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Biomedical subjects

S I Said

Publications and source records attributed to S I Said.

At least 19 recordsLinked to original sources
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↗
PubMed1990

Direct coronary vasodilation induced by intracoronary vasoactive intestinal peptide.

Vasoactive intestinal peptide (VIP) is a neurotransmitter that has been identified in epicardial coronary arteries. To evaluate the direct effect of VIP on coronary hemodynamics and blood flow, graded doses of VIP (0.01, 0.03, 0.10, and 0.30 micrograms/min) were infused into the left coronary artery of 7 patients at the time of diagnostic cardiac catheterization for chest pain syndromes. None of the patients had coronary stenoses greater than 50% during subsequent angiography. Coronary sinus VIP concentrations increased during each infusion (22 +/- 28 pg/ml at baseline to 109 +/- 22 pg/ml at 0.30 micrograms/min; p less than 0.05), but arterial VIP was elevated (39 +/- 29 pg/ml) only at the maximal dose of 0.30 micrograms/min. During all dosages of VIP, heart rate, right atrial and left ventricular end-diastolic pressure, and the heart rate x blood pressure product did not change. Moreover, neither mean aortic pressure nor left ventricular peak + dP/dt changed significantly at doses less than 0.30 micrograms/min; at 0.30 micrograms/min, mean aortic pressure decreased (97 +/- 15 to 90 +/- 15 mm Hg; p less than 0.05) and LV peak + dP/dt increased (1,621 +/- 230 to 1,801 +/- 226 mm Hg/s; p less than 0.05). Compared to baseline, the arterial-coronary sinus O2 content difference and myocardial O2 extraction diminished progressively at the 0.03, 0.10, and 0.30 micrograms/min doses of VIP (118 +/- 12 ml O2/L vs. 94 +/- 15, 70 +/- 9, and 61 +/- 26 ml O2/L, respectively, and 0.64 +/- 0.05 vs. 0.53 +/- 0.10, 0.38 +/- 0.06, and 0.34 +/- 0.15, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Vasoactive intestinal peptide prevents lung injury due to xanthine/xanthine oxidase.

Reactive oxygen species mediate injury and inflammation in many tissues. The addition of xanthine and xanthine oxidase to perfused rat lungs led to increases in peak airway pressure and perfusion pressure, pulmonary edema, and increased protein content in bronchoalveolar lavage fluid. Treatment with 1-10 micrograms.kg-1.min-1 of vasoactive intestinal peptide (VIP), a widely distributed neuropeptide, markedly reduced or totally prevented all signs of injury. Simultaneously, VIP also diminished or abolished the associated generation of arachidonate products. Similar protection was provided by catalase (100 micrograms/ml) but not by the VIP-related peptides secretin or glucagon. The pulmonary vasodilator papaverine (0.15 mg/ml) was also ineffective. Injured lungs that were not treated with VIP released large amounts of this peptide in the perfusate. The results indicate that VIP has potent protective activity against injury triggered by xanthine/xanthine oxidase and may be a physiological modulator of inflammatory tissue damage associated with toxic oxygen metabolites.

Animals↗
PubMed1990

EPR spectroscopic studies of detection of a carbon-centered free radical during acetylcholine-induced and endothelium-dependent relaxation of guinea pig pulmonary artery.

Vascular smooth muscle relaxation by several vasodilators, including acetylcholine (Ach) and ATP, depends on the presence of intact endothelium. Ach is thought to activate muscarinic receptors on endothelium to release an endothelium-derived relaxing factor (EDRF) which brings about relaxation of smooth muscle. In order to assess the role of free radicals in the endothelium-dependent relaxation of blood vessel, we have studied the effect of a spin-trapping agent, phenyl t-butyl nitrone (PBN), on Ach-, ATP-, and sodium nitroprusside-induced relaxation of guinea pig pulmonary artery. Arterial strips were mounted in a 5-ml organ bath containing Krebs solution equilibrated with 95% O2 and 5% CO2 at 37 degrees C. After increasing vascular tone by a synthetic prostaglandin endoperoxide analog (50 ng/ml), the strips relaxed dose-dependently in response to Ach (5 x 10(-8) M), ATP (1.5 x 10(-6) M) or sodium nitroprusside (6 x 10(-9) M). Removal of the endothelium abolished the relaxation by Ach or ATP, but did not affect the relaxation by sodium nitroprusside. PBN inhibited Ach-induced relaxation of pulmonary artery dose-dependently, but had no effect on relaxations by ATP or sodium nitroprusside. PBN did not block radioligand binding to muscarinic cholinergic membrane receptors on both chick embryonic heart and guinea pig pulmonary artery endothelial cells indicating that it does not block the muscarinic receptors. Spin trapping in combination with electron paramagnetic resonance (EPR) spectral analysis revealed a carbon-centered radical with hyperfine splitting constants of aN = 16.0 G and aH beta = 3.85G in the lipid extracts of pulmonary artery (0.2-0.4 g) incubated with PBN (14 mM) and Ach (3 x 10(-6) M) for 20 min. No signal was detected when endothelium was removed. Our data suggest that the endothelium-dependent relaxation of pulmonary artery by Ach is associated with the generation of a free-radical and can be prevented by a spin-trapping agent. ATP, however, relaxes the arterial smooth muscle by a different mechanism.

Acetylcholine↗