic treatment with compound 48/80. The effect of 20 minutes' intravenous (i.v.) infusion of calcitonin gene-related peptide (CGRP), PACAP-38, PACAP(6-38) (PAC-1 receptor antagonist) and PACAP-27 on the diameter of the MMA and on mean arterial blood pressure (MABP) in control and MCD rats was recorded by using the genuine closed-cranial window (CCW) model. Vasoactive intestinal polypeptide (VIP) infusion was given only in control rats. A combination of the histamine H1 receptor antagonist mepyramine (4 mg kg(-1) i.v.) and the H2 receptor antagonist famotidine (1 mg kg(-1) i.v.) was given 10 minutes prior to PACAP-38 infusion. Increasing doses of PACAP-38, PACAP-27 and VIP were infused through the intracarotid artery (i.c.) in control and MCD rats to see the direct effects of these peptides on MMA diameter change.RESULTS: There was no significant change in CGRP-induced MMA diameter increase in control and MCD rats, and the dilated MMA immediately returned back to baseline after stopping the infusion. The delayed MMA dilation induced by PACAP-38 was abolished in MCD and antihistamine (AH)-pretreated rats. Compared to PACAP-38, the PACAP-27 i.v. infusion gave smaller peak dilation of MMA in control rats. In MCD rats, PACAP-27 did not induce any significant dilation. VIP i.v. infusion reduced MABP but did not dilate MMA significantly. PACAP(6-38), which is a potent MC degranulator, also gave a significant delayed dilation of MMA. PACAP-38 i.c. responses (direct receptor mediated response) were not affected by MC depletion. Only the maximum response (% E max) value of PACAP-27 (i.c.) was significantly lower in MCD rats compared to control rats.CONCLUSIONS: The delayed MMA dilatory responses to PACAP-38 infusion were attenuated in MCD and AH-pretreated rats, indicating a role of the MC mediator-histamine in PACAP-38-induced delayed dilation of MA.
AB - BACKGROUND: In healthy human volunteers and in migraineurs, pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) infusion caused sustained vasodilation of the middle meningeal artery (MMA) and an immediate as well as a delayed headache. All the study subjects experienced facial flushing. Mast cells (MCs) might have a role in the long-lasting effect of PACAP-38 infusion. We hypothesized that in mast cell-depleted (MCD) rats the vascular responses to PACAP-38 would be lesser than in control rats because of a lack of vasodilatory products released during MC degranulation.METHODS: MCs were depleted by chronic treatment with compound 48/80. The effect of 20 minutes' intravenous (i.v.) infusion of calcitonin gene-related peptide (CGRP), PACAP-38, PACAP(6-38) (PAC-1 receptor antagonist) and PACAP-27 on the diameter of the MMA and on mean arterial blood pressure (MABP) in control and MCD rats was recorded by using the genuine closed-cranial window (CCW) model. Vasoactive intestinal polypeptide (VIP) infusion was given only in control rats. A combination of the histamine H1 receptor antagonist mepyramine (4 mg kg(-1) i.v.) and the H2 receptor antagonist famotidine (1 mg kg(-1) i.v.) was given 10 minutes prior to PACAP-38 infusion. Increasing doses of PACAP-38, PACAP-27 and VIP were infused through the intracarotid artery (i.c.) in control and MCD rats to see the direct effects of these peptides on MMA diameter change.RESULTS: There was no significant change in CGRP-induced MMA diameter increase in control and MCD rats, and the dilated MMA immediately returned back to baseline after stopping the infusion. The delayed MMA dilation induced by PACAP-38 was abolished in MCD and antihistamine (AH)-pretreated rats. Compared to PACAP-38, the PACAP-27 i.v. infusion gave smaller peak dilation of MMA in control rats. In MCD rats, PACAP-27 did not induce any significant dilation. VIP i.v. infusion reduced MABP but did not dilate MMA significantly. PACAP(6-38), which is a potent MC degranulator, also gave a significant delayed dilation of MMA. PACAP-38 i.c. responses (direct receptor mediated response) were not affected by MC depletion. Only the maximum response (% E max) value of PACAP-27 (i.c.) was significantly lower in MCD rats compared to control rats.CONCLUSIONS: The delayed MMA dilatory responses to PACAP-38 infusion were attenuated in MCD and AH-pretreated rats, indicating a role of the MC mediator-histamine in PACAP-38-induced delayed dilation of MA.
U2 - 10.1177/0333102414523846
DO - 10.1177/0333102414523846
M3 - Journal article
C2 - 24563332
VL - 34
SP - 877
EP - 886
JO - Cephalalgia
JF - Cephalalgia
SN - 0800-1952
IS - 11
ER -
ID: 137619311