Differential effects of PACAP and VIP on the pulmonary and hindquarters vascular beds of the cat

Minkes, Robert K.; McMahon, Timothy J.; Hood, J. S.; Murphy, William A.; Coy, David H.; McNamara, Dennis B.; Kadowitz, Philip J.

doi:10.1152/jappl.1992.72.3.1212

Cited by 38 publications

(19 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[7][8][9][10] Our own preliminary experiments confirmed vasodilatory effects of PACAP on murine pulmonary arteries (L. Hein, unpublished data). Although PAC1 mRNA is expressed in lungs, 5,18 it was not possible to unravel the cellular localization of PAC1 protein in lungs 4 (C. Otto, unpublished data).…”

Section: Discussionsupporting

confidence: 66%

“…4 PACAP-positive nerve fibers have been found among smooth muscle bundles in tracheal and bronchial walls and around small blood vessels. 6 PACAP as well as VIP exerts dilatory effects on pulmonary blood vessels [7][8][9][10] and bronchi. 9 -11 In contrast to the effects of VIP, PACAPinduced dilation of pulmonary arteries depends on an intact endothelium and can be blocked by nitric oxide synthase inhibitors.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Pulmonary Hypertension and Right Heart Failure in Pituitary Adenylate Cyclase–Activating Polypeptide Type I Receptor–Deficient Mice

et al. 2004

View full text Add to dashboard Cite

Background-Pituitary adenylate cyclase-activating polypeptide (PACAP), acting via 3 different G protein-coupled receptors, has been implicated in the regulation of several homeostatic systems in the body, including cardiopulmonary control. To define the physiologic role of the PACAP-preferring type I receptor, PAC1, in cardiopulmonary function, we developed a mutant mouse strain lacking functional PAC1 receptors. Methods and Results-When PAC1-deficient mice were crossed onto a C57BL/6 background, almost all mutants died during the second postnatal week. Whereas mutant mice were indistinguishable from their wild-type littermates at birth, they showed progressive weakness and died from rapidly developing heart failure. Right ventricles of PAC1 mutants were massively dilated and showed cardiac myocyte hypertrophy, whereas left ventricular structure was unaltered. On direct cardiac catheterization, right ventricular pressure was elevated by 45% in PAC1-deficient mice, indicating increased pulmonary artery pressure, as no malformations were detected in the valves or outflow tract of the right ventricle. Consistent with elevated pulmonary pressure, lung capillary density was decreased by 30% and small pulmonary arteries of mutant mice had significant vascular smooth muscle cell hypertrophy compared with wild-type mice. Conclusions-Whereas PACAP induces vasodilation in isolated pulmonary vessels in wild-type mice, the absence of its specific receptor PAC1 causes pulmonary hypertension and right heart failure after birth. These in vivo findings demonstrate the crucial importance of PAC1-mediated signaling for the maintenance of normal pulmonary vascular tone during early postnatal life.

show abstract

Section: Discussionsupporting

confidence: 66%

mentioning

confidence: 99%

Pulmonary Hypertension and Right Heart Failure in Pituitary Adenylate Cyclase–Activating Polypeptide Type I Receptor–Deficient Mice

et al. 2004

View full text Add to dashboard Cite

show abstract

“…These doses of PACAP were chosen so dP/dt,,, and vascular tone would return to near baseline levels on washout of the hormone. Similar doses of PACAP also have been shown to evoke vasoactive effects in the pulmonary and systemic (hindquarter) vascular beds of cats (10). In four of the experiments, the 0.1-nmol dose of PACAP was administered first, followed by the 0.5-nmol dose.…”

mentioning

confidence: 86%

“…Isoproterenol (n = 5, 0.1 and 0.5 nmol) increased PACAP in vascular beds of intact organs (9). Recently, Minkes (+) dp1dtma, from 793 51 to 1343 + 75 mm ~g /~ ( p = ef (10) VIP, have been demonstrated in the myocardium and coronary duced positive inotropic, luisitropic, and coronary vasodil-arteries of several adult species (12). The present study, therefore, effects in piglet which may make a was undertaken to investigate the effects of PACAP on contractile promising cardiOtOnic agent for the treatment function and coronary vascular tone using neonatal pig hearts.…”

mentioning

confidence: 96%

Pituitary Adenylate Cyclase Activating Polypeptide: A Neuropeptide with Potent Inotropic and Coronary Vasodilatory Effects in Neonatal Pig Hearts

et al. 1993

View full text Add to dashboard Cite

ABSTRACT. Cardiac effects of the neuropeptide pituitaryAbbreviations adenylate cyclase activating p o l y p e p t i d e -(~~~i~) have not previously been reported. W e investigated the influence of PACAP, vasoactive intestinal polypeptide (68% homology with PACAP) and the B-adrenergic receptor agonist isoproterenol on contractile function and coronary vascular tone in isolated piglet hearts (1 to 5 d of age). Paced (180 beatslmin) isovolumically beating hearts underwent retrograde aortic perfusion a t constant coronary flow (approximately 3 mL. min-' . g-') with an erythrocyte-enriched PACAP, pituitary adenylate cyclase activating polypeptide VIP, vasoactive intestinal polypeptide ISP, isoproterenol IBMX, isobutylmethylxanthine dP/dt,,, maximum rate of change of systolic pressure with respect to time (+), positive (-), negative (hematocrit 15 to 20%)~solution ( 3 7 "~) . ~g o n i s t s were injected into the aortic root of hearts, and the positive (+) and negative (-) changes in maximum rate of change of systolic pressure with respect to time (dP/dtma,) and in PACAP is a newly discovered neuropcptide isolated from the coronary perfusion pressure (that reflected alterations in ovine hypothalamus (1). PACAP is present in two forms: one vascular tone) were measured. PACAP (n = 8,O.l and 0.5 with 27 and the other with 38 N-terminal amino acid residues nmol) increased (+) dP/dt,, from 944 + 59 to 1519 f 206 (2). PACAP has a 68% sequence homology with VIP and appears mm ~g / s and from 867 2 40 to 2010 +: 226 mm ~g / s ( p to be more potent than VIP in stimulating adenylate cyclase in < 0.05); increased (-1 dpldt,, from 11 14 41 to 14-39 + pituitary cells (2). PACAP also has been shown to increase cAMP 9 5 mm ~g and from 999 f 37 to 1668 + 145 mm H~/ S levels in the human neuroblastoma cell line NB-OK (3), the rat ( p < 0.05); and decreased perfusion pressure from 61.4 2 pancreatic acinar cell line AR 4-25 (4), and rat liver cell mem-3.1 to 48.9 2 2.3 mm 1 1~ and from 60.5 + 2.4 to 43.9 branes ( 5 ) . Moreover, high affinity binding sites for PACAP have 2.3 mm H~ (p < 0.05), respectively. comparison, vase-been identified in several organ systems, including the rat lung active intestinal polypeptide (n = 6, 0.1 and 0.5 nmol) (6) and h m a n brain (7). increased (+) dP/dtmn, from 767 +. 53 to 806 + 37 mm Hg/ The ~h~s i o l o g i c role of PACAP has not been elucidated, and from 829 2 94 to 942 8 5 mm ~g /~ (NS); increased although it has been suggested that this peptide may be involved (-) dp/dtma, from 883 2 73 to 926 45 ,,,,,, ~g /~ and in the regulation of vascular smooth muscle tone, in addition to from 923 + 8 2 to 1054 f 78 mm Hg/s (NS); and decreased its presumed role as a hypothalamic, hypophysiotropic hormone perfusion pressure from 57.9 + 4.9 to 50.0 +. 3.6 mm H~ (8 VIP, have been demonstrated in the myocardium and coronary duced positive inotropic, luisitropic, and coronary vasodil-arteries of several adult species (12). The present study, therefore, effects in piglet which may make a was undertaken to inv...

show abstract

“…VIP has been reported to promote the relaxation of vascular smooth muscle cells (3); to inhibit the proliferation of pulmonary arterial smooth muscle cells in vitro (4); to reduce pulmonary vasoconstriction induced by endothelin or hypoxia (5,6); and to present with antithrombotic effects (7). The cotransmitter PACAP also demonstrates actions similar to VIP on the pulmonary vasculature, such as vasodilation and inhibition of vascular remodeling (8).…”

mentioning

confidence: 99%

Expression of Vasoactive Intestinal Peptide and Related Receptors in Overcirculation-Induced Pulmonary Hypertension in Piglets

et al. 2009

View full text Add to dashboard Cite

ABSTRACT:The pathobiology of pulmonary arterial hypertension (PAH) is not understood completely. Recent observations in patients with PAH and in knockout models have raised the idea that a defect in vasoactive intestinal peptide (VIP) may be involved in PAH physiopathology. Therefore, we investigated the expressions of VIP, the related pituitary adenylate cyclase-activating polypeptide (PACAP), and their receptors (VPAC 1 , VPAC 2 , and PAC 1 ) in piglets with overcirculation-induced pulmonary hypertension as an earlystage PAH model. Seventeen piglets were randomized to an anastomosis between the innominate and the main pulmonary artery, or to a sham operation. After 3 mo, a hemodynamic evaluation was performed and the lung tissue was sampled for biologic and histologic studies. The shunting increased pulmonary vascular resistance (PVR) by 100% and arteriolar medial thickness by 85%. VIP and VPAC 1 gene expressions were decreased and increased, respectively. VPAC 1 gene expression was positively correlated to PVR. VPAC 2 and PAC 1 immunoreactivity was seen in pulmonary arterial smooth muscle. VIP and PACAP immunostaining was observed in nerve fibers surrounding the pulmonary arterial smooth muscle. In conclusion, overcirculation-induced pulmonary hypertension is accompanied by a down-regulation of VIP signaling, without change in PACAP expression. These results are consistent with the notion that abnormal VIP signaling takes part in PAH pathogenesis. (Pediatr Res 66: 395-399, 2009) T he pathobiology of pulmonary arterial hypertension (PAH) is complex and is not understood completely (1). Several abnormal signaling pathways have been identified, involving the three layers of the pulmonary arterial walls, but their respective roles in initiating or perpetuating the disease remain undefined (1).Recent observations have drawn attention to a possible implication of the vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) systems. VIP belongs to a family of structurally related hormones, including the PACAP. PACAP exists in two forms in mammals (PACAP 27 and PACAP 38 ), derived from the same precursor. These ubiquitous and homologous neuropeptides share pleiotropic functions and display highly preserved genes during evolution, suggesting their involvement in important physiologic mechanisms (2). Their actions are mediated through interaction with G-protein-coupled receptors (VPAC 1 , VPAC 2 , and PAC 1 ): PAC 1 receptors have greater affinity for PACAP than for VIP, whereas VPAC receptors bind both the peptides with comparable affinity (2). VIP has been reported to promote the relaxation of vascular smooth muscle cells (3); to inhibit the proliferation of pulmonary arterial smooth muscle cells in vitro (4); to reduce pulmonary vasoconstriction induced by endothelin or hypoxia (5,6); and to present with antithrombotic effects (7). The cotransmitter PACAP also demonstrates actions similar to VIP on the pulmonary vasculature, such as vasodilation and inhibition of vascular re...

show abstract

Differential effects of PACAP and VIP on the pulmonary and hindquarters vascular beds of the cat

Cited by 38 publications

References 0 publications

Pulmonary Hypertension and Right Heart Failure in Pituitary Adenylate Cyclase–Activating Polypeptide Type I Receptor–Deficient Mice

Pulmonary Hypertension and Right Heart Failure in Pituitary Adenylate Cyclase–Activating Polypeptide Type I Receptor–Deficient Mice

Pituitary Adenylate Cyclase Activating Polypeptide: A Neuropeptide with Potent Inotropic and Coronary Vasodilatory Effects in Neonatal Pig Hearts

Expression of Vasoactive Intestinal Peptide and Related Receptors in Overcirculation-Induced Pulmonary Hypertension in Piglets

Contact Info

Product

Resources

About