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Biomedical subjects

S I Said

Publications and source records attributed to S I Said.

At least 55 records · Page 3Linked to original sources
PubMed1993

Colocalization of vasoactive intestinal peptide and nitric oxide synthase in neurons of the ferret trachea.

Neurally-mediated relaxation of smooth muscle in human, guinea-pig, cat, and pig airways is largely attributed to a nonadrenergic, noncholinergic mechanism. While the specific transmitter(s) of this relaxant system have not been conclusively identified, vasoactive intestinal peptide and nitric oxide have emerged as likely mediators in airway smooth muscle. Both vasoactive intestinal peptide and nitric oxide relax guinea-pig, pig and human smooth muscle. Vasoactive intestinal peptide is present in nerve fibers associated with airway smooth muscle in humans and several animal species. In guinea-pigs, vasoactive intestinal peptide is released during electrical field stimulation of airway strips and the release correlates with the nonadrenergic relaxation. This relaxation is markedly reduced after incubation of tracheal tissue with a specific VIP antibody and by immunization to vasoactive intestinal peptide. Similarly, nonadrenergic relaxations induced by electrical field stimulation are reduced in human, pig, guinea-pig and bovine airways by nitric oxide synthesis inhibitors. Vasoactive intestinal peptide is present in nerve cell bodies of airway ganglia, suggesting that these nerves in airway smooth muscle originate from intrinsic neurons. It is stored in dense-core vesicles of nerve terminals near airway smooth muscle, suggesting that preformed vasoactive intestinal peptide is released by fusion of the vesicles with the cell membrane of the nerve terminal. Nitric oxide is probably generated by a novel mechanism involving de novo synthesis at the nerve terminal during neural activation by the action of the enzyme nitric oxide synthase.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1993

Vasoactive intestinal peptide enhances lung preservation.

The outcome of lung transplantation is often dependent on the quality of the donor lungs. To explore a way to improve lung preservation, vasoactive intestinal peptide (VIP) was added to pneumoplegic solutions. The 4 solutions tested were Krebs solution, Krebs solution with VIP, University of Wisconsin solution, and the University of Wisconsin solution with VIP. The lungs of 8 male Sprague-Dawley rats were flushed and stored in these solutions for 24 hr. At regular intervals, tissue was sampled and examined by light, scanning, and transmission electron microscopy. Casts of the vasculature were made after 4 hr and viewed by a scanning electron microscope. Lungs appeared well preserved by light microscopy at all intervals. Although inflammatory cells around arteries, arterial constriction, bronchiolar epithelial detachment, peribronchiolar edema, and alveolar size inhomogeneity were greater with time, there was no significant difference among the 4 groups by light microscopy. Scanning microscopy of tissue at 24 hr confirmed the information found on light microscopy but did not allow separation of the groups. The vascular casts showed that edema around large vessels was less in the lungs treated with VIP (P < 0.01). Transmission electron microscopy showed that lungs stored in the solutions with VIP had significantly more normal-shaped mitochondria, less mitochondrial edema, less distortion of mitochondrial cristae, thinner basal lamina, and less aggregation of nuclear chromatin at most intervals sampled after 4 hr. We conclude that VIP added to certain pneumoplegic solutions improves the ultrastructure of rat lung stored in the cold for up to 24 hr. VIP may be an important additive to pneumoplegic solutions to improve preservation of lung before transplantation.

Adenosine↗
PubMed1993

Paraquat-induced lung injury: prevention by vasoactive intestinal peptide and related peptide helodermin.

We earlier showed that the neuropeptide vasoactive intestinal peptide (VIP) reduces or prevents acute injury produced in rat lungs by xanthine and xanthine oxidase. We have now examined whether VIP can protect against lung injury induced by paraquat, a prooxidant pesticide. Isolated guinea pig lungs were perfused for 60 min with Krebs-4% albumin and mechanically ventilated with 95% O2-5% CO2. Infusion of paraquat (100 mg/kg) into the pulmonary artery (n = 9 observations) increased peak airway pressure from 10.1 +/- 0.6 to 54.7 +/- 6.5 cmH2O, perfusion pressure from 8.0 +/- 0.5 to 14.9 +/- 3.0 cmH2O, wet-to-dry lung weight ratio to 7.17 +/- 0.37, and bronchoalveolar lavage protein content to 2.70 +/- 0.83 mg/ml (P < 0.01). Pretreatment with 1-3 micrograms.kg-1 x min-1 VIP markedly attenuated or prevented all abnormalities. Of the related peptides tested, helodermin was as effective as VIP, but secretin and glucagon were ineffective. The results demonstrate that VIP and helodermin protect perfused guinea pig lungs against paraquat-induced injury and support the view that VIP has antioxidant activity.

Animals↗
PubMed1992

Vasoactive intestinal polypeptide (VIP) inhibits rat alveolar macrophage phagocytosis and chemotaxis in vitro.

Vasoactive intestinal polypeptide (VIP) has been shown to inhibit lymphocyte function and is believed to modulate the immune response. We explored the possible immunomodulatory effects of VIP on alveolar macrophage (AM) function by examining its influence on AM phagocytosis and chemotaxis. Rat AMs were collected by bronchoalveolar lavage and incubated for 90 min with polystyrene beads in the presence or absence of VIP in concentrations from 10(-11) M to 10(-5) M. VIP significantly (P less than 0.0001) inhibited AM phagocytosis of polystyrene beads at concentrations of 10(-11) to 10(-6) M, with a maximal inhibition of 35% at 10(-6) M (but no inhibition at 10(-5) M). AMs were also incubated for 90 min in a chemotaxis chamber with endotoxin-activated rat serum (EARS) as a chemoattractant, with or without VIP in concentrations from 10(-9) to 10(-6) M. VIP significantly (P less than 0.0001) inhibited AM chemotaxis by at least 30% at concentrations of 10(-9) to 10(-6) M, with a maximal inhibition of 46% at 10(-7) M. These results indicate that VIP, in concentrations from 10(-11) to 10(-6) M, inhibits rat AM function as assessed by phagocytosis of polystyrene beads and chemotaxis to EARS. The inhibition of alveolar macrophage function is another mechanism by which VIP may modulate the immune response in the lung.

Animals↗
PubMed1992

Contractile activity of vasotocin, oxytocin, and vasopressin on mammalian prostate.

The neurohypophyseal peptides arginine vasotocin, oxytocin and arginine vasopressin contracted guinea pig, rat, canine and human prostates with potencies and efficacies that were comparable to those of noradrenaline and methacholine. All three neuropeptides raised prostatic tone and elicited contractions at 10(-9) or 10(-8) M, with an order of efficacy: arginine vasotocin greater than oxytocin greater than arginine vasopressin. The findings suggest a physiological role for these peptides in prostatic smooth muscle contraction and possibly also in other aspects of male reproductive function.

Animals↗
PubMed1992

Paraquat-induced lung injury: prevention by N-tert-butyl-alpha-phenylnitrone, a free-radical spin-trapping agent.

The herbicide paraquat causes lung injury that is believed to be oxygen-radical mediated. To further characterize this injury and explore new methods of preventing it, we used the spin-trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) to identify the paraquat radical in lung tissue and to reduce the injury resulting from the subsequent generation of reactive oxygen species. The formation of a paraquat free radical by guinea pig lung was detected under anaerobic conditions by electron paramagnetic resonance spectrometry. Infused (25, 50, or 100 mg/kg) into guinea pig lungs (perfused at constant flow with Krebs solution containing 4% bovine serum albumin and ventilated with 95% O2-5% CO2), paraquat produced dose-dependent increases in peak airway pressure (Paw), mean pulmonary arterial perfusion pressure (Ppa), and wet-to-dry (W/D) lung weight ratio. At 100 mg/kg, paraquat increased Paw by 589.6 +/- 59.8% (mean +/- SE, n = 8) and W/D ratio from 5.33 +/- 0.07 to 6.29 +/- 0.11 (P less than 0.001). Pulmonary vascular leak index increased from 0.40 +/- 0.09 to 1.96 +/- 0.45 (P less than 0.02), without changes in pulmonary microvascular pressure. Perfusate concentrations of thromboxane B2 and 6-ketoprostaglandin F1 alpha increased, but indomethacin did not reduce the injury. PBN (2.3 mM) markedly attenuated all evidence of lung injury, which was also reduced by catalase, mannitol, ethanol, and vitamin E.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Co-occurrence of immunoreactive calcitonin and calcitonin gene-related peptide in neuroendocrine cells of rat lungs.

Neuroendocrine cells of the lung, occurring singly or in clusters known as neuroepithelial bodies, contain a variety of biologically active compounds, including several neuropeptides. We have investigated the localization of calcitonin and calcitonin gene-related peptide (CGRP) within single and grouped neuroendocrine cells in the respiratory epithelium of rats by an immunohistochemical double-staining technique which uses specific antisera raised in heterogeneous animal species. Calcitonin- and CGRP-immunoreactivities were nearly totally co-localized in both single neuroendocrine cells and neuroepithelial bodies. CGRP-immunoreactivity was also present in neurons in the jugular, nodose and dorsal root ganglia. The calcitonin-immunoreactivity in neuroendocrine cells, as in thyroid parafollicular (C) cells, was abolished by preincubation of the anti-calcitonin serum with synthetic calcitonin. The CGRP-immunoreactivity in neuroendocrine cells and in the neuronal cells was abolished by preincubation of anti-CGRP serum with synthetic CGRP. Thus, while the calcitonin gene is expressed exclusively or predominantly as either calcitonin or CGRP in all other tissues except thyroid C-cells, our results strongly suggest that both peptides are expressed in the rat bronchopulmonary neuroendocrine cells.

APUD Cells↗
PubMed1991

Vasoactive intestinal peptide and nerve regeneration.

The role of vasoactive intestinal peptide (V.I.P.) in nerve regeneration was investigated by assessing the changes in immunoreactive V.I.P. levels in rat sciatic nerves following injury and repair. 60 rats were divided into three surgical groups and one control group: In group I (primary repair), sciatic nerves were divided and immediately repaired; in group II (secondary repair), sciatic nerves were divided and repaired two weeks later; in group III (no repair), sciatic nerves were divided and not repaired; and in group IV (controls), sciatic nerves were exposed but not divided. Animals were sacrificed at three days and at weekly intervals. Their sciatic nerves were extracted and assayed for V.I.P. concentrations by a specific radioimmunoassay. The mean V.I.P. concentration varied between 22 and 46 pg./mg. protein in the control nerves and between 60 and 529 pg./mg. protein in all other groups. In the three surgical groups the levels were significantly higher in proximal than in distal stumps. Following nerve injury, there was an increase in V.I.P. concentration in the injured and repaired areas. This increase was greater in injured non-repaired areas and was highest in the first 48 hours, but continued during regeneration. The accumulation of V.I.P. in divided nerves occurred in response to nerve injury.

Animals↗
PubMed1991

Pulmonary calcitonin gene-related peptide immunoreactivity: nerve-endocrine cell interrelationships.

Respiratory epithelium has been reported to be supplied with sensory nerves and to contain irritant and other receptors. In this immunohistochemical study, we examined the incidence, morphology, and distribution of calcitonin gene-related peptide (CGRP) immunoreactivity in epithelial cells the rat respiratory tract, using peroxidase anti-peroxidase (PAP) techniques. CGRP immunoreactivity was localized in capsaicin-sensitive nerve fibers and in capsaicin-nonsensitive endocrine cells occurring singly or in groups. These CGRP-immunoreactive structures reached close to or actually touched the airway lumen, were widely and abundantly present in the respiratory epithelium, and were arranged in distinct and characteristic patterns. CGRP-immunoreactive nerves innervated not only grouped cells but also single cells, and the innervation of these cells differed depending on whether they were in extrapulmonary or intrapulmonary epithelium. The specificity of the immunoreactivity was confirmed by absorption tests that excluded cross-reactivity with other peptides. The results suggest that epithelial nerve fibers and endocrine-like cells exhibiting CGRP immunoreactivity form a morphologic, and probably also a functional, complex throughout the respiratory epithelium. CGRP innervation may be related to receptor functions of respiratory epithelium.

Animals↗
PubMed1990

Direct evidence for the involvement of vasoactive intestinal polypeptide in the motor response of the human isolated ileum to capsaicin.

Capsaicin (1 microM) produced complex motor responses in longitudinal and circular muscle strips from the human isolated small intestine (jejunum and ileum). In the longitudinal muscle, inhibition of the nerve-mediated contractions (electrical field stimulation) was the dominant response, while capsaicin had a weak and inconsistent effect on tone and spontaneous activity. In contrast, relaxation and decreased spontaneous activity were the responses of the circular muscle to capsaicin. These effects of capsaicin were not reproduced by a second application of capsaicin, indicating desensitization, a feature of the specific action of this drug on sensory nerves. All the effects of capsaicin in the longitudinal and circular muscle were closely mimicked by exogenous vasoactive intestinal polypeptide (VIP). Further, the inhibitory motor effect of capsaicin in both muscle layers was blocked by an anti VIP serum. In the longitudinal muscle, VIP, like capsaicin, inhibited the electrically evoked nerve-mediated contractions but not the tetrodotoxin-resistant myogenic contractions, suggesting a prejunctional site of action. The inhibitory effect of both capsaicin and VIP in the circular muscle was tetrodotoxin-resistant suggesting direct inhibition of muscle cells. Capsaicin (1 microM) evoked a tetrodotoxin-resistant release of VIP-like immunoreactivity from the human small intestine. On high pressure liquid chromatography, a major peak of the immunoreactive material released by capsaicin co-eluted with authentic VIP and a minor, unidentified peak eluted shortly afterward. We conclude that authentic VIP is involved in the local motor response to capsaicin in the human small intestine. These findings raise the possibility that VIP might be present in sensory nerves of the human gut from which it is released by capsaicin.

Aged↗
PubMed1990

[Met]enkephalin-Arg6-Gly7-Leu8-immunoreactive nerves in guinea-pig and rat lungs: distribution, origin, and co-existence with vasoactive intestinal polypeptide immunoreactivity.

[Met]Enkephalin-Arg6-Gly7-Leu8 is an endogenous opioid peptide, first isolated from the bovine adrenal medulla. Because this octapeptide is specifically contained in the amino acid sequence of preproenkephalin A but not in other opioid precursors like preproopiomelanocortin or preproenkephalin B, [Met]enkephalin-Arg6-Gly7-Leu8 has been regarded as a specific marker for preproenkephalin A and its derivatives. In this study, we examined the occurrence and origin of [Met]enkephalin-Arg6-Gly7-Leu8-immunoreactive nerves in the guinea-pig and rat lung by immunohistochemical techniques, using a specific antiserum against this peptide. In addition, we investigated the possible co-existence of [Met]enkephalin-Arg6-Gly7-Leu8 and vasoactive intestinal peptide immunoreactivity in neuronal elements of the respiratory tract. In both species, [Met]enkephalin-Arg6-Gly7-Leu8 immunoreactivity was localized in nerve fibers chiefly distributed to the trachea and major bronchi, where they were prevalent in smooth muscle bundles, in the lamina propria, around airway glands, and in the walls of pulmonary vessels, but were absent in airway epithelium. Slight differences in the distribution pattern of immunoreactive nerve fibers were noted between the two species: immunoreactive nerve fibers in the smooth muscle bundles were much more abundant in guinea-pigs than in rats, while those in the mucous glands were richer in rats than in guinea-pigs. Neither chemical sympathectomy by 6-hydroxydopamine, nor chemical sensory denervation by capsaicin, changed the density or distribution of [Met]enkephalin-Arg6-Gly7-Leu8-immunoreactive nerve fibers in the airway, suggesting an intrinsic source for these nerve fibers. Colchicine injection into the tracheal wall, to promote the accumulation of neuropeptides in nerve cell bodies, led to the visualization of [Met]enkephalin-Arg6-Gly7-Leu8 immunoreactivity in some neuronal cell bodies within airway ganglia. Immunostaining for [Met]enkephalin-Arg6-Gly7-Leu8 and for vasoactive intestinal polypeptide on serial adjacent sections of airway ganglia obtained from colchicine-treated tracheae, demonstrated the co-existence of these immunoreactivities in a population of nerve cell bodies in these ganglia. The immunohistochemical localization of immunoreactive [Met]enkephalin-Arg6-Gly7-Leu8 in nerve elements in guinea-pig and rat lungs provides a morphological basis for the possibility that preproenkephalin A-related opioid peptides may have a neuromodulatory role in mammalian airways and pulmonary vessels.

Animals↗
PubMed1990

A clinical trial of intracavernous vasoactive intestinal peptide to induce penile erection.

A double-blind, placebo-controlled clinical trial of the intracavernous injection of vasoactive intestinal peptide was conducted and studied in 24 men with erectile dysfunction of diabetic, neurogenic and psychogenic etiology. The patients were randomized into 6 groups of 4 subjects each and received either placebo, or 200 or 400 pmol. vasoactive intestinal peptide at each of 3 consecutive weekly visits. An increase in penile length was associated significantly with treatment (F equals 5.10, p equals 0.01), dose-related, and independent of the time and sequence of treatment. An increase in penile diameter was associated significantly with treatment (F equals 8.14, p equals 0.001) and time (F equals 8.14, p equals 0.001), dose-related and independent of the sequence of treatment. Penile rigidity was associated significantly with time (F equals 5.44, p equals 0.008), associated nearly significantly with treatment (F equals 3.11, p equals 0.056) and independent of sequence of treatment. Despite some measurable treatment-related increase none of the patients achieved penile rigidity adequate for intromission.

Adult↗