Vasorelaxant effect of PACAP-27 on canine cerebral arteries and rat intracerebral arterioles

Anzai, Masaoki; Suzuki, Yoshio; Takayasu, Misako; Kajita, Yasukazu; Mori, Yoshimasa; Seki, Yukio; Saito, Kiyoshi; Shibuya, Masabumi

doi:10.1016/0014-2999(95)00404-9

Cited by 31 publications

(17 citation statements)

References 41 publications

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“…These diverse functions also include potent vasomotor effects [17,18]. There are studies showing relaxations to both PACAP isoforms and VIP in vessels of different origin, such as carotid [23], pulmonary [24], mesenteric and coronary [38], meningeal [20], cerebral and intracerebral [21,22], and middle cerebral arteries [10] of various species. Similarly, we also observed relaxations, which were significantly greater in response to PACAP1-38 as compared to PACAP1-27 and VIP in both arteries of WT mice.…”

Section: Discussionmentioning

confidence: 99%

“…The vasodilator activity of PACAP has been recorded in vessels of various organs in mice [20], rats [21,22,23], cats [15,24], rabbits [25], dogs [21], pigs [18], and humans [26]. These actions are mediated through all 3 PACAP receptors, which are highly expressed (alone/combined or all together) in the aorta [27], mesenteric [25], coronary [28], cranial arteries [10], pulmonary vascular bed [15], and many other blood vessels [1,29].…”

Section: Introductionmentioning

confidence: 99%

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Backup Mechanisms Maintain PACAP/VIP-Induced Arterial Relaxations in Pituitary Adenylate Cyclase-Activating Polypeptide-Deficient Mice

Ivić

Fülöp²,

Juhász

et al. 2017

J Vasc Res

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Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multifunctional neuropeptide in the VIP/secretin/glucagon peptide superfamily. Two active forms, PACAP1-38 and PACAP1-27, act through G protein-coupled receptors, the PAC1 and VPAC1/2 receptors. Effects of PACAP include potent vasomotor activity. Vasomotor activity and organ-specific vasomotor effects of PACAP-deficient mice have not yet been investigated; thus, the assessment of its physiological importance in vasomotor functions is still missing. We hypothesized that backup mechanisms exist to maintain PACAP pathway activity in PACAP knockout (KO) mice. Thus, we investigated the vasomotor effects of exogenous vasoactive intestinal peptide (VIP) and PACAP polypeptides in PACAP wild-type (WT) and PACAP-deficient (KO) male mice. Methods: Carotid and femoral arteries were isolated from 8- to 12-week-old male WT and PACAP-KO mice. Vasomotor responses were measured with isometric myography. Results: In the arteries of WT mice the peptides induced relaxations, which were significantly greater to PACAP1-38 than to PACAP1-27 and VIP. In KO mice, PACAP1-38 did not elicit relaxation, whereas PACAP1-27 and VIP elicited significantly greater relaxation in KO mice than in WT mice. The specific PAC1R and VPAC1R antagonist completely blocked the PACAP-induced relaxations. Conclusion: Our data suggest that in PACAP deficiency, backup mechanisms maintain arterial relaxations to polypeptides, indicating an important physiological role for the PACAP pathway in the regulation of vascular tone.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Backup Mechanisms Maintain PACAP/VIP-Induced Arterial Relaxations in Pituitary Adenylate Cyclase-Activating Polypeptide-Deficient Mice

Ivić

Fülöp²,

Juhász

et al. 2017

J Vasc Res

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“…While vasodilating properties of PACAP were found in vitro and in vivo in animals (Uddman et al 1993;Anzai et al 1995;Seki et al 1995), the role of PACAP as a regulator of cerebral vascular tone has not yet been studied in humans. Surprisingly, in our experiments we did not observe changes in cerebral blood flow velocity in the middle cerebral artery.…”

Section: Discussionmentioning

confidence: 99%

Effect of pituitary adenylate cyclase activating polypeptide 1–27 on ocular, cerebral and skin blood flow in humans

Dorner¹,

Wolzt²,

Schmetterer³

et al. 1998

Naunyn-Schmiedeberg's Arch Pharmacol

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The aim of the study was to assess the effects of a neuropeptide, pituitary adenylate cyclase activating polypeptide 1-27 (PACAP), on ocular, cerebral and skin blood flow in man. PACAP (0.01-10 pmol kg(-1) min(-1)) was administered intravenously to eight healthy male subjects in a placebo-controlled, double-blind dose escalation trial. Fundus pulsation amplitude was measured by laser interferometry, mean blood flow velocity in the ophthalmic artery and the middle cerebral artery measured by Doppler sonography, and regional blood flow of the skin was estimated by laser Doppler flowmetry. Infusion of PACAP at the highest dose of 10 pmol kg(-1) min(-1) induced a significant increase in fundus pulsation amplitude (+83.4%), mean flow velocity in the ophthalmic artery (+91.9%) and regional skin blood flow (+260.3%, P<0.01, ANOVA; each parameter). In contrast, PACAP did not cause any change in middle cerebral artery blood flow velocity or systemic hemodynamics. Our findings indicate that the vasculatures of the eye and the skin are particularly sensitive to PACAP and may implicate a potential role for this peptide in the regulation of blood flow in these vascular beds.

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“…However, it seems that there is no general rule concerning the potency of PACAP peptides and VIP in the vasculature. Previous studies showed vasodilatory effects of PACAP and VIP in different vessels of different regions, such as the brain [7,8,9,10,23,25], abdominal cavity [23], lung [23,24], and limbs [7] of various species.…”

Section: Discussionmentioning

confidence: 99%

“…For example, infusion of PACAP1-38, PACAP1-27, or VIP (0.25-25 pmol/kg) in dog femoral arteries induces a concentration-dependent increase in blood flow [6]. The vasodilator activity of PACAP has also been recorded in vitro in vessels of various organs of mice [7,8], rats [9,10,11], rabbits [12], pigs [5], and humans [13]. …”

Section: Introductionmentioning

confidence: 99%

Aging-Induced Modulation of Pituitary Adenylate Cyclase-Activating Peptide- and Vasoactive Intestinal Peptide-Induced Vasomotor Responses in the Arteries of Mice

Ivić¹,

Solymár

Fülöp³

et al. 2017

J Vasc Res

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Pituitary adenylate cyclase-activating peptide (PACAP; 1-38 and 1-27) and vasoactive intestinal peptide (VIP) are related neuropeptides of the secretin/glucagon family. Overlapping signaling through G-protein-coupled receptors mediates their vasomotor activity. We previously showed that PACAP deficiency (PACAP-KO) shifts the mechanisms of vascular response and maintains arterial relaxation through the VIP backup mechanism and (mainly) its VPAC1R, but their age-dependent modulation is still unknown. We hypothesized that backup mechanisms exist, which maintain the vasomotor activity of these peptides also in older age. Thus, we investigated the effects of exogenous VIP and PACAP peptides in isolated carotid arteries of 2- and 15-month-old wild-type (WT) and PACAP-KO mice. All peptides induced relaxation in the arteries of young WT mice, whereas in young PACAP-KO mice PACAP1-27 and VIP, but not PACAP1-38, induced relaxation. Unlike VIP, PACAP-induced vasomotor responses were reduced in aging WT mice. However, in the arteries of aging PACAP-KO mice, PACAP1-27- and VIP-induced responses were reduced, but PACAP1-38 showed a greater vasomotor response compared to that of young PACAP-KO animals. There were no significant differences between the vasomotor responses of aging WT and PACAP-KO mice. Our data suggest that, in the absence of PACAP both in young and old ages, the vascular response is mediated through backup mechanisms, most likely VIP, maintaining proper vascular relaxation in aging-induced PACAP insufficiency.

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Vasorelaxant effect of PACAP-27 on canine cerebral arteries and rat intracerebral arterioles

Cited by 31 publications

References 41 publications

Backup Mechanisms Maintain PACAP/VIP-Induced Arterial Relaxations in Pituitary Adenylate Cyclase-Activating Polypeptide-Deficient Mice

Backup Mechanisms Maintain PACAP/VIP-Induced Arterial Relaxations in Pituitary Adenylate Cyclase-Activating Polypeptide-Deficient Mice

Effect of pituitary adenylate cyclase activating polypeptide 1–27 on ocular, cerebral and skin blood flow in humans

Aging-Induced Modulation of Pituitary Adenylate Cyclase-Activating Peptide- and Vasoactive Intestinal Peptide-Induced Vasomotor Responses in the Arteries of Mice

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