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

In normotensive rats, microinjections of neuropeptide Y (2.5 to 25 pmol) into the unilateral nucleus tractus solitarius elicited dose-dependent vasodepressor and bradycardiac responses accompanied by an inhibition of sympathetic nerve firing. After microinjections of the alpha 2-adrenergic receptor antagonist yohimbine (100 ng) into the nucleus tractus solitarius, the depressor and bradycardic responses to the injection of neuropeptide Y (25 pmol) into the nucleus tractus solitarius were significantly attenuated. In contrast, pretreatment with the alpha 1-adrenergic receptor antagonist doxazosin (200 ng) injected into the nucleus tractus solitarius did not alter these responses. In spontaneously hypertensive rats, microinjections of neuropeptide Y (25 pmol) into the nucleus tractus solitarius also elicited depressor and bradycardic responses that were significantly less than those of normotensive Wistar-Kyoto rats. However, pretreatment with yohimbine (100 ng) in the nucleus tractus solitarius did not diminish these depressor responses in spontaneously hypertensive rats. Depressor responses to neuropeptide Y, which was administered after yohimbine pretreatment, were also less in Wistar-Kyoto rats than in spontaneously hypertensive rats. The results suggest that the depressor and bradycardic responses elicited by neuropeptide Y were accompanied by the inhibition of sympathetic nerve activity. These responses may be mediated in part by alpha 2-adrenergic receptor in the nucleus tractus solitarius. The impairment of alpha 2-adrenergic receptor-mediated responses to neuropeptide Y in spontaneously hypertensive rats may contribute to the development of hypertension.
Hypertension 1994 Jan
PMID:Alteration of response to neuropeptide Y in the nucleus tractus solitarius of spontaneously hypertensive rats. 828 83

The presence of three regulatory peptides, corticotropin-releasing hormone, neuropeptide Y and endothelin-1, was studied by radioimmunoassay in the tumor tissue of an ACTH-secreting bronchial carcinoid. A 36-year-old female was admitted to hospital because of moon face, central obesity and hypertension. High levels of plasma ACTH and cortisol and urinary 17-OHCS and 17-KS were found. One mg dexamethasone did not suppress plasma ACTH and cortisol levels, but 8 mg did so slightly. Corticotropin-releasing hormone (100 micrograms, iv) stimulated plasma ACTH levels (0 min; 34.8 pmol/l; 30 min; 41.1 pmol/l). The computerized tomography showed the presence of a tumor in the right lung. This lung tumor was removed surgically and has been shown by microscopical examination to be a bronchial carcinoid with ACTH-positive cells. The tumor tissue concentrations of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 were 3.34 pmol/g wet weight, 8.07 pmol/g wet weight and 0.92 pmol/g wet weight, respectively, although plasma concentrations of these three peptides were not elevated. Reverse phase high performance liquid chromatography showed that immunoreactive peptides in the tumor tissue were mainly eluted in the position of the standard peptides. These findings indicate that this case of ACTH-secreting bronchial carcinoid had high levels of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 in its tumor tissue and suggested that these peptides may act locally, in a paracrine or autocrine manner, in the tumor.
 ...
PMID:An ACTH-secreting bronchial carcinoid: presence of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 in the tumor tissue. 838 6

Muscle nerve sympathetic activity (MSA) was recorded during wakefulness in 11 patients with obstructive sleep apnea (OSA) and in 9 sex- and age-matched healthy control subjects. Plasma levels of norepinephrine (NE) and neuropeptide Y were analyzed. Five patients had established hypertension (resting supine systolic BP/diastolic BP > or = 160/95 mm Hg). The investigation was performed after a minimum of 3 weeks' washout period of antihypertensive medication. Muscle sympathetic activity during supine rest was higher in patients compared with controls (p < 0.01) with no difference between normotensive and hypertensive patients. However, systolic, but not diastolic, BP was positively related to resting MSA (n = 20, p < 0.01). There was no significant correlation between body mass index and MSA. Resting MSA was unrelated to disease severity expressed as apnea frequency or minimum SaO2 during the overnight recording. Both the arterial and venous plasma norepinephrine was higher in patients compared with controls (p < 0.05). Plasma levels of NE correlated to resting MSA (p < 0.01) in the whole study group (patients and controls) but not within the respective subgroups. No significant correlation, however, was found between plasma NE (arterial and venous) and BP. Plasma neuropeptide Y-like immunoreactivity was similar in patients and controls. However, one patient with hypertension had approximately twice this level in repeated samples. It is concluded that neurogenic sympathetic activity as well as circulating plasma NE is increased in patients with OSA. This increased sympathetic activity during awake supine rest may reflect a pathophysiologic adaptation to hypoxia and hemodynamic changes occurring at repetitive apneas during sleep. The correlation between MSA and systolic BP implies that this mechanism may be directly or indirectly involved in the development of cardiovascular complications in OSA.
 ...
PMID:Augmented resting sympathetic activity in awake patients with obstructive sleep apnea. 840 98

The effects of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY1-36) on food intake and pain sensitivity in hot plate test were studied in spontaneously hypertensive rats (SHRs) and in normotensive Wistar-Kyoto (WKy) rats. In satiated SHRs NPY1-36 failed to significantly increase intake at doses that produced a strong effect in satiated WKy rats (0.25-1.25 nmol). Conversely, both NPY1-36 and the C-terminal fragment NPY13-36, a putative selective agonist for the Y2-receptor for NPY, enhanced the spontaneously occurring hypoalgesia of SHRs, having no effect in WKy rats. The present results indicate that the NPY central systems involved in the control of regulatory functions are differently tuned in SHRs and WKy rats, suggesting possible involvement of these systems in the genesis of hypertension.
 ...
PMID:Centrally administered neuropeptide Y fails to increase food intake but enhances hypoalgesia in spontaneously hypertensive rats. 847 94

Neurones containing neuropeptide Y (NPY) may participate in central cardiovascular control by tonically influencing barosensitive neurones within the nucleus tractus solitarius. The present study has employed both in situ hybridisation histochemistry and receptor autoradiography, to visualise the expression of prepro-NPY mRNA in the forebrain and to determine the NPY receptor subtype(s) in the brainstem, respectively. Prepro-NPY gene expression was visualised in the hypothalamus, cortex, dentate gyrus and lateral reticular thalamus from age-matched spontaneously hypertensive rats (SHR) and normotensive Don Ryu rats (DRY) and Wistar Kyoto rats (WKY). Quantitative densitometry revealed an increase in the NPY transcript in the arcuate nucleus of SHR rats compared to their normotensive counterparts. Autoradiography using [125I]Bolton-Hunter-NPY (BH-NPY, 15 pM) demonstrated NPY binding sites in the area postrema, the commissural nucleus tractus solitarius (cNTS) and the inferior olivary complex. NPY (1 microM) and peptide YY (1 microM), but not [Leu31,Pro34]NPY (10-100 nM), fully inhibited the binding of [125I]BH-NPY. These results indicate that NPY receptors of the Y2 subtype predominate in the dorsal vagal complex. Unilateral nodose ganglionectomy resulted in a partial loss of NPY binding sites in the commissural NTS, but not the area postrema, suggesting that a proportion of binding sites (Y2 subtype) are present on central vagal terminals. While all three rat strains appear to have the same relative proportions of NPY receptor subtypes in the brainstem, the relevance of the differential NPY gene expression in the arcuate nucleus regarding central cardiovascular control mechanisms and/or the pathogenesis of hypertension remains to be elucidated.
 ...
PMID:Neuropeptide Y gene expression and receptor autoradiography in hypertensive and normotensive rat brain. 871 61

To comprehend the relationship between the distribution of perivascular neuropeptides and remodified structure of arterioles in hypertension, we applied the technique of sheeting from pia matter of spontaneously hypertensive rats (SHR) to reveal branches at all levels of the vascular network so as to make an overall and stereoscopic observation of the vasculature. In addition, immunohistochemical technique and image analyser were applied to analyse qualitatively and quantitatively neuropeptide Y(NPY)-containing innervation in the vasculature. Findings revealed that the surface density of NPY-containing innervation and integral luminous density of positive reaction particle for anti-NPY in middle cerebral artery and its branches -small arteries and arterioles of SHR were significantly increased as compared with findings in Wistar Kyoto. The results reveal that an increase in density of NPY-containing innervation of cerebral small arteries and arterioles intensifies action of nutritive adjustment of vascular smooth muscle and is clearly related with increase of contractive excitability of artery, hypertrophy of artery, smooth muscle cells and the development of hypertension.
 ...
PMID:[Study on neuropeptide Y-containing innervation of cerebral small arteries and arterioles in spontaneously hypertensive rat]. 873 97

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.
 ...
PMID:Neuropeptide Y and hypertension. 874 7

The 36-amino acid human neuropeptide Y is a vasoactive compound released after stimulation of the sympathetic nervous system. In addition to its direct and long-lasting vasopressor effects, it may potentiate the constrictor action of catecholamines and other vasoconstrictors at doses that do not per se exert vascular effects. Using the hand vein compliance technique, we have previously shown that neuropeptide Y also constricts superficial hand veins and that its effects may last for several hours. In this study, we investigated the local effect of neuropeptide Y on alpha 1-adrenergic venoconstriction in nine healthy volunteers at dose rates that did not affect venous compliance. On separate days, cumulative dose-response curves to phenylephrine alone and with coadministration of 1 or 30 pmol neuropeptide Y per minute were constructed, and the responses were fitted to a four-parameter logistic equation. Neuropeptide Y dose dependently shifted the phenylephrine curves toward lower dose rates without affecting maximal effects. ED50 values for phenylephrine alone and with 1 or 30 pmol/min neuropeptide Y were 4.0, 4.9 (P = NS versus control), and 1.2 (P < .005) nmol/min, respectively. Comparison with neuropeptide Y dose-response curves revealed that the interaction was synergistic. These are the first data in humans to show that small dose rates of neuropeptide Y may potentiate alpha-adrenergic effects in vivo. Because this interaction occurs at estimated local concentrations nearly achieved in humans, these studies suggest that neuropeptide Y might modulate the filling of this capacitance system in vivo.
Hypertension 1996 Sep
PMID:Subconstrictor doses of neuropeptide Y potentiate alpha 1-adrenergic venoconstriction in vivo. 879 37

Defining the roles of the vasoconstrictor peptide neuropeptide Y (NPY) in the cardiovascular system is difficult due to lack of availability of specific NPY receptor antagonists. We report the in vivo NPY receptor blocking actions of a novel nonapeptide dimer, 1229U91 {(IleGluProDprTyrArgLeuArgTyrNH(2)(2)}, and describe its hemodynamic effects. In anesthetized normotensive rats, 1229U91 produced significant and dose-dependent reductions in NPY-reduced hemodynamic responses. 1229U91 (3-30 nmol/kg intravenously, i.v.) attenuated the pressor response (34 +/- 6-84 +/- 1%) and the increases in renal vascular resistance (RVR, 56 +/- 9-94 +/- 2%) produced by NPY (1 nmol/kg i.v.). Intravenous norepinephrine (NE)-induced hemodynamic responses were not altered by 1229U91. 1229U91 also produced dose-dependent inhibition of NPYinduced vasoconstrictor responses in anesthetized dogs and spontaneously hypertensive rats (SHR). These data demonstrate that 1229U91 is a selective NPY receptor antagonist. 1229U91 had no effect on resting hemodynamic variables in these preparations. In conscious SHR, 1229U91 did not produce significant changes in blood pressure (BP) or heart rate (HR) over a wide dose-range (15-1,500 nmol/kg i.v.). Lack of effect of the NPY receptor antagonist in SHR suggests that NPY does not contribute to the maintenance of BP in this hypertension model.
 ...
PMID:Hemodynamic characterization of a novel neuropeptide Y receptor antagonist. 885 42

Since its discovery in 1982, neuropeptide Y (NPY) has been shown to have numerous effects mediated by a growing number of NPY receptors in both the CNS and peripheral nervous system. Perhaps best appreciated is the role of NPY in the control of systemic blood pressure, together with its effects on feeding, anxiety and memory. However, recent evidence increasingly supports an important role for NPY in mediating analgesia and hyperalgesia by distinct central and peripheral mechanisms. In this review we concentrate on this important aspect of NPY pharmacology and consider mechanisms controlling the expression of NPY and its receptors. In addition, we also present the more recent data describing the other possible roles for NPY-NPY agonists and antagonists may be useful in the treatment of conditions as varied as anorexia, epilepsy, anxiety, depression, hypertension and heart failure.
 ...
PMID:The therapeutic potential of neuropeptide Y. Analgesic, anxiolytic and antihypertensive. 887 28


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>