Distribution Of Vasoactive Intestinal Polypeptide Research Articles

Expression of VPAC1 receptor at the level of mRNA and protein in the porcine female reproductive system.

The presence and distribution of vasoactive intestinal polypeptide (VIP) receptor VPAC1 was studied in the ovary, oviduct and uterus (uterine horn and cervix) of the domestic pig using methods of molecular biology (RT-PCR and immunoblot) and immunohistochemistry. The expression of VPAC1 receptor at mRNA level was confirmed with RT-PCR in all the studied parts of the porcine female reproductive system by the presence of 525 bp PCR product and at the level of proteins by the detection of 46 kDa protein band in immunoblot. Immunohistochemical stainings revealed the cellular distribution of VPAC1 receptor protein. In the ovary it was present in the wall of arterial blood vessels, as well as in the ovarian follicles of different stages. In the tubular organs the VPAC1 receptor immunohistochemical stainings were observed in the wall of the arterial blood vessels, in the muscular membrane, as well as in the mucosal epithelium. The study confirmed the presence of VPAC1 receptor in the tissues of the porcine female reproductive tract what clearly shows the possibility of influence of VIP on the porcine ovary, oviduct and uterus.

Long-term dietary l-arginine supplementation increases endothelial nitric oxide synthase and vasoactive intestinal peptide immunoexpression in rat small intestine

Nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) are important intestinal neurotransmitters that coexist in the gut enteric nervous system and play an important role in intestinal physiology (e.g., absorption, motility, fluid secretion and smooth muscle relaxation). It is also known that cold exposure alters several aspects of gastrointestinal physiology and induces hyperphagia to meet increased metabolic demands, but there are no data regarding NO and VIP involvement in intestinal response during acclimation to cold. The objective of this study was to determine the influence of long-term L-arginine supplementation on the expression of the three isoforms of nitric oxide synthase (NOS) and VIP in small intestine of rats acclimated to room temperature or cold. Animals (six per group) acclimated to room temperature (22 ± 1 °C) and cold (4 ± 1 °C), respectively, were treated with 2.25% L-arginine, a substrate for NOSs, or with 0.01% N(ω)-nitro-L-arginine methyl ester, an inhibitor of NOSs, for 45 days. The topographical distribution of VIP and NOSs expression in small intestine was studied by immunohistochemistry, and ImageJ software was used for semiquantitative densitometric analysis of their immunoexpression. Long-term dietary L-arginine supplementation increases VIP and NOSs immunoexpression at room temperature while at cold increases the endothelial NOS, inducible NOS and VIP but decrease neuronal NOS in rat small intestine. Our results demonstrate that long-term dietary L-arginine supplementation modulates NOSs and VIP immunoexpression in rat small intestine with respect to ambient temperature, pointing out the eNOS as a predominant NOS isoform with an immunoexpression pattern similar to VIP.

Immunohistochemical characterization and quantitative analysis of neurons in the myenteric plexus of the equine intestine

The present study was performed on whole-mount preparations to investigate the chemical neuroanatomy of the equine myenteric plexus throughout its distribution in the intestinal wall. The objective was to quantify neurons of the myenteric plexus, especially the predominant cholinergic and nitrergic subpopulations. Furthermore, we investigated the distribution of vasoactive intestinal polypeptide and the calcium-binding protein calretinin. Samples from different defined areas of the small intestine and the flexura pelvina were taken from 15 adult horses. After fixation and preparation of the tissue, immunofluorescence labeling was performed on free floating whole-mounts. Additionally, samples used for neuropeptide staining were incubated with colchicine to reveal the neuropeptide distribution within the neuronal soma. The evaluation was routinely accomplished using confocal laser-scanning microscopy. For quantitative and qualitative analysis, the pan-neuronal marker anti-HuC/D was applied in combination with the detection of the marker enzymes for cholinergic neurons and nitrergic nerve cells. Quantitative data revealed that the cholinergic subpopulation is larger than the nitrergic one in several different locations of the small intestine. On the contrary, the nitrergic neurons outnumber the cholinergic neurons in the flexura pelvina of the large colon. Furthermore, ganglia are more numerous in the small intestine compared with the large colon, but ganglion sizes are bigger in the large colon. However, comparison of the entire population of neurons in the different locations of the gut showed no difference. The present study adds further data on the chemoarchitecture of the myenteric plexus which might facilitate the understanding of several gastrointestinal disorders in the horse.

Distribution of vasoactive intestinal polypeptide in the rat heart: effect of guanethidine and capsaicin

Vasoactive intestinal polypeptide (VIP) is believed to coexist with acetylcholine in postganglionic parasympathetic neurones. However, the presence of VIP in extrinsic nerves and/or other types of intrinsic cardiac neurones has not been excluded. The aim of our study was to examine the distribution and origin of VIP-ergic innervation in the rat heart atria using immunocytochemistry and radioimmunoassay (RIA) combined with two types of denervation: sympathectomy, which was produced by guanethidine treatment and sensory denervation achieved by capsaicin administration. In whole-mount preparations of the intact atria, VIP-immunoreactive (IR) nerve fibres and ganglionic cells were found, the latter being much more numerous in the left atria (LA) than in the right ones. Some of VIP-IR nerve fibres forming bundles appeared to be extrinsic in origin. VIP-IR concentrations determined by RIA in the intact rats were significantly higher in the LA than in the right ones (p < 0.01). However, no changes in VIP-IR levels were found in either atrium after both guanethidine and capsaicin treatment protocols, thus indicating that VIP-immunoreactivity is not associated with either sympathetic or sensory innervation. In conclusion, the ganglionated plexus of the rat atria may comprise at least 3 different neuronal populations expressing VIP-positivity: 1. extrinsic preganglionic parasympathetic fibres, 2. intrinsic postganglionic parasympathetic neurones and 3. intrinsic local circuit neurones that do not express a cholinergic phenotype.

Vasoactive intestinal polypeptide-containing elements in the olfactory bulb of the hedgehog ( Erinaceus europaeus)

The distribution of vasoactive intestinal polypeptide (VIP)-immunopositive elements was analyzed in the olfactory bulb (OB) of the Western European hedgehog ( Erinaceus europaeus) under light and electron microscopy. The immunoreactivity appeared in an abundant population of periglomerular cells of the glomerular layer, in interneurons of the external plexiform layer, and in a restricted group of deep short-axon cells of the internal plexiform layer, the granule cell layer and the white matter. In the glomerular layer, VIP-containing periglomerular cells constituted a population of non-GABAergic neurons and did not receive synapses from olfactory axons. In the EPL, VIP-immunoreactivity appeared in a morphologically heterogeneous population of GABAergic interneurons, most of them identified as satellite cells and Van Gehuchten cells. These interneurons exerted an abundant and selective innervation of the somata, primary and secondary dendrites of the principal mitral and tufted cells, but did not contact granule cells. Perisomatic innervation of the principal cells followed two different patterns. The first included ‘normal’ basket-like arrangements of VIP-containing varicosities surrounding the somata of mitral and tufted cells. In the second, a set of satellite cells gave rise to short dendritic shafts that embraced the somata of principal cells in an ‘exuberant’ basket-like arrangement. These two morphological patterns of perisomatic innervation of principal cells were correlated with a neurochemical specificity of the target. In this sense, the ‘exuberant’ basket-like structures were always found surrounding a subpopulation of principal cells that did not contain the calcium-binding protein parvalbumin (PV). By contrast, they were never found surrounding the subpopulation of PV-containing principal cells, which only showed ‘normal’ basket-like structures. This study provides new data on the connectivity and neurochemical features of the hedgehog olfactory bulb and suggests that the olfactory circuits in this species are more complex than those described in other mammals.

Simultaneous detection of receptor mRNA and ligand protein in human skin tissues.

In situ hybridization techniques allow a cell-type-specific messenger RNA (mRNA) analysis in complex tissues such as human skin. To evaluate both the expression of mRNA and protein within the same tissue section, we developed a protocol of combined non-radioactive in situ hybridization and immunohistochemistry for use in dermatohistopathology. To validate the technique, we assessed the distribution of vasoactive intestinal polypeptide (VIP) protein and its receptor, VPAC2 mRNA, in human skin samples. Simultaneous detection of VPAC2 mRNA and VIP immunoreactivity led to abundant staining for both signals in a variety of cell types. There was marked staining for VPAC2 mRNA in epidermal cells, with most pronounced hybridization signals found in keratinocytes of the basal layer and in glandular cells surrounded by VIP-immunoreactive nerve fibers. Hair follicle cells next to VIP-positive fibers also exhibited hybridization signals. Specific staining was also detected in endothelial and mononuclear cells. The findings of simultaneous in situ hybridization and immunohistochemistry were identical to results obtained by the single application of both methods. The combination of in situ hybridization and immunohistochemistry appears to be a promising technique to assess the expression of both protein and mRNA in skin samples and may be used for various purposes in experimental and clinical dermatopathology.

Expression of vasoactive intestinal polypeptide and calcitonin gene-related peptide in human stellate ganglia after acute myocardial infarction

Using the method of indirect immunofluorescence the distribution of vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) was investigated in autopsy specimens of human stellate ganglia following acute myocardial infarction (AMI). The dramatic increase of both VIP- and CGRP-immunoreactivities in principal ganglionic neurons as well as of calcitonin gene-related peptide in perineuronal nets was revealed. It was concluded that hypoxia and myocardial ischaemia following AMI are the main inducing factors for activation of both vasoactive regulatory neuropeptide synthesis. The upregulation of VIP and CGRP expression in sympathetic ganglionic neurons may provide regulatory and trophic support to the ischaemic heart.

Distribution of vasoactive intestinal polypeptide-, calcitonin gene-related peptide-, somatostatin- and neurofilament-immunoreactivities in sympathetic ganglia of human fetuses and premature neonates

The distribution patterns of vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), somatostatin (SOM) and neurofilament (NF) immunoreactivities (IR) were studied in the stellate ganglia of human fetuses and neonates at 24-26 weeks gestation. Sizeable populations with some quantitative variations of VIP-, CGRP- and SOM immunoreactive nerve cells were detected in all ganglia studied. In marked contrast, neurofilament expression was down-regulated. The upregulation of VIP, CGRP and SOM expression suggested their inductor effect on growth and differentiation neurons as well as on the development of their neurotransmitter properties. The main neuropeptides-inducing factor of sympathetic ganglia in human prenatal ontogenesis may be considered as a relative hypoxia.

Distribution of vasoactive intestinal polypeptide, neuropeptide-Y and substance P and their effects on insulin secretion from the in vitro pancreas of normal and diabetic rats☆

This study examined the pattern of distribution of vasoactive intestinal polypeptide (VIP), neuropeptide-Y (NPY) and substance P (SP) in the pancreas of diabetic rat to determine whether there are changes in the number and pattern of distribution of these neuropeptides after the onset of diabetes. Moreover, the effect of VIP, NPY and SP on insulin secretion from the pancreas of normal and diabetic rats was also examined. Diabetes mellitus (DM) was induced by a single dose of streptozotocin (STZ) given intraperitoneally (i.p.) (60 mg kg body weight −1). Four weeks after the induction of DM, diabetic ( n = 6) and normal ( n = 6) rats were anesthetized with chloral hydrate and their pancreases removed and processed for immunohistochemistry and insulin secretion. The number of insulin-positive cells in the islets of Langerhans was reduced while that of VIP and NPY increased significantly after the onset of diabetes. The pattern of distribution of VIP, NPY and SP in the nerves innervating the pancreas was similar in both normal and diabetic rats. VIP-evoked large and significant ( P < 0.02) increases in insulin secretion from the pancreas of normal and diabetic rats. NPY also induced a marked ( P < 0.005) increase in insulin release from pancreatic tissue fragments of normal rat. Stimulation of pancreatic tissue fragments of diabetic rat with NPY resulted in a slight but not significant increase in insulin release. SP induced a large and significant ( P < 0.005) increase in insulin secretion from the pancreas of normal rat but inhibited insulin secretion significantly ( P < 0.03) from isolated pancreas of diabetic rat. In summary, VIP and NPY can stimulate insulin secretion from the pancreas after the onset of diabetes. The stimulatory effect of SP on insulin secretion is reversed to inhibitory in diabetic rats.

Distribution of vasoactive intestinal polypeptide and its effect on glucagon secretion from normal and diabetic pancreatic tissue fragments in rat.

Distribution of vasoactive intestinal polypeptide and its effect on glucagon secretion from normal and diabetic pancreatic tissue fragments in rat.

Developmental changes in vasoactive intestinal polypeptide immunoreactivity in the human paravertebral ganglia

Vasoactive intestinal polypeptide (VIP) belongs to the glucagon-secretin family of polypeptides and possesses numerous functions. Its existence in the mammalian central and peripheral nervous system has been widely documented. However, there are no reports on the developmental aspects of VIP-like immunoreactivity (VIP-IR) in the human postganglionic sympathetic neurons. In this study the availability and distribution of vasoactive intestinal polypeptide has been localized in human stellate ganglia neurons and nerve fibers from neonates, children and adults using the immunohistochemical method. In neonatal ganglia VIP-immunoreactive postganglionic neurons were revealed in a marked population compared to others age-groups. These nerve cells are both small and large in size and are distributed in small clusters or singly in the area of ganglia sections. In children, VIP-IR in ganglionic neurons decreases. In adult stellate ganglia, VIP-immunoreactive postganglionic neurons rarely occur. In ganglia of an individual human only varicosities of VIP-positive nerve fibers were observed. These results provide the age-dependent reduction of VIP-like immunoreactivity in human stellate ganglia neurons and suggest the different role of this peptide in the function of sympathetic ganglia neurons with age.

Distribution of VIP receptors in the human submandibular gland: an immunohistochemical study.

Distribution of vasoactive intestinal polypeptide (VIP)-immunoreactive nerve fibers and VIP-receptor (VIP-R)-immunoreactive sites in the human submandibular gland were examined by the peroxidase-antiperoxidase method using the specimens taken from patients that had not received radiotherapy. VIP-immunoreactive fibers were found around both serous and mucous acini, the duct system, and those around the mucous acini were more numerous than those around the serous acini. VIP-R immunoreactivity was restricted to the mucous acini and the intercalated duct segment. The serous acini, striated duct, and excretory ducts lacked VIP-R immunoreactivity. These findings suggest that the mucous acinar cells contain VIP-R, and that VIP-R-mediated VIP action is involved in regulating synthesis of viscous saliva and its release.

Modular distribution of vasoactive intestinal polypeptide in the rat barrel cortex: changes induced by neonatal removal of vibrissae

The distribution of vasoactive intestinal polypeptide-immunoreactive neuronal structures in the barrel cortex (posteromedial barrel subfield) of adult rats was analysed after unilateral removal of the vibrissal follicles of row C in neonatal rats. The hypothesis was tested whether the distribution of vasoactive intestinal polypeptide-immunoreactive structures depends on the normal anatomical organization of the specific sensory input. After three months survival the distribution of the vasoactive intestinal polypeptide-immunoreactive structures was morphometrically evaluated. This approach revealed alterations in the contralateral posteromedial barrel subfield, where the disappearance of barrel row C and a substantial increase in size mainly of barrel row D, but also of other rows could be detected. Increase in row D included both barrels and the interspace (septal segments between barrels in one row). As vasoactive intestinal polypeptide immunoreactivity of the barrel field was found previously to be localized in synaptic boutons involved in symmetric synapses, our present findings suggest that (i) the interspace is enriched in inhibitory vasoactive intestinal polypeptide-immunoreactive synapses as opposed to the excitatory thalamocortical input reaching the barrel hollow, (ii) the spatial distribution of the vasoactive intestinal polypeptide system in the barrel cortex is closely associated with the neuronal organization of the sensory input and reacts with a considerable plasticity to lesion-induced changes of the input, and (iii) the compensatory barrel hypertrophy in a row neighbouring the deafferented row involves an increasing number of vasoactive intestinal polypeptide-immunoreactive synapses per barrel.

기니픽 상기도의 Vasoactive Intestinal Polypeptide 함유 신경의 분포

기니픽 상기도의 Vasoactive Intestinal Polypeptide 함유 신경의 분포

Axon terminals containing PACAP- and VIP-immunoreactivity form synapses with CRF-immunoreactive neurons in the dorsolateral division of the bed nucleus of the stria terminalis in the rat

The bed nucleus of the stria terminalis (BST) is a highly heterogeneous forebrain structure, within which the median and lateral BST play distinct functional roles. The medial BST (BSTM) is thought to be related to sexual behavior, while the lateral BST (BSTL) may have a stress-related function. In the human brain, the BST shows marked sexual dimorphism in the distribution of vasoactive intestinal polypeptide (VIP) immunoreactive fibers and also contains a very high concentration of pituitary adenylate cyclase activating polypeptide (PACAP) immunoreactivity (ir). Using immunohistochemistry (IHC) to examine the rat brain, the present study found that both VIP and PACAP containing afferent fibers are abundant in the BSTLd (dorsolateral division of BST), but not in the BSTM. IHC did not reveal any apparent difference between the sexes in the size of distribution of either immunoreactivity. Double staining IHC showed that axonal terminals of both VIP and PACAP neurons were in close proximity to dendrites or perikarya of corticotropin releasing factor (CRF) neurons. At the electron microscopic level IHC revealed the presence of axodendritic or axosomatic synapses between VIP-ir and PACAP-ir axon terminals and CRF-ir neurons. Although the origin of PACAP-ir fibers in the BSTLd remains to be determined, these morphological findings suggest that PACAP and VIP regulate the activity of CRF neurons in the BSTLd as neurotransmitters or neuromodulators.

Distribution of vasoactive intestinal polypeptide immunoreactive nerve fiber in the rat nasal mucosa

The distribution of vasoactive intestinal polypeptide (VIP)-immimoreactive nerve fiber of the respiratory nasal mucosa of the rat was examined by use of immunohistochemistory with light, laser confocal scanning and electron microscopy. On light microscopy, it was observed that VIP immunoreactive nerve fibers distributed under and within the epithelium in addition to around the blood vessels and glands. The laser confocal scanning microscope revealed the network of VIP-immunoreactive nerve fibers at glands, but it was denser around glands than within glands. The VIP-immunoreactive nerve fibers formed fine varicosities and was distributed below the middle portion of the epithelium. Some fibers were observed as if they were surrounding goblet cells. Electron microscopy showed that the VIP-immunoreactive nerve fibers within the epithelium were terminated as free nerve endings. Some of them were in close contact with goblet cells.

Intrinsic innervation of the stomach of the fetal pig: an immunohistochemical study of VIP-immunoreactive nerve fibres and cell bodies.

Using an immunohistochemical technique, the presence and distribution of vasoactive intestinal polypeptide (VIP) was investigated in cryostat sections, both tangential and transverse, of the fetal pig's stomach. In all fetuses and in all gastric segments investigated, VIP-like immunoreactive (IR) nerve-cell bodies were seen in all intramural ganglia, and VIP-IR nerve fibres were found in all layers of the gastric wall except the tunica serosa. Consequently, VIP-IR nerve fibres were found to form a periglandular network, to accompany arterioles, to interconnect the intramural ganglia, to encircle both VIP-IR-negative and -positive neurons, and were found in all muscle layers. Despite the fact that VIP-IR seems to be restricted to the intramural nervous elements, some non-specific-reacting VIP-IR glandular cells were noticed in the basal parts of the fundic, antral and pyloric gastric glands. The distribution pattern of VIP in the fetal pig resembles that of the adult pig. This suggests a possible functional role for VIP during fetal life and/or puts forward the suggestion that the stomach of a fetal pig from the second half of the gestation period is prepared, from then on, for postnatal function. High similarities with regard to the general distribution pattern of VIP in the stomach have also been noted between the fetal pig and humans, proving once more that the fetal pig can serve as a good animal model in several research areas. Finally, the morphological data provided here may, combined with the physiological significance of VIP, contribute to a better insight into the physiopathology of economically important gastro-intestinal disorders in the pig, such as gastric ulceration.

Distribution and origin of nitric oxide synthase-immunoreactive nerve fibers in the rat epididymis

Distribution of neuronal nitric oxide synthase-immunoreactive (nNOS-IR) nerve fibers and somata in the rat epididymis and major pelvic ganglia was studied by immunohistochemical methods. In the epididymis, the supply of nNOS-IR fibers was highest in the cauda and became progressively fewer toward the caput. In the cauda and corpus, nNOS-IR fibers were distributed throughout the subepithelial tissues and around the epithelium. The pattern of distribution of vasoactive intestinal polypeptide (VIP)- and tyrosine hydroxylase (TH)-immunoreactive fibers in the epididymis was similar but the latter was generally more numerous in a given region as compared to that of nNOS-IR fibers. A population of neurons in the major pelvic ganglia were nNOS-, TH- or VIP-IR. Double-labeling studies revealed that few neurons in the major pelvic ganglia contained both nNOS-IR and TH-IR. Whereas nNOS-IR and VIP-IR appeared to co-localize in the same population of pelvic ganglion cells. Similarly, nNOS-IR fibers in the epididymis were mostly VIP-positive and TH-negative. Unilateral injection of the fluorescent tracer Fluorogold into the junction between the vas deferens and the cauda labeled a population of neurons in the right and left major pelvic ganglia, some of which were also nNOS-IR. A small number of dorsal root ganglion cells contained Fluorogold and very few expressed NOS-IR. It may be concluded that nNOS-IR nerve fibers in the rat epididymis arise mainly from neurons in the major pelvic ganglia the major of which express VIP-IR but not TH-IR. The extensive supply of nNOS-immunoreactive fibers around the epithelium and throughout the subepithelial tissues suggests that NO may be closely associated with smooth muscle contraction.

The occurrence of cutaneous nerve endings and neuropeptides in vitiligo vulgaris: a case-control study.

Pioneering studies both in humans and animals have demonstrated an association between the peripheral nervous system and epidermal melanocyte destruction. The presence of certain neuropeptides and neuronal structural markers in peripheral nerve fibres was investigated in involved and uninvolved vitiligo skin and compared with normal healthy skin. A group of 18 vitiligo vulgaris patients and matched healthy volunteers participated in the investigation. The indirect immunofluorescence technique was employed. There was a tendency for a reduction in the number and intensity of low affinity (p75) nerve growth factor receptor immunoreactive (NGFr-IR) basal keratinocytes in involved vitiliginous skin (P < 0.06) compared with control skin, while the number of NGFr-IR nerve fibres was significantly increased (P < 0.01). The number of calcitonin gene-related peptide (CGRP)-IR nerve fibres in the epidermis and papillary dermis was dramatically increased in involved skin as compared with control skin (P < 0.01) and with uninvolved skin (P < 0.05). No clear difference could be found in the distribution of vasoactive intestinal polypeptide (VIP)- and neuropeptide tyrosine (NPY)-IR nerve fibres. A different structural appearance of the peripheral nervous system as well as a changed balance of neuropeptides in vitiliginous skin point to a critical role of the nervous system in the pathogenesis of vitiligo.

Investigative Urology: Modulation of Vasoactive Intestinal Polypeptide (VIP)-Mediated Relaxation by Nitric Oxide and Prostanoids in the Rabbit Corpus Cavernosum

The polypeptide VIP has been proposed as an inhibitory nonadrenergic, noncholinergic (NANC) neurotransmitter involved in the relaxation of cavernosal smooth muscle during erection. However, the specific mechanism(s) by which VIP exerts its effect is unknown. To determine whether VIP is involved in NANC-mediated cavernosal relaxation, strips of corpus cavernosum from New Zealand White rabbits were hung in tissue baths; atropine and guanethidine were added to block cholinergic and adrenergic neurotransmission, respectively. The tissue was then submaximally precontracted with norepinephrine (NE) and relaxed by electrical field stimulation (EFS; 10 V square waves, 0.5 msec. duration, 10 second trains at 5, 15 and 40 Hz) before and after preincubation with the VIP antagonist, VIP 10-28. To evaluate the role of nitric oxide (NO) and prostaglandins on the relaxant effect of VIP in the corpus cavernosum, the strips were contracted with NE and subsequently relaxed with cumulative doses of VIP (10(-10) to 10(-6) M.). After VIP dose-response curves were obtained, the strips were preincubated with N omega-nitro-L-arginine (NOARG, an inhibitor of nitric oxide synthase, 10(-4) M.) and the VIP dose-response curve was repeated. Indomethacin (10(-5) M.) was added to one-half of the NOARG treated strips to inhibit prostaglandin synthesis. VIP 10-28 inhibited EFS-induced relaxation (p < 0.05) and produced dose-dependent relaxation, which was inhibited by NOARG (p < 0.05). In contrast, the VIP-induced relaxation was more pronounced in the presence of indomethacin (p < 0.05). Moreover, indomethacin substantially reversed the NOARG inhibition of VIP relaxation (p < 0.05). These results suggest that VIP is a mediator of NANC cavernosal relaxation and that NO synthesis is involved in VIP-induced NANC relaxation in the corpus cavernosum. In addition, the presence of vasoconstrictive prostanoids modulates this VIP-mediated NANC relaxation. Therefore, VIP appears to contribute to NANC neurally mediated cavernosal relaxation, and its mechanisms of relaxation are dependent on prostanoid and involve the generation of NO.