Levels Of NPY-LI Research Articles

Differential effects of clonidine and reserpine treatment on neuropeptide Y content in some sympathetically innervated tissues of the guinea-pig

The effects of treatment with reserpine and/or the selective α 2-adrenoceptor agonists clonidine and oxymetazoline on tissue levels of neuropeptide Y (NPY)-like immunoreactivity (-LI) and noradrenaline (NA) were studied in the guinea-pig. Clonidine treatment was associated with an increase in the levels of NPY-LI in the right atrium in a time- and dose-dependent manner. A significant (45%) elevation of the right atrial content of NPY-LI was present 2 h after administration of clonidine (50 μg kg −1 s.c.). After 24 h of repeated clonidine treatment the atrial levels of NPY-LI had increased by 95%. Following chronic clonidine treatment for two weeks, however, the right atrial NPY levels were similar to those in control animals. The corresponding cell-body content of NPY-LI in the stellate ganglion, remained unaffected by clonidine treatment. The levels of NPY-LI were also increased in the gastrocnemius muscle, spleen and adrenal gland after clonidine treatment while no changes were detected in the vas deferens or hypothalamus. The reserpine-induced reduction of NPY-LI in the right atrium, spleen, gastrocnemius muscle and adrenal gland was markedly inhibited by concomitant clonidine treatment while no effect was observed on NA depletion. The adrenoreceptor antagonists phenotolamine, prazosin and yohimbine all inhibited the increase in cardiac content of NPY-LI seen after clonidine treatment. No elevation of tissue content of NPY-LI was observed after oxymetazoline (50 μg kg −1 s.c.) which, however, reversed the reserpine-induced depletion of NPY-LI. The reserpine-induced increase in content of NPY-LI in the stellate ganglion was also inhibited by clonidine and oxymetazoline. It is concluded that clonidine and oxymetazoline act in opposing directions compared to reserpine on the content of NPY-LI in certain tissues involved in cardiovascular regulation. The mode of action of these α 2-agonists may be related to a centrally reduced sympathetic neuronal activity and an ensuing attenuation of peptide synthesis. Also, an accumulation of peptide in terminal areas due to diminished release via local prejunctional effects could contribute to their effect on NPY levels.

Neuropeptide Y and non-adrenergic sympathetic vascular control of the cat nasal mucosa.

Neuropeptide Y (NPY) coexists with noradrenaline (NA) in a population of perivascular nerves in the cat nasal mucosa. In the present study, NPY was found to exert non-adrenergic nasal vasoconstrictor actions. Postganglionic sympathetic nerve stimulation induced a release of NPY-like immunoreactivity (LI) concomitant with vasoconstriction in the nasal mucosa. About 60 and 70% of the vasoconstrictor responses upon sympathetic stimulation at 2 and 10 Hz, respectively, remained after pretreatment with phenoxybenzamine and propranolol which abolished the effects of exogenous NA. Preganglionic denervation one week prior to the experiments did not change the vasoconstrictor response to sympathetic nerve stimulation or the NA or NPY contents of the nasal mucosa. The levels of NPY-LI in the superior cervical ganglion were however reduced. After reserpine treatment, which depleted the nasal NA content by almost 90% and the NPY content by 50%, a vasoconstrictor response to nerve stimulation was still present. After reserpine treatment combined with preganglionic denervation, nerve stimulation simultaneously induced an increased output of NPY-LI and a marked long-lasting vasoconstriction which was not influenced by phenoxybenzamine and propranolol. The reserpine-induced depletion of NA was not influenced by preganglionic denervation while the reduction in the nasal content of NPY-LI was prevented. In conclusion, NPY could be a non-adrenergic mediator of sympathetic vascular effects in cat nasal mucosa.

Elevations of neuropeptide Y-like immunoreactivity and catecholamines in plasma on increased intracranial pressure in the pig.

Graded increases of intracranial pressure (ICP) in anaesthetized pigs induced elevations of plasma levels of neuropeptide Y (NPY)-like immunoreactivity (LI) and catecholamines, simultaneously with hypertension and tachycardia. Plasma adrenaline (ADR) increased at a lower ICP-level than did the plasma levels of noradrenaline (NA) and NPY-LI. At the maximal ICP elevation, 22.9 kPa (172 mmHg), plasma NPY-LI was increased about 10-fold, from 48 +/- 8 pmol/l in the basal state, while NA and ADR concentrations increased more than 100-fold. At this maximal ICP-level the plasma levels of NPY-LI were correlated to the concentrations of both NA (r = 0.87, P less than 0.01) and ADR (r = 0.92, P less than 0.001). Plasma NPY-LI continued to increase to about 1000 pmol/l, 10 min after the maximal elevation of ICP was discontinued, while the catecholamines then had declined considerably. A slight cardiac release of NPY-LI was observed at the maximal elevation of ICP. The half-life of NPY-LI in plasma was about 6 min upon systemic infusion. At plasma levels similar to those obtained upon maximal ICP elevation, exogenous NPY caused slight vasoconstriction in the spleen and skeletal muscle, but had no effects on coronary blood flow or systemic blood pressure. This suggests that NPY mainly exerts local actions after release from nerve endings, while levels of circulating NPY in plasma must be very high to influence blood flow in some organs. It is concluded that elevation of ICP results in hypertension and tachycardia related to elevated plasma levels of NPY-LI and catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuropeptide Y (NPY) and the pig heart: Release and coronary vasoconstrictor effects

The effects of electrical stimulation of the stellate ganglia on the arterio-venous concentration differences of neuropeptide Y (NPY)-like immunoreactivity (LI) over the pig heart were studied in vivo in relation to changes in heart rate and left ventricular pressure. Furthermore, the effects of NPY on coronary vascular tone were analysed in vivo and in vitro. Stellate ganglion stimulation at a high frequency (10 Hz) caused a clear-cut, long lasting increase in plasma levels of NPY-LI in the coronary sinus compared to the aorta, suggesting release of this peptide from sympathetic terminals within the heart. The stimulation-evoked overflow of NPY-LI from the heart was enhanced about 3-fold by alpha-adrenoceptor blockade using phenoxybenzamine, suggesting that NPY release is under prejunctional inhibitory control by noradrenaline (NA). Combined alpha- and beta-adrenoceptor blockade abolished most of the positive inotropic response of the heart upon stellate ganglion stimulation, while a considerable positive chronotropic effect remained. After guanethidine treatment, stellate ganglion stimulation still produced a small positive inotropic and chronotropic effect on the heart. The stimulation evoked NPY overflow was markedly reduced by guanethidine indicating an origin from sympathetic nerve terminals. Injection of NPY into the constantly perfused left anterior descending artery in vivo caused a long lasting, adrenoceptor antagonist resistant increase in perfusion pressure, suggesting coronary vasoconstriction. NPY contracted coronary arteries in vitro via a nifedipine-sensitive mechanism. NA dilated coronary vessels both in vivo and in vitro via beta-adrenoceptor activation. It is concluded that sympathetic nerve stimulation increases overflow of NPY-LI from the heart suggesting release from cardiac nerves in vivo. The vasoconstrictor effect of NPY on coronary vessels seems to be independent of adrenergic mechanisms and readily antagonized by the calcium antagonist nifedipine.

Co-release of neuropeptide Y and catecholamines upon adrenal activation in the cat.

The release of neuropeptide Y (NPY)-like immunoreactivity (-LI) in relation to catecholamines from the cat adrenal was studied in anaesthetized animals. Abdominal surgery increased plasma levels of NPY-LI from 65 +/- 6 to 149 +/- 26 pmol l-1. A positive veno-arterial concentration gradient over the adrenal gland was found for both NPY-LI, adrenaline (Adr) and noradrenaline (NA) during basal conditions. Asphyxia for 2 min increased the output of both NPY-LI and catecholamines from the adrenal. Electrical stimulation of the splanchnic nerve caused a marked increase in adrenal output of NPY-LI and catecholamines. The adrenal content of NPY-LI, as well as the release of NPY-LI from the adrenal, was at least 1000-fold lower on a molar basis than that of catecholamines. The concentration of NPY-LI in the adrenal vein upon splanchnic nerve stimulation was in the nM range. Reversed-phase HPLC characterization revealed that NPY-LI in the adrenal, and in the adrenal venous plasma collected during splanchnic nerve stimulation, was closely related to synthetic porcine NPY. Stimulation with bursts of 20 Hz for 1 S with 10 s intervals for 2 min caused a four-fold higher output of NPY-LI and Adr compared to a continuous stimulation with 2 Hz, giving the same number of impulses. The NA output, however, was only slightly increased by burst stimulation. Guanethidine did not reduce the adrenal output of NPY-LI or catecholamines induced by splanchnic nerve stimulation, while the release was abolished by chlorisondamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuropeptide Y-like immunoreactivity in adrenaline cells of adrenal medulla and in tumors and plasma of pheochromocytoma patients

The occurrence of neuropeptide Y (NPY)-like immunoreactivity (LI) in the adrenal gland of several species as well as in tumor tissue and plasma from pheochromocytoma patients was investigated. NPY-LI was present in chromaffin cells of the adrenaline type in all species investigated except in the pig, as demonstrated by a colocalization of NPY-LI and the adrenaline-synthetizing enzyme phenylethanolamine N-methyltransferase (PNMT). NPY-LI in the adrenaline cells of the cat was clearly separated from the neurotensin-LI in the noradrenaline dopamine-beta-hydroxylase-positive, PNMT-negative cells. NPY-LI seems to co-exist with enkephalin-like material in the chromaffin cells. In addition, NPY-LI was present in nerves both within the adrenal cortex and medulla. The highest levels of NPY-LI were found in mouse and cat, while only a very low amount of NPY-LI was present in the pig adrenal. Characterization of the adrenal NPY-LI by reversed-phase high-performance liquid chromatography revealed that the main peak was similar to porcine NPY. In addition, two minor peaks of NPY-LI were present. High levels of NPY-LI were found in plasma and tumors from the pheochromocytoma patients. During manipulation of the tumors upon surgical removal, there was a marked increase in plasma NPY-LI in parallel with the raise in catecholamines and in blood pressure. At least two forms of NPY-LI were present in plasma and tumor extracts from pheochromocytoma patients with the main peak corresponding to porcine NPY. Since NPY exerts vasoconstrictor effects, it may be postulated that NPY contributes to the adrenal cardiovascular response and to the hypertension seen in pheochromocytoma patients.

Neuropeptide Y and sympathetic vascular control in man

A parallel increase in systemic plasma levels of neuropeptide Y (NPY)-like immunoreactivity (LI) and noradrenaline (NA) was found during thoracotomy and surgery involving cardiopulmonary bypass in man. Thus, plasma levels of NPY-LI increased from 29 ± 4 pmol/l before anaesthesia to 59 ± 10 after thoracotomy and to 87 ± 8 pmol/l upon cardiopulmonary bypass. The corresponding NA levels increased from 1.3 ± 0.1 nmol/l before anaesthesia to 3.0 ± 0.6 and 4.2 ± 5 nmol/l after thoracotomy and cardiopulmonary bypass, respectively. A significant correlation was found between plasma levels of NPY-LI and NA during the operation but not between NPY-LI and adrenaline. The NPY-LI in human plasma was found to be similar to synthetic porcine NPY on reversed phase high performance liquid chromatography. Human submandibular arteries contained high levels of NPY-LI ( 24 ± 3 pmol/g ). In in vitro experiments on isolated human submandibular arteries, NPY in low concentrations (1000 pmol/l) was found to potentiate the contractile effects of NA or transmural nerve stimulation and to exert vasoconstrictor activity per se in higher concentrations. The calcium-entry antagonist nifedipine abolished both the NPY-induced contractions and the enhancement of NA-evoked contractions. NPY depressed the nerve stimulation-evoked 3H-NA release from human submandibular arteries via a prejunctional mechanism which was resistant to nifedipine. NPY contracted human mesenteric veins and renal arteries, but not mesenteric arteries. In conclusion, NPY seems to be co-released with NA upon sympathetic activation in man. Furthermore, NPY exerts both pre- and postjunctional effects on sympathetic control of human blood vessels.

Differential effects of reserpine and 6-hydroxydopamine on neuropeptide Y (NPY) and noradrenaline in peripheral neurons.

The effects of 6-hydroxydopamine (6-OHDA) and reserpine pretreatment on peripheral neuropeptide Y (NPY)- and noradrenaline (NA)-containing neurons were studied in guinea-pigs. Ten days after 6-OHDA pretreatment, a 60-80% reduction of the NA content was observed in the right atrium of the heart, stellate ganglion and spleen. The content of NPY-like immunoreactivity (LI) was reduced by about 50% in the heart, not changed in the spleen while it increased to 200% of control in the stellate ganglion. Immunohistochemistry showed a pronounced loss of NPY- and tyrosinehydroxylase (TH)-immunoreactive (IR) nerves in the heart but not in the spleen. Increased NPY-IR was seen in axons and cell bodies of the stellate ganglion. Reserpine pretreatment (thereshold dose 0.5 mg X kg-1) caused a dose- and time-dependent reduction of the content of NPY-LI in the heart. A maximal depletion of NPY-LI (about 80%) was observed 5 days after reserpine. Reserpine pretreatment also reduced the content of NPY-LI in the spleen, while no significant change was observed in the adrenal gland or vas deferens. The levels of NPY-LI increased in the stellate ganglion to about 180% of control 5 days after reserpine. Immunohistochemical analysis revealed an almost total loss of NPY-IR nerve fibres in the heart as well as around blood vessels in the lung and skeletal muscle. No detectable changes were observed in perivascular NPY-IR nerves in the spleen, vas deferens or kidney. TH-IR nerves remained unchanged after reserpine, thus indicating that the observed loss of NPY-IR nerves was due to a depletion of NPY and not a degeneration. No change in the levels of substance P-LI was observed in the right atrium 5 days after reserpine. NA was, in contrast to NPY, markedly depleted in all tissues investigated after reserpine treatment. The depletion of NA was more extensive, and occurred more rapidly and at much lower doses as compared to the effects on NPY-LI. Ligations of the sciatic nerve revealed that NPY-LI was transported axonally with a rapid rate (3 mm/h). Reserpine pretreatment significantly increased the amount of accumulated NPY-IR above the ligation, suggesting an increase in axonal transport. High performance liquid chromatography revealed that the NPY-LI consisted of two major peaks in the stellate ganglia, while only one peak closely corresponding to porcine NPY was seen in the right atrium. In conclusion, 6-OHDA pretreatment depletes NPY-LI in certain terminal regions and increases NPY-LI in ganglia.(ABSTRACT TRUNCATED AT 400 WORDS)