Sphingosine 1-phosphate stimulates cell migration through a G(i)-coupled cell surface receptor. Potential involvement in angiogenesis.

Sphingosine 1-phosphate (SPP) has been shown to inhibit chemotaxis of a variety of cells, in some cases through intracellular actions, while in others through receptor-mediated effects. Surprisingly, we found that low concentrations of SPP (10-100 nM) increased chemotaxis of HEK293 cells overexpressing the G protein-coupled SPP receptor EDG-1. In agreement with previous findings in human breast cancer cells (Wang, F.

Blood pressure, plasma NPY and catecholamines during physical exercise in relation to menstrual cycle, ovariectomy, and estrogen replacement.

Some evidences indicate that the female sex hormones protect against the development of cardiovascular diseases. Modulation of sympathetic activity may be one of the possibilities. We investigated the influence of treadmill stress on blood pressure (BP) and plasma neuropeptide Y (NPY), norepinephrine (NE) and epinephrine (E) concentrations in 11 normotensive, menstruating women in the follicular (HWf) and luteal (HWl) phases and in eight ovariectomized women, before (OVX) and after estrogen supplementation (OVXe).

Mechanisms of vascular growth-promoting effects of neuropeptide Y: role of its inducible receptors.

We have previously reported that neuropeptide Y (NPY), a sympathetic cotransmitter and vasoconstrictor, is mitogenic for vascular smooth muscle cells (VSMCs), and now report on the mechanisms mediating these effects. In rat aortic A10 cell line, NPY's potency was greater than that of norepinephrine, and efficacy similar to that of platelet-derived growth factor, but less than that of the full serum, in stimulating cell proliferation; this effect was optimal in cell 60-80% cell density. At lower cell density and serum content, NPY stimulated DNA fragmentation/apoptosis.

Endogenous neuropeptide Y mediates vasoconstriction during endotoxic and hemorrhagic shock.

Neuropeptide Y (1-36), NPY, is a sympathetic vasoconstrictor whose activities in blood vessels is determined by the presence of vasoconstrictive Y1 receptors and the enzyme dipeptidyl peptidase IV (DPPIV), which converts NPY to non-vasoconstrictive peptides. While the role of the NPY system has been established during cold water stress, its role in hypotensive conditions has not; yet, exogenous NPY improves hemodynamics and survival in rats with endotoxic shock. We used a new selective non-peptidergic Y1 receptor antagonist, BIBP-3226, to determine the role of the endogenous NPY/Y1 system in endotoxic shock (induced by i.

HIV envelope protein gp120 induces neuropeptide Y receptor-mediated proliferation of vascular smooth muscle cells: relevance to AIDS cardiovascular pathogenesis.

Hyperplasia of vascular smooth muscle cells (VSMCs) occurs during HIV infection, part of a spectrum of HIV-mediated cardiovascular and microvascular pathologies. These changes are not due to direct viral infection but may involve the receptor-mediated action of viral proteins, such as the envelope protein gp120. We sought to identify gp120 receptors which might mediate the vascular smooth muscle cell hyperplasia present in HIV infection.

Alterations in plasma neuropeptide Y immunoreactivity and catecholamine levels during surgical removal of pheochromocytoma.

Background: Neuropeptide Y, an abundant neurohormone present with catecholamines in the adrenal medulla, is a potent non-adrenergic vasoconstrictor and a vascular growth factor.

Objective: To determine the mechanism of the release from, and possible role of neuropeptide Y in, pheochromocytomas, compared with those of catecholamines.

Methods: Plasma and tumour levels of neuropeptide Y-immunoreactivity (by, radioimmunoassay) and of noradrenaline and adrenaline (by a radioenzymatic method) in 29 patients (19 women and 10 men, aged 22-68 years) were measured during surgical removal of the tumour, during alpha-adrenergic and beta-adrenergic blockade.

Neuropeptide Y: a novel angiogenic factor from the sympathetic nerves and endothelium.

Sympathetic nerves have long been suspected of trophic activity, but the nature of their angiogenic factor has not been determined. Neuropeptide Y (NPY), a sympathetic cotransmitter, is the most abundant peptide in the heart and the brain. It is released during nerve activation and ischemia and causes vasoconstriction and smooth muscle cell proliferation.

Circulating neuropeptide Y in humans: relation to changes in catecholamine levels and changes in hemodynamics.

Neuropeptide-Y (NPY) is a sympathetic cotransmitter, which causes vasoconstriction, decreases coronary blood flow and decreases cardiac output. Circulating immunoreactive NPY (ir-NPY) levels increase with exercise, in patients admitted to the coronary care unit, and during thoracic surgery, and may play a role in postoperative hemodynamics. We studied changes in ir-NPY, epinephrine (E) and norepinephrine (NE) arterial plasma levels, and their correlation to simultaneous hemodynamic measurements at 8 perioperative time points in 13 patients undergoing open heart surgery.

Stress-induced mesenteric vasoconstriction in rats is mediated by neuropeptide Y Y1 receptors.

The physiological role of neuropeptide Y (NPY), a sympathetic cotransmitter and vasoconstrictor, has not been determined yet. We used a specific nonpeptide antagonist to the NPY Y1 receptor [BIBP-3226; (R)-N2-(diphenacetyl)-N-[(4-hydroxyphenyl) methyl]-D-arginineamide] to study the involvement of NPY in stress-induced vasoconstriction in the mesenteric bed. In rats subjected to cold water stress (COLD), plasma NPY immunoreactivity levels increased progressively from 0.

Neuropeptide Y. A novel sympathetic stress hormone and more.

Several lines of evidence suggest that NPY is a neurotransmitter and neurohormone intricately involved in stress responses of the body, and as such should be considered a "stress molecule." Thus, circulating plasma NPY levels are increased by stress particularly if it is severe or prolonged. Stress stimulates the release of NPY from the sympathetic nerves and the adrenal medulla (in some species also from platelets), and in addition, modulates NPY inactivation.

Effect of pentobarbital anesthesia on the pressor response to agonists in vivo in normal and endotoxemic rats.

Studies of cardiovascular physiology are frequently performed under barbiturate anesthesia even though the effect of barbiturates on the pressor response to catecholamines is controversial, and their effect on the response to other agonists is unknown. The effect of pentobarbital (PB) anesthesia on the pressor and heart rate (HR) dose responses to norepinephrine (NE), angiotensin II (AII), vasopressin (VP) and neuropeptide Y (NPY) was studied in vivo in normal and endotoxemic rats. Four groups of rats (5-6 rats/group) were studied for each agonist: 1) anesthetized/endotoxemic, 2) anesthetized/control, 3) conscious/endotoxemic, and 4) conscious/control.

Plasma neuropeptide Y and catecholamines in women and men with essential hypertension.

Neuropeptide-Y (NPY) is a peptide proposed to modulate the effect of the sympathetic nervous system on blood pressure control and contribute to the development of essential hypertension. To assess the possible influence of gender on its role, we evaluated plasma NPY, noradrenaline (NA) and adrenaline (A) concentrations in men and women with essential hypertension. No difference in NPY concentration was found between genders, but NPY concentration was elevated in both hypertensive men and women.

Contribution of alpha- and beta- adrenoceptors and neuropeptide-Y to autonomic dysreflexia.

Modest increases in urinary bladder pressure result in acute hypertensive episodes in humans with spinal cord lesions above T5. The underlying mechanisms of this condition, referred to as autonomic dysreflexia, are not well understood. The aim of this study was to characterize the contribution of alpha- and beta-adrenoceptors as well as circulating neuropeptide-Y (NPY) to the pressor response to bladder distension in conscious cervical spinal rats.

Effect of neuropeptide Y on endotoxin-induced suppression of the response to various agonists in conscious rats.

Hypotension during endotoxic shock is related to reduced vascular responsiveness to vasoconstrictors. Neuropeptide Y (NPY) is known to potentiate the pressor response to some agonists, and NPY infusion has been shown to improve hemodynamics and survival in endotoxemic rats. We therefore studied the effect of NPY infusion on the suppressed pressor effect of norepinephrine (NE), angiotensin II (AII), vasopressin (VP), and endothelin (ET) in conscious endotoxemic rats.

Neuropeptide Y and alpha-adrenoceptor interactions in patients with essential hypertension.

Neuropeptide Y (NPY) is a vasoconstrictor sympathetic cotransmitter and a modulator of adrenergic function whose role in hypertension is yet unknown. We studied the co-release of NPY and noradrenaline (NA) in patients with essential hypertension (13 females, 11 males, age 42 +/- 13 years) by measuring plasma levels of NPY-immunoreactivity (-ir, radioimmunoassay) and NA (radioenzymatic method) following administration of clonidine (CL 300 micrograms, p.o.

Modulation of vascular function by neuropeptide Y during development of hypertension in spontaneously hypertensive rats.

Neuropeptide Y (NPY) is a sympathetic cotransmitter and a platelet-derived factor which causes vasoconstriction, potentiation of norepinephrine (NE) action, and vascular mitogenic effects. Reciprocally, NE markedly enhances the actions of NPY. We studied vasopressor effects of NPY and sources of peptide release during the development of hypertension in spontaneously hypertensive rats (SHR).

Neuropeptide Y infusion improves hemodynamics and survival in rat endotoxic shock.

Neuropeptide Y (NPY), a sympathetic and platelet-derived vasoconstrictor, acts both directly and by potentiating adrenergic responsiveness and therefore may be beneficial in endotoxic shock, where suppressed vascular responsiveness to adrenergic agents is a key factor. This was studied in anesthetized rats. First, infusion of a nonhypotensive dose of endotoxin (lipopolysaccharide, LPS) markedly suppressed the pressor response to increasing doses of norepinephrine (NE), angiotensin II, and vasopressin but did not suppress the response to NPY.

Immunoreactive neuropeptide Y (NPY) in plasma and platelets of rat and mouse strains and human volunteers.

Immunoreactive-neuropeptide Y (i-NPY) is present in platelets of rats, and has recently been demonstrated to be authentic rat NPY based on its amino acid sequence. This potent vasoconstrictor and putative smooth muscle mitogen is released during platelet activation, suggesting a role in platelet-vascular interactions. We have now extended this work to several strains of rats and mice, and humans of both sexes.

Influence of cigarette smoking on human autonomic function.

Background: Although cigarette smoking is known to lead to widespread augmentation of sympathetic nervous system activity, little is known about the effects of smoking on directly measured human sympathetic activity and its reflex control.

Methods And Results: We studied the acute effects of smoking two research-grade cigarettes on muscle sympathetic nerve activity and on arterial baroreflex-mediated changes of sympathetic and vagal neural cardiovascular outflows in eight healthy habitual smokers. Measurements were made during frequency-controlled breathing, graded Valsalva maneuvers, and carotid baroreceptor stimulation with ramped sequences of neck pressure and suction.

Mitogenic effect of neuropeptide Y in rat vascular smooth muscle cells.

Neuropeptide Y (NPY) is a vasoconstrictor released with norepinephrine from perivascular sympathetic nerves. Since sympathetic nerves appear to play a role in vascular smooth muscle cell (SMC) hypertrophy, we studied the effects of NPY on proliferation of cultured rat aorta- and vena cava-derived SMC. Both cell types displayed high-affinity NPY binding sites with displacement characteristics of [Pro34]NPY > NPY(13-36) > NPY(18-36) in aorta and [Pro34]NPY = NPY(13-36) = NPY(18-36) in the vena cava.

Blood pressure responses to sucrose ingestion in four rat strains.

Among four strains examined, spontaneously hypertensive rats (SHR) show a marked (20 mm Hg, P less than .01) systolic blood pressure elevation (SBP), Sprague-Dawley (SD) and Wistar-Kyoto (WKY) rats developed a moderate elevation (8 mm Hg, P less than .01), and a normotensive Wistar rat (WAM) had a lesser SBP elevation (6 mm Hg, P = NS) after excess sucrose ingestion.

Cardiovascular effects of omega-conopeptides in conscious rats: mechanisms of action.

We examined the effects of omega-conopeptides, a novel class of neuronal voltage-gated calcium channel antagonists, on hemodynamic responses in rats. Intravenous (i.v.

C-terminal neuropeptide Y fragments are mast cell-dependent vasodepressor agents.

Neuropeptide Y (NPY) is a well-established vasopressor agent present in sympathetic perivascular nerves. Recently, it was found that high doses of the peptide cause a biphasic pressor-depressor response upon intravenous administration. We now report that C-terminal NPY fragments (NPY-(18-36) and NPY-(22-36] given intravenously to conscious or pithed (areflexive) male Sprague-Dawley rats mimic the depressor component of the NPY-(1-36) response while displaying very low pressor activity.