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Biomedical subjects

S I Said

Publications and source records attributed to S I Said.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1989

Characterization of autoantibodies to vasoactive intestinal peptide in asthma.

Vasoactive intestinal peptide (VIP) is a potent relaxant of the airway smooth muscle. In this study, VIP-binding autoantibodies were observed in the plasma of 18% asthma patients and 16% healthy subjects. Immunoprecipitation studies and chromatography on DEAE-cellulose and immobilized protein G indicated that the plasma VIP-binding activity was largely due to IgG antibodies. Saturation analysis of VIP binding by the plasmas suggested the presence of one or two classes of autoantibodies, distinguished by their apparent equilibrium affinity constants (Ka). The autoantibodies from asthma patients exhibited a larger VIP-binding affinity compared to those from healthy subjects (Ka 7.8 x 10(9) M-1 and 0.13 x 10(9) M-1, respectively; P less than 0.005). The antibodies were specific for VIP, judged by their poor reaction with peptides bearing partial sequence homology with VIP (peptide histidine isoleucine, growth hormone releasing factor and secretin). IgG prepared from the plasma of an antibody-positive asthma patient inhibited the saturable binding of 125I-VIP by receptors in guinea pig lung membranes (by 39-59%; P less than 0.001). These observations are consistent with a role for the VIP autoantibodies in the airway hyperresponsiveness of asthma.

Adult↗
PubMed1989

Coronary hemodynamic effects of intravenous vasoactive intestinal peptide in humans.

Vasoactive intestinal polypeptide (VIP), a probable neurotransmitter, is present in the hearts of experimental animals and is a coronary vasodilator in dogs. We evaluated the coronary hemodynamic effects of intravenously infused VIP in 11 men at two rates that modestly raised circulating VIP concentrations. The decreases in coronary and systemic vascular resistances during the second infusion, 33 and 31%, respectively, were slightly but insignificantly greater than the 24% decrease in pulmonary vascular resistance. Coronary sinus levels of 6-keto-prostaglandin F1 alpha were not elevated during the infusions, and cyclooxygenase inhibition did not significantly blunt coronary vasodilation. However, myocardial oxygen uptake rose significantly during both infusions. To test for a direct coronary vasodilator effect, we infused VIP into the left coronary artery of four other men at four levels. The maximum decline in coronary vascular resistance was 46% and was not associated with an increase in myocardial oxygen uptake. We conclude that 1) intravenous administration of low to intermediate doses of VIP in humans is associated with substantial coronary vasodilation, 2) the coronary bed appears to be at least as responsive as other vascular beds, 3) the coronary vasodilation is due to both direct and indirect effects, and 4) the coronary vasodilation does not appear to be mediated by prostaglandins.

Blood Pressure↗
PubMed1989

Immunohistochemical demonstration of enkephalin-containing nerve fibers in guinea pig and rat lungs.

Met-enkephalin (Met-Enk) and Leu-enkephalin (Leu-Enk), the opioid peptides originally isolated from the brain, are believed to act as inhibitory neuromodulators at various synaptic sites. In this immunohistochemical study, we have investigated the localization and distribution of Met- and Leu-Enk immunoreactivities in airways and pulmonary vessels of guinea pigs and rats. Immunoreactivities to both peptides were found in nerve fibers and nerve terminals distributed mainly to the trachea and major bronchi, and were especially prevalent in the smooth muscle layer, in the lamina propria, and around tracheal and bronchial glands, but not in the epithelium. Few immunoreactive nerve fibers were detected in smaller bronchi, bronchioles, and alveoli. Enkephalin-immunoreactive nerve fibers were also localized in the walls of pulmonary and bronchial vessels. Within airway microganglia, immunoreactivity was observed in a few nerve terminals, but not in ganglion cell bodies. Met- and Leu-Enk immunoreactive nerve fibers showed similar distribution patterns, though minor differences were noted between the two species: Enk-immunoreactive nerve fibers in the smooth muscle layer were more abundant in guinea pigs than in rats, whereas those in mucous glands were richer in rats than in guinea pigs. These results document the presence of Met- and Leu-Enk immunoreactivity in nerve fibers supplying guinea pig and rat airways and pulmonary vessels, and provide a morphologic basis for the view that enkephalins are likely neurotransmitters or neuromodulators in the lung.

Animals↗
PubMed1989

Bronchiectasis and progressive respiratory failure following smoke inhalation.

A 49-year-old man who sustained inhalational injury in a fire 23 years ago developed bronchiectasis 12 years later and hypercapnic respiratory failure with cor pulmonale 20 years following the injury. Delayed onset of chronic respiratory failure should be considered among the long-term complications of inhalational injury.

Bronchiectasis↗
PubMed1989

[Vasoactive intestinal peptide (VIP) protects against acid-induced acute lung injury in isolated perfused rat lungs].

Acute, diffuse lung injury, the principal lesion in ARDS, is often refractory to treatment. Recently, pretreatment with several pulmonary vasodilators that increase cAMP levels: isoproterenol, terbutaline, theophylline, and prostacyclin, was found to reduce the severity of lung injury in animal models. We have investigated the possible modulation of HCl-induced pulmonary edema in rats by VIP, a lung neuropeptide with potent vasodilator and cAMP-producing properties. The lungs of rats were perfused in situ at 10 ml/min with Krebs-4% albumin solution, and ventilated at constant tidal volume (6.5 ml/kg). Peak airway pressure (PAW), mean pulmonary arterial pressure (PPA) were measured throughout the experiment, and wet to dry lung weight ratio (W/D), afterwards. All animals were observed for one hour. In 6 rats receiving HCl only, 0.2 N-HCl was instilled intratracheally at 2 ml/kg. Four rats received 2 ml/kg of physiological saline intratracheally as control. In 6 other animals, VIP was infused into the pulmonary artery at 1 micrograms/kg/min, beginning 10 minutes before HCl and for the rest of the experiment. Another 6 rats were pretreated with atrial natriuretic peptide (ANP, atriopeptin II) just like the VIP group. Lungs of saline control animals showed little or no chage in PAW or PPA. With HCl alone, PAW increased immediately and continued to rise for the rest of the hour, reaching 500% of basal value at 30 minutes. PPA increased by 68% and W/D by 74% compared to saline-instilled lungs. In the VIP + HCl group, all abnormalities were significantly reduced relative to the HCl group. The rise in PAW was attenuated by 79% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

Human autoantibody to vasoactive intestinal peptide: increased incidence in muscular exercise.

Specific autoantibodies to vasoactive intestinal peptide were present in plasma from 29.6% healthy human subjects who habitually performed muscular exercise, compared to 2.3% healthy subjects who did not. Saturation analysis of VIP binding by the plasmas suggested the presence of 1 and 2 classes of autoantibodies in 5 and 3 high exercise subjects, respectively, distinguished by their equilibrium affinity constants (Ka). The mean Ka values for the high and low affinity autoantibody classes were, respectively, 1.3 x 10(8) M-1 and 0.8 x 10(7) M-1. These values are lower than the Ka range reported previously for tissue VIP receptors (G. Rosselin. Peptides 7, Suppl. 1, 89, 1986) but are larger than the inverse Michaelis constant (1/Km) for VIP-degrading proteases (T.N. Keltz, E. Straus, R.S. Yalow. Biochem. Biophys. Res. Commun. 92, 669, 1980). The autoantibodies may not interfere with VIP-receptor binding but are potential inhibitors of the proteolytic inactivation of VIP.

Adult↗
PubMed1988

Pharmacological evidence that the sympathetic nervous system mediates the increase in renin secretion produced by immobilization and head-up tilt in rats.

To determine the mechanism by which immobilization and head-up tilt under inactin anesthesia increase plasma renin activity (PRA), the effect of these stimuli on plasma levels of vasoactive intestinal polypeptide (VIP) were measured and the effect of the beta-adrenergic blocking drug, propranolol on the response of plasma renin activity determined. Increases in circulating VIP are known to stimulate secretion of renin. After 10 min of immobilization, plasma renin activity was increased and VIP in plasma was unchanged. After 30 min of tilting, plasma renin activity was also increased and VIP in plasma was unchanged. The increases in plasma renin activity were blocked by propranolol. Inactin anesthesia by itself increased plasma renin activity and this response was unaffected by propranolol and associated with a small decrease, rather than an increase in VIP in plasma. The results indicate that the responses of plasma renin activity to immobilization and head-up tilt are due to increased secretion of renin mediated by the sympathetic nervous system. On the other hand, the increase in secretion of renin produced by inactin anesthesia does not appear to be mediated by the sympathetic nervous system. There was no evidence that VIP was responsible for any of the increases.

Animals↗
PubMed1988

Co-localization of vasoactive intestinal peptide- and substance P-containing nerves in cat bronchi.

The occurrence of vasoactive intestinal peptide (VIP) and substance P in nerve fibers within the lung is well established, and both VIP- and substance P-containing nerve fibers are known to supply pulmonary vascular and bronchial smooth muscle and submucosal glands. In the present study, we have investigated the co-localization of these two peptides in cat lung. The co-localization procedure follows a standard immunocytochemical protocol except that the primary and labeled secondary antisera each contain a combination of two antisera allowing the simultaneous detection of two antigens in a single tissue section. Using fluorescence microscopy, VIP- and substance P-containing nerve fibers were co-localized in bronchial smooth muscle, in the walls of pulmonary and bronchial arteries, and around submucosal glands. VIP and substance P were also co-localized in nerve cell bodies that comprised the intrinsic airway ganglia. Substance P-containing nerve fibers were observed within the bronchial epithelium, but VIP was not present at this location. The co-localization of VIP and substance P in the same nerve fibers suggests that airway and pulmonary vascular function may be partially regulated by the simultaneous or sequential release of VIP and substance P from the same nerve fibers. The results also suggest that, in addition to extrinsic nerve fibers that contain substance P, the airways of cats are supplied by substance P-containing nerve fibers that originate from intrinsic nerve cell bodies.

Animals↗