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

Abstract

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.

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

“…Although PACAP is able to exert an indirect hypertensive action mediated through the release of catecholamines (Ishizuka et al, 1992;Minkes et al, 1992a), this peptide, in very much the same way as VIP, is mainly considered as a highly potent vasorelaxant factor (Hirata et al, 1985;Ross-Ascuitto et al, 1993;Tong et al, 1993;Ascuitto et al, 1996). This vasodilatory activity, which can be ascribed at least in part to its activity on arterial smooth muscle cells Naruse et al, 1993;Steenstrup et al, 1996;Bruch et al, 1997), is well documented in various organs, including the brain (Tong et al, 1993;Anzai et al, 1995), the eye (Nilsson, 1994;Elsås and White, 1997;Dorner et al, 1998), the pulmonary vascular bed (Minkes et al, 1992b;Cheng et al, 1993;Foda et al, 1995), the mesentery (Wilson and Warren, 1993), the pancreas (Bertrand et al, 1996;Ito et al, 1998), the testis (Lissbrant et al, 1999), the ovary (Steenstrup et al, 1994;Yao et al, 1996), the vagina (Steenstrup et al, 1994;Giraldi et al, 2002;Aughton et al, 2008), the kidney (Gardiner et al, 1994), the gastrointestinal tract (Portbury et al, 1995;Badawy and Reinecke, 2003), and the skin (Wallengren, 1997).…”

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

“…The translational value of our studies awaits further investigation, as presently available data show that the vasodilator effects of PACAP depend on the pathological conditions and are different in different organs. For example, PACAP seems to play a major role in the vasodilation of meningeal arteries in migraine patients [33] and general blood flow changes upon intravenous administration [34], while its physiological role in cavernous blood vessels is questioned due to the markedly stronger effect of VIP [35]. …”

Neuropeptídeos na pele

“…82,83,84 It is also capable of stimulating the migration and proliferation of keratinocytes. 85,86,87 90,91,92,93 PACAP is liberated in the skin by cutaneous C fibers. 13 13,94,95 An intradermal injection of PACAP generates a similar progressive erythema to that produced by CGRP.…”

“…90,91,92,93 O PACAP é liberado na pele pelas fibras C cutâneas. 13 Como já citado, vários receptores interagem tanto com o PACAP quanto com o VIP, porém o receptor PACAP 1 possui grande afinidade com o primeiro.…”

“…96 A pele humana mostra-se sítio preferencial de aumento do fluxo sangüíneo na administração sistêmica de PACAP. 93 Seus efeitos nas células do sistema imune são comumente associados àqueles do VIP.…”