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Biomedical subjects

S I Said

Publications and source records attributed to S I Said.

At least 91 records · Page 5Linked to original sources
PubMed1988

Autonomic innervation of pulmonary artery: evidence for a nonadrenergic noncholinergic inhibitory system.

We have investigated the presence and significance of the nonadrenergic noncholinergic relaxant system in isolated strips of guinea pig and cat pulmonary artery (PA), using transmural electrical field stimulation (EFS). Changes in PA strip tension were measured isometrically, in response to EFS with 50-70 V at 20 Hz and pulse durations of 1 or 2 ms. We examined the influence on these responses of alpha- and beta-adrenergic and cholinergic muscarinic receptor blockade, the neurotoxin tetrodotoxin, and the local anesthetic lidocaine. EFS induced an initial brief contraction followed by a slow prolonged relaxation. Phenoxybenzamine, 1.5 X 10(-5) M, greatly reduced the contraction (74.1-87.6% in guinea pig, 65.7-67.4% in cat) and enhanced the subsequent relaxation (23.9-35.5% in guinea pig, 66.8-67.8% in cat). The relaxation was moderately reduced by propranolol, 7.7 X 10(-6) M (30.5-35.0% in guinea pigs, 6.0-21.2% in cat), and by atropine, 1.4 X 10(-6) M (23.7-32.1% in guinea pig, 24.9-40.6% in cat). The major portion of the relaxation, however, persisted in the presence of these blockers. The neurogenic origin of this relaxation was confirmed by its loss with either tetrodotoxin or lidocaine. We conclude that in guinea pig and cat lungs (1) neurogenic pulmonary vascular contraction is principally mediated by the alpha-adrenergic system, (2) the beta-adrenergic and cholinergic components have a moderate relaxant influence, but (3) the dominant part of neurogenic relaxation is mediated by a nonadrenergic noncholinergic mechanism.

Animals↗
PubMed1988

Depression of lymphocyte traffic in sheep by vasoactive intestinal peptide (VIP).

Vasoactive intestinal peptide (VIP) is a 28 amino acid-residue neurovascular and gut peptide with a number of important biological activities. Recent in vitro studies suggest an immunomodulatory (depressant) role for VIP. In the present in vivo studies, employing the Hall and Morris sheep lymphocyte traffic model, acute infusions of VIP into cannulated afferent lymphatics of popliteal lymph nodes produced prompt and marked depressions in the output of both small recirculating and blast lymphocytes into popliteal efferent lymph, with a selective effect on T4 (CD4) lymphocytes. It has been suggested that the HIV (AIDS) virus may employ VIP or VIP-like receptors on brain cells and lymphocytes for intracellular access.

Animals↗
PubMed1987

Cardiovascular effects of vasoactive intestinal peptide in healthy subjects.

Hypotension and flushing are occasionally observed in patients with pancreatic cholera syndrome. Similar effects are produced when vasoactive intestinal polypeptide (VIP) is administered to healthy subjects. To characterize further these responses, serial measurements of heart rate, blood pressure, cardiac output and forearm blood flow were made in 6 healthy subjects during constant VIP infusion (400 pmol/kg/hr for 100 minutes). VIP infusion caused sustained vasodilatation and decreased total peripheral resistance and mean arterial pressure by 30 and 12%, respectively. Forearm resistance decreased by 65%. The effects on cardiac output and stroke volume were biphasic. During the early phase of VIP infusion (0 to 70 minutes), heart rate and cardiac output increased with only minor changes in stroke volume. Later (71 to 100 minutes) the tachycardia persisted, but cardiac output decreased toward control levels due to decreased stroke volume. Echocardiograms during the infusion demonstrated increased left ventricular contractility as defined by the relation between end-systolic wall stress and shortening fraction. These data document potent vasodilatory and inotropic actions of VIP. It is likely that intravascular volume losses from increased intestinal secretion account for the decreased stroke volume seen late in the VIP infusion period and immediately thereafter. The tachycardia appears to be an appropriate compensatory mechanism to maintain blood pressure in the presence of vasodilatation and loss of intervascular volume. These observations provide an explanation for the cardiovascular findings in patients with sudden release of VIP from tumors.

Adult↗
PubMed1987

Characterization of receptors for vasoactive intestinal peptide solubilized from the lung.

The zwitterionic detergent CHAPS was used to solubilize functional receptors for vasoactive intestinal peptide (VIP) from guinea pig lung. The solubilized receptors were resolved by high performance gel filtration in 3 mM CHAPS into two active fractions with apparent Stokes radii of 5.9 +/- 0.1 and 2.3 +/- 0.1 nm. The binding of 125I-VIP to the two receptor fractions was time-dependent, reversible, and saturable. Trypsin destroyed the binding activity of the receptor fractions, indicating their proteinic nature. Unlabeled VIP competitively displaced the binding of 125I-VIP to the 5.9-nm fraction (IC50 = 240 pM) and the 2.3-nm fraction (IC50 = 1.2 microM). Scatchard analysis indicated a single class of binding sites in each receptor fraction, with Kd values 300 pM and 0.97 microM for the 5.9- and 2.3-nm Stokes radii fractions, respectively. When the high affinity, 5.9-nm Stokes radius fraction was rechromatographed in 9 nM CHAPS, 46% of the binding activity eluted in the low affinity, 2.3-nm Stokes radius fraction, indicating that the latter is a product of dissociation of the high affinity receptor complex. GTP inhibited the binding of 125I-VIP to the high affinity complex but not the low affinity species. Scatchard plots of VIP binding by the high affinity receptors treated with GTP suggested the presence of two distinct binding sites (Kd 4.4 and 153 nM), compared to a single binding site (Kd = 0.3 nM) obtained in untreated receptors. The nonhydrolyzable GTP analog, guanyl-5'-yl-imidodiphosphate, inhibited VIP binding by the high affinity receptor fraction with potency nearly equivalent to that of GTP. These observations suggest that GTP-binding regulatory proteins are functionally coupled to the VIP-binding subunit in the high affinity receptor complex. The peptide specificity characteristics of the two receptor fractions were different. Peptide histidine isoleucine and growth hormone releasing factor, peptides homologous to VIP, were 87.5- and 22.9-fold less potent than VIP in displacing 125I-VIP binding by the high affinity receptor complex, respectively. On the other hand, growth hormone-releasing factor was more potent (22.7-fold) and peptide histidine isoleucine was less potent (31.3-fold) than VIP in displacing the binding by the low affinity species.

Animals↗
PubMed1987

Influence of neuropeptides on airway smooth muscle.

The first bronchoactive (and vasoactive) peptide to be discovered in the lung was isolated and characterized in 1970 from an embryologically related organ, the small intestine. Since then, more than 20 additional peptides have been described in lung tissue and their biologic activities investigated. Many of these are neuropeptides acting as neurotransmitters or neuromodulators to influence airway, pulmonary vascular, and other functions. More neuropeptides are known to exist in the brain and peripheral nervous system; at least some of these are soon likely to be identified in the lung. With the accelerated pace of research, the coming few years should see an increasing definition of the role of neuropeptides in lung physiology and pathophysiology, as well as in improved management of certain respiratory disorders.

Animals↗
PubMed1986

Solubilization of active receptors for VIP from guinea pig lung.

The zwitterionic detergent 3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propane sulfonate (CHAPS) was used to solubilize functional receptors for vasoactive intestinal peptide (VIP) from guinea pig lung. The binding of [125I]-VIP to the soluble receptors was time-dependent, reversible and saturable. Trypsin destroyed the activity of the receptors, indicating their proteinic nature. Dithiothreitol reduced the binding in a dose-dependent manner, suggesting the importance of disulfide bond(s) in receptor-binding activity. Binding of [125I]-VIP to the receptors was reversible and was competitively inhibited by unlabeled VIP, with 50% inhibition obtained at 305 nM VIP.

Animals↗
PubMed1986

Receptors for vasoactive intestinal peptide on isolated human sweat glands.

Human sweat gland function is predominantly under cholinergic control. Sweat secretion may also be regulated by Vasoactive Intestinal Peptide (VIP), which coexists with acetylcholine in nerves to sweat gland acini and ducts. We have examined the expression of VIP receptors on isolated human eccrine sweat glands. Two classes of specific binding sites for VIP were demonstrated: one with high affinity (Kd = 0.58-2.4 nM), and another with low affinity (Kd = 175-288 nM). The data suggest a physiological regulatory role for VIP in sweat gland function.

Eccrine Glands↗
PubMed1986

Vasoactive intestinal polypeptide relaxes pulmonary artery by an endothelium-independent mechanism.

Vasoactive intestinal polypeptide (VIP) is a potent endogenous vasodilator. VIP-induced vasodilation is independent of adrenergic or cholinergic receptors and, for the most part, of arachidonate metabolites, but its mechanism is still unknown. In view of the recently demonstrated essential role of endothelium in the relaxant effect of numerous vasodilators, we have investigated the importance of endothelium in the vascular relaxation induced by VIP. Vascular smooth muscle preparations were circular strips of the pulmonary artery of guinea pig, rat and rabbit, and rat thoracic aorta, previously contracted by a synthetic prostaglandin endoperoxide analog. VIP relaxed pulmonary artery of all species by an endothelium-independent mechanism, but relaxed rat thoracic aorta only in the presence of intact endothelium.

Animals↗
PubMed1986

In vitro evidence that vasoactive intestinal peptide is a transmitter of neuro-vasodilation in the head of the cat.

Experiments have been undertaken to determine the nature of the atropine-resistant neurogenic dilation that can be demonstrated in vitro in cephalic arteries of the cat. Levels of vasoactive intestinal peptide (VIP) and substance P were measured in a number of arteries and related to the extent of the neurogenic dilation that can be elicited in vitro. There is no correlation between the tissue contents of the two peptides. A positive correlation was found between vasoactive intestinal peptide but not substance P content and neurogenic dilation. Vasoactive intestinal peptide but not substance P consistently caused a concentration-dependent dilation of cephalic arteries not subject to significant tachyphylaxis. Vasoactive intestinal peptide antiserum in concentrations that block the dilation to vasoactive intestinal peptide (10(-6) M) but not that due to papaverine, significantly reduced neurodilation of both atropinized and non-atropinized lingual arteries--the cephalic artery with the highest VIP content. These results suggest that vasoactive intestinal peptide and not substance P significantly contributes to the non-cholinergic neurogenic dilation observed in vitro in arterial segments from the head of the cat.

Animals↗
PubMed1985

Deficient vasoactive intestinal peptide innervation in the sweat glands of cystic fibrosis patients.

The innervation of acini and ducts of eccrine sweat glands by immunoreactive, vasoactive intestinal peptide-containing nerve fibers was sharply reduced in seven patients with cystic fibrosis compared to eight normal subjects. The decrease in innervation by this neuropeptide, which has been shown to promote blood flow and the movement of water and chloride across epithelial surfaces in other systems, may be a basic mechanism for the decreased water content and relative impermeability of the epithelium to chloride and other ions that characterize cystic fibrosis.

Adolescent↗
PubMed1985

Autoantibody to vasoactive intestinal peptide in human circulation.

In a radioassay for Vasoactive Intestinal Peptide (VIP)-binding, eight out of 33 plasma samples from healthy human subjects exhibited specific binding ranging from 2.6% to 46.7% of total [125 I]VIP. This binding was competitively displaced by unlabeled VIP. The structurally homologous peptides, Peptide Histidine Isoleucine (PHI) and secretin, were, respectively, 72-fold and 413-fold less potent than VIP in displacing bound [125 I]VIP, whereas the unrelated peptides, neurotensin, eledoisin, bombesin and metenkephalin, were without effect on the binding. The antibody nature of the VIP-binding factor was suggested by its precipitation with ammonium sulfate, attenuation after absorption with Staphylococcus aureus preparations, precipitation with antisera against human IgG and IgM, and coelution with standard IgG and IgM on anion-exchange and high-performance gel-filtration columns. Pepsin treatment of purified IgG fraction yielded a VIP-binding species with apparent molecular weight of 108 +/- 13 kDa that was precipitated by antiserum against the F(ab)2 fragment of the IgG molecule. These results demonstrate the existence in some human plasmas of an autoantibody that binds VIP.

Antibody Specificity↗
PubMed1985

Localization of vasoactive intestinal peptide immunoreactivity in human foetus and newborn infant spinal cord.

Using an indirect immunofluorescence method the distribution of vasoactive intestinal peptide (VIP) immunoreactivity was studied in human foetus and newborn infant spinal cord and dorsal root ganglia. Further, for comparison some newborn infant brains were also investigated. Vasoactive intestinal peptide-like immunoreactive fibres were exclusively found in the caudal spinal cord and corresponding dorsal root ganglia. No immunoreactive cell bodies were detected. The first appearance of VIP-like immunoreactive fibres in both spinal cord and dorsal root ganglia was suggested during the fourth month of foetal life. Most immunolabelled fibres, concentrated in the sacral segment, were distributed in the Lissauer tract, along the dorsolateral gray border, in the intermediolateral areas and near the central canal in the dorsolateral commissure. A few VIP-like immunoreactive fibres were also seen in the dorsal funiculus and occasionally in the ventral gray horn and ventral roots. Further, a large population of VIP-like immunoreactive fibres occurs longitudinally in dorsal root, in ganglia and in the spinal nerve exit zone. These findings indicate the early appearance of VIP-like immunoreactive fibres in the human foetus spinal cord and corresponding ganglia. Moreover, they emphasize that in both foetus and newborn infant spinal cord VIP-like immunoreactive fibre distribution is limited to the lumbosacral segment.

Fluorescent Antibody Technique↗
PubMed1985

Vasoactive intestinal peptide as a neural mediator of gastric relaxation.

Two main candidates, adenosine 5'-triphosphate (ATP) and vasoactive intestinal peptide (VIP), have been proposed as inhibitory transmitters at neuromuscular junctions in the gut. We have used a photoaffinity analogue of ATP, 3'-O-(4-benzoyl)benzoyl ATP or BzATP, that binds covalently to ATP receptors and inactivates them in the presence of light and a specific high-affinity VIP antiserum in order to examine the contributions of ATP and VIP to neurally induced relaxation in circular smooth muscle of the gastric fundus of the guinea pig. VIP and ATP caused dose-dependent relaxation; the effect of ATP was equal to that of its stable isostere, alpha, beta-methylene ATP, and was resistant to degradation by adenosine deaminase, indicating interaction of ATP with purinergic P2-receptors. Relaxation induced by VIP was selectively inhibited by VIP antiserum (final dilution 1:120), while that induced by ATP was selectively inhibited by photoactivated BzATP. Relaxation induced by electrical field (i.e., neural) stimulation was inhibited by VIP antiserum only; photoactivated BzATP had no effect. Inhibition of neurally induced relaxation ranged from 86% (P less than 0.01) at the lowest frequencies to 34% (P less than 0.01) at the highest frequencies. Maximal field stimulation caused an 11-fold increase in VIP release from intramural neurons. The results strongly favor VIP as the neural mediator of gastric relaxation.

Adenosine Triphosphate↗
PubMed1985

Vasoactive intestinal peptide in the regulation of renin secretion.

We have previously shown that vasoactive intestinal peptide (VIP) is a renin-stimulating factor both in vivo and in vitro. In the present investigation we sought to determine whether VIP exerted this effect by a neural or humoral mechanism. To test for a neural effect, the renal nerves were stimulated on one side for 30 min in anesthetized dogs, and plasma VIP and renin levels were determined in the renal venous effluent. The stimulation significantly increased plasma renin activity in arterial and renal venous plasma but had no effect on VIP concentrations. A humoral action was tested in two ways. First, plasma renin activity was measured before and after elevating circulating levels of endogenously produced VIP using intravenous neostigmine (0.07 mg/kg) in control, renal-denervated, and propranolol-pretreated animals. In all three groups, the elevated plasma level of VIP was associated with a significant increase in plasma renin activity. Second, plasma levels of VIP were determined in conscious dogs with elevated plasma renin activity produced by either a low-salt diet or hemorrhage. In both cases, plasma renin activity was significantly elevated as expected, but plasma levels of VIP were unchanged. These data suggest that the effects of VIP on renin secretion are not mediated by release of the peptide from the renal nerves, the circulating level of endogenously produced VIP can be elevated sufficiently to stimulate renin secretion, but a humoral role of VIP in the elevated plasma renin activity produced by low-salt diet or hemorrhage seems unlikely.+

Animals↗
PubMed1985

Pulmonary vasodilator responses to vasoactive intestinal peptide in the cat.

We investigated the effects of vasoactive intestinal peptide (VIP) in the feline pulmonary vascular bed under conditions of controlled pulmonary blood flow when pulmonary vascular tone was at base-line levels and when vascular resistance was elevated. Under base-line conditions, VIP caused small but significant reductions in lobar arterial pressure without affecting left atrial pressure. Decreases in lobar arterial pressure in response to VIP were greater and were dose related when lobar vascular resistance was increased by intralobar infusion of U 46619, a stable prostaglandin endoperoxide analogue. Acetylcholine and isoproterenol also caused significant decreases in lobar arterial pressure under base-line conditions, and responses to these agents were enhanced when lobar vascular tone was elevated. Moreover, when doses of these agents are expressed in nanomoles, acetylcholine and isoproterenol were more potent than VIP in decreasing lobar arterial pressure. Responses to VIP were longer in duration with a slower onset than were responses to acetylcholine or isoproterenol. Pulmonary vasodilator responses to VIP were unchanged by indomethacin, atropine, or propranolol. The present data demonstrate that VIP has vasodilator activity in the pulmonary vascular bed and that responses are dependent on the existing level of vasoconstrictor tone. These studies indicate that this peptide is less potent than acetylcholine or isoproterenol in dilating the feline pulmonary vascular bed and that responses to VIP are not dependent on a muscarinic or beta-adrenergic mechanism or release of a dilator prostaglandin.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗