Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Noradrenergic neurons in the locus ceruleus contain neuropeptide Y and galanin, which project to the hypothalamic region. We have investigated the regulatory mechanisms of these peptides on norepinephrine release in rat hypothalamic slices in vitro. Neuropeptide Y and galanin significantly inhibited the stimulation-evoked [3H]norepinephrine release in a dose-dependent manner (1 Hz: S2/S1 ratio (mean +/- SEM), control 0.947 +/- 0.040, n = 11, neuropeptide Y 1 x 10(-8) M 0.509 +/- 0.013, n = 8, p less than 0.01, neuropeptide Y 1 x 10(-7) M 0.283 +/- 0.021, n = 8, p less than 0.01; galanin 1 x 10(-7) M 0.448 +/- 0.026, n = 8, p less than 0.01, galanin 1 x 10(-6) M 0.261 +/- 0.023, n = 8, p less than 0.01). The inhibition of norepinephrine release by the alpha-2 agonist UK 14,304 was potentiated by neuropeptide Y and galanin. The blockade of the alpha 2-adrenergic receptors by RX 781094 diminished the inhibitory effects of neuropeptide Y and galanin on norepinephrine release. Pretreatment of hypothalamic slices with islet activating protein (a toxin that interferes with the coupling of inhibitory receptors to adenylate cyclase) attenuated the suppression of norepinephrine release by UK 14,304, neuropeptide Y, and galanin. These results support the idea that neuropeptide Y and galanin are involved in the regulation of central adrenergic transmission partially mediated by alpha 2-adrenergic receptors and islet-activating protein-sensitive guanosine triphosphate-binding proteins in rat hypothalamus.
Hypertension 1989 Jul
PMID:Neuropeptide Y and galanin in norepinephrine release in hypothalamic slices. 247 59

The field stimulation induced release of 3H-norepinephrine (NE) from the isolated portal vein and endogenous NE from the isolated caudal artery and perfused mesenteric arterial bed of spontaneously hypertensive rats (SHR) and age-matched normotensive rats (Wistar-Kyoto or Sprague-Dawley) was studied. There was a significantly greater release of NE from all three preparations obtained from 10- to 12-week-old SHR compared to normotensive animals. In addition, there was a greater release of NE from the caudal artery of 5- to 6-week-old SHR compared to controls. No differences were seen in the evoked release of NE from portal vein or caudal artery obtained from renal or DOCA salt hypertensives compared to vessels obtained from sham controls. Neuropeptide Y (NPY) produced a concentration-dependent decrease in the field stimulation induced release of NE from the perfused mesenteric artery. Low concentrations of NPY decreased while higher concentrations potentiated the increase in perfusion pressure. The NPY induced inhibition of evoked NE release was not altered by alpha 1- or alpha 2-adrenoceptor antagonists while the alpha 1-adrenoceptor antagonist, prazosin, prevented the postjunctional response. These results are consistent with there being an alteration of NE release at the vascular neuroeffector junction in SHR which may contribute to the development or maintenance of hypertension. NPY exerts a modulatory role in noradrenergic transmission at the vascular neuroeffector junction.
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PMID:Alterations in the release of norepinephrine at the vascular neuroeffector junction in hypertension. 359 78

Neuropeptide Y content of the kidneys, heart, blood vessels, adrenals and brain stem was determined in both two-kidney, one-clip and one-kidney, one-clip Goldblatt hypertension in rats and compared with levels in age- and sex-matched controls. Renal neuropeptide Y content was significantly reduced in the clipped kidney of rats in both Goldblatt two-kidney, one-clip and Goldblatt one-kidney, one-clip models of hypertension. The content of neuropeptide Y was also reduced but to a lesser extent in the contralateral, non-ischaemic kidney in the two-kidney, one-clip model. In both models of hypertension, neuropeptide Y content in the heart was significantly reduced in the left ventricle and septum but unchanged in the atria and right ventricle wall. There was no significant change in the concentration of neuropeptide Y through the vasculature (major arteries and veins), including the renal artery distal to the clip, or in adrenals and brain stem.
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PMID:Neuropeptide Y in renovascular models of hypertension in the rat. 375

Neuropeptide Y (NPY) is a 36-amino acid peptide belonging to the pancreatic polypeptide family that has marked and diverse biological activity across species. NPY originally was isolated from mammalian brain tissue somewhat more than 10 years ago and, since that time, has been the subject of numerous scientific publications. NPY and its proposed three receptors (Y1, Y2 and Y3) are relatively abundant in and uniquely distributed throughout the brain and spinal cord. This review will highlight the results from a number of research-oriented studies that have examined how NPY is involved in CNS function and behavior, and how these studies may relate to the possible development of medicines, either NPY-like agonists or antagonists, directed towards the treatment of disorders such as anxiety, pain, hypertension, schizophrenia, memory dysfunction, abnormal eating behavior and depression.
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PMID:Central nervous system pharmacology of neuropeptide Y. 764 68

Neuropeptide Y has been shown to inhibit contractility in the rat heart. Although the reasons for this effect are not known, it is possible that postsynaptic adrenergic mechanisms involving neuropeptide Y may be responsible. To ascertain whether this neuromodulatory effect is possible for decreasing contractility, we investigated the effect of neuropeptide Y on agonist-stimulated contractility of the isolated rat myocardium. Receptor binding studies of purified cardiac membranes showed that incubating membrane in the presence of neuropeptide Y (10(-7) mol/L) decreased the number of alpha-/beta-adrenoceptor binding sites without affecting the affinity of these receptors. Isolated hearts perfused with phenylephrine (10(-5) to 10(-10) mol/L) or isoproterenol (10(-5) to 10(-10) mol/L) in a nonrecirculating Langendorff setup demonstrated a significant increase in contractility over control values, whereas no change in contractility was observed when the hearts were perfused with neuropeptide Y (10(-7) mol/L). However, in the presence of both agonist and neuropeptide Y the increase in contractility previously seen with agonist alone was not evident. Comparisons made with hearts taken from aortic banded rats yielded similar results. Although neuropeptide Y itself was ineffective in decreasing contractility, it prevented the agonists from stimulating contractility when perfused together. We conclude that neuropeptide Y does not directly decrease contractility but prevents agonist-stimulated increases in contractility through alpha-/beta-adrenoceptor pathways. This neuromodulatory effect of neuropeptide Y is unchanged in situations of increased sympathetic activity, such as hypertension.
Hypertension 1995 Sep
PMID:Neuropeptide Y prevents agonist-stimulated increases in contractility. 764 85

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.). At rest, only NPY-ir levels significantly correlated with diastolic blood pressure (DBP, r = 0.42, p < 0.05). Three hours after CL, there were a decrease in mean arterial pressure and plasma NA (by 31 +/- 14 mmHG, p < 0.05 and 92 +/- 10 pg/ml, p < 0.01) but no change in NPY-ir levels. Patients were subsequently subdivided into groups with high (> or = 90 mmHg) or normal DBP (< or = 89 mmHg) and with or without elevated plasma NA levels (above or below 414 pg/ml, a normotensive mean +1 standard deviation). In hypertensives, but not in those with normal DBP, plasma NPY-ir correlated not only with DBP but also with systolic and mean blood pressure (r = 0.53 and r = 0.60, respectively) at rest. Hypertensives with "high" NA had significantly lower resting plasma NPY-ir levels than those with "low" NA (7.1 +/- 3.6 vs 14.7 +/- 6.0 fmol/ml, p < 0.05). In the former group, CL evoked the greatest fall in plasma NA, and also decreased NPY-ir levels by 50% (p < 0.05). Thus, patients with essential hypertension were found to display differential patterns of changes in sympathetic cotransmitters to clonidine. NPY may contribute to the increased blood pressure in hypertensives and together with NA, mediate hypotensive action of clonidine but only in the hyperadrenergic subgroup of hypertensives.
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PMID:Neuropeptide Y and alpha-adrenoceptor interactions in patients with essential hypertension. 766 76

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). Conscious SHR (4 and 16 weeks old) had higher resting plasma levels of NE and epinephrine than age-matched Wistar-Kyoto (WKY) rats, but similar NPY immunoreactivity (NPY-ir) levels in platelet-poor plasmas (PPP). In both strains, NPY-ir levels in PPP were higher in 4-week-old than in older rats. However, at all ages (4-24 weeks) SHR had markedly elevated NPY-ir content in platelet-rich-plasmas than WKY rats, although levels declined with age and hypertension. In the superior mesenteric artery, NPY-ir content (per mg) was significantly higher in 4-week-old but lower in 16-week-old SHR than in WKY rats, suggesting greater sympatho-neural NPY stores and release (leading to depletion) during the development of hypertension. Four-week-old SHR also tended to have higher NPY-ir content in the adrenal medullae and coeliac ganglia but a lower content in the kidney than WKY rats; these differences disappeared with age. Pressor responsiveness to alpha-agonists and NPY were similar in both strains at 4 weeks. While unchanged by age in WKY rats, adrenergic and NPY-mediated vasopressor responses became augmented in 16- to 24-week-old SHR (compared with WKY rats); this hyperresponsiveness was not completely abolished by ganglionic blockade and not observed with vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of vascular function by neuropeptide Y during development of hypertension in spontaneously hypertensive rats. 790 99

Neuropeptides are ubiquitous in the sympathetic system and modulate transmission at the levels of the intermediolateral cell column, sympathetic ganglia, and neuroeffector junctions. Several neuropeptide-containing pathways from the hypothalamus and medulla modulate excitability of preganglionic neurons. Neuropeptides coexist with norepinephrine or acetylcholine in subpopulations of chemically coded, target-specific sympathetic ganglion neurons. Neuropeptide Y is colocalized in adrenergic vasoconstrictor neurons, whereas vasoactive intestinal polypeptide is colocalized in cholinergic sudomotor neurons. Neuropeptide expression is plastic; during development, neurons that switch from a noradrenergic to a cholinergic phenotype increase expression of vasoactive intestinal polypeptide, somatostatin, and substance P. Preganglionic inputs increase neuropeptide Y and inhibit substance P expression. Sympathetic denervation produces sprouting of sensory fibers containing substance P and calcitonin gene-related peptide in target tissues. Neuropeptides from preganglionic fibers (e.g., enkephalin) and primary afferents (e.g., substance P, vasoactive intestinal polypeptide) modulate transmission in sympathetic ganglia. Neuropeptide Y produces vasoconstriction, prejunctional inhibition of norepinephrine release, and postjunctional potentiation of norepinephrine effects. Plasma neuropeptide Y increases during intense sympathoexcitation, hypertension, and pheochromocytoma. Dystrophic neurites containing neuropeptide Y occur in human sympathetic ganglia during aging, diabetes, and dysautonomia. Sympathetic neuropeptides may thus have important clinical implications.
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PMID:Neuropeptides in the sympathetic system: presence, plasticity, modulation, and implications. 802 63

1. Neuropeptide Y (NPY) occurs in both the central and peripheral nervous system. In the periphery, NPY coexists with noradrenaline (NA) in perivascular sympathetic fibers. 2. NPY has a vasopressor effect, reflecting direct vasoconstriction of blood vessels and potentiation of the NA-evoked response. NPY also suppresses the release of NA from sympathetic fibers. 3. The post- and pre-junctional NPY receptors are referred to as Y1 and Y2, respectively. They recognize not only NPY but also the homologous gut hormone peptide YY (PYY). 4. The Y1 and Y2 receptors have been characterized in numerous test systems using analogs of NPY/PYY. Already the deletion of the first N-terminal amino acid (NPY 2-36) results in a marked loss of potency at the Y1 receptor. The Y2 receptor is much less dependent upon an intact N-terminus, and a wide range of C-terminal NPY fragments retain quite high potency. 5. Recently, yet another NPY receptor, Y3, that is distinct from Y1 and Y2 in that it recognizes PYY poorly, has been demonstrated in the brainstem and in the periphery. 6. Further attempts to characterize the various receptor types have relied on truncated and substituted analogs of NPY/PYY. Although such studies suggest the existence of at least three types of NPY receptors, the lack of antagonists has represented a problem. 7. Since NPY may regulate cardiovascular functions via peripheral and central receptors its physiological and possibly pathophysiological significance has attracted much attention. 8. The responsiveness to NPY seems to be altered in animal models of hypertension and elevated plasma levels of NPY have been found in patients under various conditions of stress and in primary hypertension. A number of studies have suggested that NPY may be a pathogenetic factor behind primary hypertension. 9. Antagonists for the various NPY receptors would be useful for an analysis of which effects of these peptides are physiologically relevant. It is tempting to predict that both agonists and antagonists of the NPY receptors could be useful as drugs, for instance, in the treatment of primary hypertension.
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PMID:Multiple neuropeptide Y receptors are involved in cardiovascular regulation. Peripheral and central mechanisms. 822 32

Neuropeptide Y is a cotransmitter in the sympathetic nervous system with potent contractile effects on blood vessels. The plasma levels of neuropeptide Y-like immunoreactivity in patients with severe hypertension (> 120 mmHg) were increased compared with the levels in control subjects and were still elevated after long-term pharmacologic treatment of normotension. Neuropeptide Y stimulated DNA synthesis, total cell number, and total protein production in human vascular smooth muscle cells through a Y1-receptor. A Gi/G(o)-coupled second messenger mechanism seems to be involved, because pretreatment with pertussis toxin abolished the mitogenic effect. Neuropeptide Y potentiated the mitogenic effect of noradrenaline, and together with adenosine 5'-triphosphate, the sympathetic cotransmitters reached a mitogenic effect of approximately 20% of fetal calf serum. We have shown that neuropeptide Y, noradrenaline, and adenosine 5'-triphosphate, apart from their effects on vascular tone, are stimulators of vascular smooth muscle cell growth. The receptors that mediate the mitogenic effect have been examined. The circulating plasma levels are increased in patients with severe hypertension. These findings indicate that the sympathetic cotransmitter neuropeptide Y may be of importance in sympathetic vascular regulation and involved in pathophysiologic conditions.
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PMID:Neuropeptide Y and hypertension. 874 7


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