Pituitary Adenylate Cyclase Activating Peptides are Endothelium-Independent Dilators of Human and Porcine Coronary Arteries

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Induces Relaxations of Peripheral and Cerebral Arteries, which are Differentially Impaired by Aging

“…Others have found similar results: PACAP1-38 elicits relaxant effect on rabbit aorta and mesenteric arteries, and also on human and porcine coronary arteries (Warren et al 1991 ;Kastner et al 1995 ). Comparing the magnitude of relaxation within a single species (rabbit), more prominent response was found in the macrovessels than the microcirculation (Wilson and Warren 1993 ).…”

“…A previous study (Erdling et al 2013 ) suggests that activation is via the stimulation of cAMP production in blood vessels, which modulates L-type calcium channels in vascular smooth muscle cells through the activation of both protein kinase A (PKA) and protein kinase C (PKC) mechanisms resulting in vasodilation (Chik et al 1996 ). PACAP also stimulates the release of the prostaglandin PGF in the wall of the arteries but does not affect other cyclooxygenase metabolites (Huang et al 1992 ;Kastner et al 1995 ). Others found that PACAP relaxes human pulmonary arteries by opening of KATP and KCa channels (Bruch et al, 1998).The possible involvement of the endothelium in the vasodilator activity of PACAP is still not clear: Some reports indicate that the relaxant effect of PACAP on the rabbit aorta and coronary arteries is endothelium-independent (Warren et al 1991 ;Kastner et al 1995 ), whereas another study reveals that removal of the vascular endothelium abolishes the dilatorydilator response induced by PACAP in guinea pig pulmonary arteries (Cardell et al 1991 ).…”

“…PACAP also stimulates the release of the prostaglandin PGF in the wall of the arteries but does not affect other cyclooxygenase metabolites (Huang et al 1992 ;Kastner et al 1995 ). Others found that PACAP relaxes human pulmonary arteries by opening of KATP and KCa channels (Bruch et al, 1998).The possible involvement of the endothelium in the vasodilator activity of PACAP is still not clear: Some reports indicate that the relaxant effect of PACAP on the rabbit aorta and coronary arteries is endothelium-independent (Warren et al 1991 ;Kastner et al 1995 ), whereas another study reveals that removal of the vascular endothelium abolishes the dilatorydilator response induced by PACAP in guinea pig pulmonary arteries (Cardell et al 1991 ). More importantly, the effect of age on the PACAPinduced vasomotor responses are not known.…”

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

“…PACAP can also increase the amplitude of L-type Ca 2ϩ channel currents in vascular smooth muscle cells through the activation of both PKA, PKC, and PLC (Chik et al, 1996;Markhotina et al, 2007) with a greater efficiency in spontaneously hypertensive rats than in normotensive animals (Li et al, 2001). The involvement of the endothelium in the vasodilatory activity of PACAP is still a matter of debate: two reports indicate that the vasorelaxant effect of PACAP on the aorta and coronary arteries is endothelium-independent (Warren et al, 1991;Kä stner et al, 1995), whereas another study reveals that removal of the vascular endothelium abolishes the dilatory response induced by PACAP in pulmonary arteries . Finally, some of the effects of PACAP on the vascular bed appears to be mediated through the release of vasculotropic factors.…”

Pituitary Adenylate-Cyclase-Activating Peptides Relax Human Coronary Arteries by Activating K_ATP and K_Ca Channels in Smooth Muscle Cells

“…cats [5], sheep [6] and dogs [7], the PACAPs cause systemic vasodilation accompanied by an increase in heart rate in vivo. Our previous studies have demonstrated that PACAP27 and PACAP38 are potent dilators of isolated human and porcine epicardial coronary arteries [8], In porcine coronary arteries, the PACAPs' relaxant effects were not influenced by removal of the endothelium, sug-gcstingan endothelium-independent vasodilatory mecha nism [8], which has also been shown in rabbit aorta [2], The membrane potential of arterial smooth muscle cells, which is regulated by K+ channels, is an important regulator of arterial tone and hence arterial diameter. The opening of K+ channels in the cell membrane of smooth muscle cells increases K+ efflux, which causes hypcrpolarization of membrane potential.…”