Neuropeptide Y (NPY) and sympathetic control of blood flow in oral mucosa and dental pulp in the cat

Neuropeptide Y (NPY) immunoreactivity (-IR) was found to be present in perivascular nerves in the cat dental pulp and oral mucosa. Many ganglion cells in the superior cervical ganglion also contained NPY-IR. Ligation of the inferior alveolar or lingual nerves produced an accumulation of NPY-IR in axons proximal to the site of ligation, suggesting an anterograde axonal transport of the peptide. After unilateral sympathectomy the NPY-IR disappeared in the dental pulp and oral mucosa on the ipsilateral side. Reversed phase high performance liquid chromatography showed that the main peak of NPY-like immunoreactivity found in the superior cervical ganglion co-chromatographed with synthetic porcine NPY. Changes in blood flow in dental pulp or oral mucosa were measured indirectly by recording local clearance of ¹²⁵I during electrical stimulation of the sympathetic nerve or during close intra-arterial infusion of noradrenaline or NPY. All three procedures resulted in a pronounced decrease in local blood flow of a similar magnitude in both tissues. After a-adrenoceptor blockade with phentolamine, the vasoconstrictor effect of noradrenaline was abolished. However, the effect of sympathetic stimulation after phentolamine was only partially reduced (23–54%) and the response to NPY was almost unaffected by the a-receptor blockade. The remaining effect of sympathetic stimulation after phentolamine was abolished by guanethidine. However, the response to NPY was not changed by the latter drug. In conclusion, the vasoconstrictor response in the dental pulp and oral mucosa caused by activation of sympathetic nerves is more resistant to phentolamine than the response induced by infusion of exogenous noradrenaline. Since NPY is probably co-localized with noradrenaline in the sympathetic perivascular nerves and NPY reduces local blood flow,it is proposed that this peptide is involved in sympathetic vascular control in oral tissues.     

Release of neuropeptide Y upon haemorrhagic hypovolaemia in relation to vasoconstrictor effects in the pig

Neuropeptide Y is co-stored with noradrenaline in peripheral sympathetic nerves, but is not present in the adrenal chromaffin cells in the pig. Plasma levels of neuropeptide Y-like immunoreactivity and catecholamines were studied upon haemorrhagic shock in the anaesthetized pig. The animals were bled in two successive steps (30 and 10 ml kg^–), resulting in a reduction of the mean arterial blood pressure by 44% and 53 %, respectively. Plasma levels of noradrenaline increased abruptly after the first bleeding from 1.21 ± 0.27 to 26.5 ± 6.3 nmol 1^-1. Plasma neuropeptide Y showed a progressive increase from 62 ± 8 pmol 1^–1 in the basal state to 365 ± 98 pmol 1^–1 at 60 min after the first bleeding. After the second bleeding plasma neuropeptide Y and noradrenaline showed a largely parallel increase and finally reached levels of 2524 ± 580 pmol 1^–1 and 316 ± 117 nmol 1^–1, respectively. A veno-arterial gradient of neuropeptide Y and noradrenaline indicating local release was present over the spleen after both bleeding steps. The overflow of neuropeptide Y was delayed about 15 min compared to noradrenaline after the initial bleeding. Depletion of the neuropeptide Y content after shock in the heart and skeletal muscle supported local release also from these organs. Infusions of neuropeptide Y to obtain similar plasma concentrations as during shock (nM range) caused reduction in blood flow as determined by the radionuclide-labelled microsphere technique in several organs including spleen and skeletal muscle (threshold response at 319 ± 22 pmol 1^–1) but not in heart and brain. In conclusion, both neuropeptide Y and noradrenaline were markedly elevated in plasma upon haemorrhagic shock, suggesting release from sympathetic nerve terminals. Neuropeptide Y could therefore have a role as a sympathetic neurotransmitter, and during severe stress, circulating plasma levels are in the range where vasoconstriction is evoked by exogenous NPY.     

Time-dependent effects of ischaemia on neuropeptide Y mechanisms in pig renal vascular control in vivo

We have investigated the effects of ischaemia on neuropeptide Y (NPY) mechanisms involved in sympathetic vascular control of the pig kidney in vivo. Reperfusion after 2 h of renal ischaemia was associated with local overflow of noradrenaline (NA) but not of NPY-like immunoreactivity (-LI). Renal sympathetic nerve stimulation 10 min into reperfusion evoked markedly reduced vasoconstrictor effects and significantly less overflow of NA (reduced by 70% from the pre-ischaemic conditions), whereas NPY-LI overflow was unaltered. Renal vasoconstrictor responses to exogenous peptide YY (PYY), phenylephrine and angiotensin II were strongly attenuated after this ischaemic period, while vasoconstriction to α,β-methylene ATP was maintained to a larger extent. The renal vascular responses and NA overflow had become partially normalized within a 2 h recovery period. In contrast, the renal vasoconstrictor response and the overflow of NPY-LI upon sympathetic nerve stimulation were enhanced after 15 min of renal ischaemia. In parallel, the PYY-evoked renal vasoconstriction was selectively and markedly prolonged after the 15 min of ischaemia. In the presence of the NPY Y₁ receptor antagonist BIBP 3226, the augmented vascular response to nerve stimulation was significantly attenuated. We conclude that reperfusion after 2 h of renal ischaemia is associated with local overflow of NA, whereas the sympathetic nerve-evoked release of NA and the reactivity of the renal vasculature to vasoconstrictor stimuli are reversibly reduced. Furthermore, possibly due to an impaired local degradation, the role of neurogenically released NPY in renal sympathetic vasoconstriction is enhanced after short-term (15 min) ischaemia compared with control conditions.     

Neuropeptide Y (NPY) co-exists with tyrosine hydroxylase and potentiates the adrenergic contractile response of vascular smooth muscle in the human uterine artery.

The human uterine artery was studied by immunocytochemistry and in vitro pharmacology. Nerve fibres containing immunoreactivity for neuropeptide Y (NPY) were encountered in the media, adventitia, smooth muscle layers and surrounding the vasa vasorum. Approximately 50% of the nerve fibres containing NPY also stored immunoreactivity for tyrosine hydroxylase (TH) and TH activity was found in no other fibres. Noradrenaline (NA) contracted the isolated uterine artery in a concentration dependent manner. The presence of increasing doses of NPY shifted the concentration-response curve for NA to the left. Consequently the pD2-values were increased indicating a potentiation of the adrenergic effects induced by NPY. The results demonstrate the existence of NPY in adrenergic nerve fibres surrounding the human uterine artery. A close co-operation between NPY and NA in the neuronal control of smooth muscle is suggested.     

Neuropeptide Y innervation of the rodent pineal gland and cerebral blood vessels

Neuropeptide Y (NPY)-immunoreactivity has been shown to be present in sympathetic nerve fibres in the rat pineal gland and a dense network of NPY-containing nerve fibres demonstrated to innervate the rat circle of Willis. The NPY content of the major rabbit intracranial arteries was determined by radioimmunoassay and maximal levels found in the anterior cerebral arteries. After bilateral superior cervical ganglion (SCG) removal, no NPY was detectable in the rat pineal gland; however, significant NPY-immunoreactive nerve fibres remained throughout the rat vertebrobasilar arteries, and 47% of the assayable NPY was still present. Neither intraventricular 6-hydroxydopamine (6-OHDA) nor the combination of 6-OHDA treatment and SCG removal resulted in any further loss of NPY. In conclusion, the NPY innervation of the pineal gland originates exclusively from the peripheral sympathetic nervous system. In contrast the caudal portion of the rat circle of Willis contains NPY fibres which are resistant to sympathectomy.     

Neuropeptide Y (NPY): a vasoconstrictor in the eye,brain and other tissues in the rabbit

The effect of neuropeptide Y (NPY) on uveal vascular resistance was studied in rabbits by direct determination of uveal blood flow from a cannulated vortex vein. Regional blood flows, in the eye, the brain and several other tissues, were measured, with radioactive microspheres, during neuropeptide Y-infusion in rabbits with and without α-adrenoceptor blockade. Intravenous infusion of increasing doses of neuropeptide Y caused a dose-dependent increase in the total uveal vascular resistance. Maximal effect, a 70% increase, was achieved with 120 pmol kg^-1 min^-1. In the microsphere experiments, this dose rate was given i.v. over 10 minutes and blood flow determinations were made before and at 2 and 10 minutes after the start of the infusion. After 2 minutes of neuropeptide Y, there were marked blood flow reductions in the spleen, kidneys, adrenal glands, gastro-intestinal tract, choroid plexus and pineal and pituitary gland. The effect in the eye was small at 2 minutes, but at 10 minutes local blood flows in the choroid and the ciliary body were decreased by 50% and the iridal blood flow by 30%. Retinal blood flow was not affected by neuropeptide Y. At 10 minutes there were also significant blood flow reductions in the brain, tongue, masseter muscle and several glandular tissues. The effects of neuropeptide Y on local blood flow in rabbits that had been subjected to α-adrenoceptor blockade were very similar to the effects in the animals without α-adrenoceptor blockade. The results show that, in the rabbit, neuropeptide Y has marked effects on local blood flows in several tissues, including the eye, and suggest that neuropeptide Y may significantly contribute to the uveal vasoconstriction during sympathetic nerve stimulation.     

不同肿瘤患者leptin与NPY关系的研究

目的：探讨胃癌等肿瘤患者瘦素（leptin）与神经肽Y（neuropeptide,NPY）的相互关系。方法：应用放射免疫分析测定180例不同肿瘤患者血清leptin和血浆NPY水平,并与30例正常人作比较。结果：①leptin水平与对照组（4．18±0．51ng／m1）比较,胃癌、肝癌、食管癌、直、结肠癌和肺癌组均明显增高,并具显著性差异（P〈0．01;P〈0．05;P〈0．01;P〈0．01;P〈0．05）。正常对照组血浆NPY水平为（150．25±20．33）pg／ml,除肝癌组外,其它各恶性肿瘤组血浆NPY水平均较对照组增高显著。②相关分析显示,胃癌、食管癌、直肠癌患者lepdn浓度增高与NPY增高呈明显正相关,其r值分别为0．354、0．30、0．285,P值均〈0．01。胃癌、肝癌、食管癌、直肠癌leptin与TG之间呈明显正相关,其r值分别为0．301、0．268、0．335,P值均〈0．01;leptin与TC、LDL—C、HDL—C之间无相关性。结论：①胃癌等肿瘤患者存在着高leptin和NPY血症;③leptin、NPY在恶性肿瘤食欲及能量调节过程中合成、分泌、与受体结合力的异常在肿瘤恶病质的形成中发挥重要作用。     

Neuropeptide Y-immunoreactive nerves in the uvea of guinea pig and rat

Neuropeptide Y (NPY)-immunoreactivity has been localized to a rich network of fibres in the uvea of guinea pig and rat. In the iris, NPY-immunoreactive nerves were present in iridial smooth muscle and around blood vessels; similarly throughout the choroid a dense network of NPY-immunoreactive fibres was found surrounding the choroidal vascularization. Following sympathectomy a marked decrease of NPY-immunoreactivity, in particular in the iris and less marked in the choroid, was noted, indicating that these fibres may originate at least in part from neuronal cell bodies in the superior cervical ganglion. The close relationship of the NPY-immunoreactive fibres to blood vessels in both anterior and posterior uvea is consistent with the established vasoconstrictor action of this peptide.     

Sympathetic vascular control of the pig nasal mucosa (III): co-release of noradrenaline and neuropeptide Y

The overflows of noradrenaline (NA) and neuropeptide Y like immunoreactivity (NPYLI) and vascular responses upon sympathetic nerve stimulation were analysed in the nasal mucosa of pentobarbital anaesthetized pigs. In controls, a frequency-dependent increase in NA overflow was observed whereas detectable release of NPY-LI occurred only at 6.9 Hz. Parallel decreases in blood flow in the sphenopalatine artery and vein and in nasal mucosa volume (reflecting blood volume in the venous sinusoids) were observed. The laser Doppler flowmeter signal (reflecting superficial blood flow) increased upon low and decreased upon high frequency stimulation. Twenty-four hours after reserpine pretreatment and preganglionic decentralization, the NA overflow was abolished while a frequency-dependent release of NPY-LI occurred. Forty, 60 and 80% of the vasoconstrictor responses then remained upon stimulation with a single impulse, 0.59 and 6.9 Hz, respectively. Both the vasoconstriction and NPY-LI overflow, however, were subjected to fatigue upon repeated stimulation. In reserpinized animals release of NPY-LI and vasoconstrictor responses were larger upon stimulation with irregular bursts at 0.59 Hz compared to effects seen at stimulation with continuous impulses. Pre-treatment with the a-adrenoceptor antagonist phenoxybenzamine or the monoamine reuptake inhibitor, desipramine, enhanced NA overflow by 2–3 and 1.5 times at 0.59 and 6.9 Hz, respectively. Phenoxybenzamine significantly reduced the nerve-evoked vascular responses while the release of NPY-LI at 6.9 Hz was increased. Desipramine increased the functional responses but reduced the NPY-LI overflow. During tachyphylaxis to the vasoconstrictor effects of the stable adenosine 5′-triphosphate (ATP) analogue α-β-methylene ATP (mATP) in controls, the vasoconstrictor responses as well as the NA and NPY-LI overflow to nerve stimulation were unmodified. In reserpinized animals, however, the vascular responses and the overflow of NPY-LI were reduced after mATP tachyphylaxis. These data show that both NA and NPY are released upon sympathetic nerve stimulation in the nasal mucosa in vivo and this release seems to be regulated via prejunctional a-adrenoceptors. The lack of effect of mATP tachyphylaxis under control conditions makes it less likely that ATP serves as a major mediator of the large nonadrenergic vasoconstrictor component.     

新生儿缺氧缺血性脑病血浆SOD、NPY测定的临床意义

目的 :探讨新生儿缺氧缺血性脑病 (HIE)患者血浆超氧化物歧化酶 (SOD)、神经肽Y(NPY)在各临床分度中的含量及其在疾病中的临床意义。方法 :应用放射免疫分析 (RIA)测定 6 3例HIE患儿血浆SOD、NPY进行综合检测和相关性研究。结果 :SOD、NPY放免测定结果在HIE各临床分度中含量各异 ,与正常对照组均存在明显差异 (p值均 <0 0 5或 <0 0 1)。结论 :HIE患儿血浆SOD、NPY含量与疾病临床分度呈正相关 ,与疾病危重程度、发生发展、预后有关。     

高血压病患者血浆神经肽Y的释放特点及其与血脂代谢的关系

应用放射免疫法测定５０例不同期高血压病患者血浆神经肽Ｙ（ＮＰＹ）释放变化特点并比较其与吸烟、血脂代谢之间的关系。结果发现：高血压病患者血浆ＮＰＹ含量为１４０．３±７３．８ｐｇ／ｍｌ,与对照组比较（７１．１±２１．８ｐｇ／ｍｌ）有显著性差异（Ｐ＜０．０１）;Ⅲ期高血压病患者血浆ＮＰＹ含量明显高于Ⅰ、Ⅱ期高血压病患者（Ｐ＜０．０１）;既往有吸烟史或血糖（ＢＧ）、血甘油三酯（ＴＧ）异常的高血压病患者血浆ＮＰＹ含量较无吸烟史及ＢＧ、ＴＧ正常者明显增高（Ｐ＜０．０１）。提示：高血压病患者血浆ＮＰＹ水平明显升高,而它的升高与吸烟、血甘油三酯及血糖增高有一定关系,它们的共同作用进一步使动脉血管弹性减退,导致微循环障碍,参予了高血压病、冠心病的发病机制与病理生理过程。     

不同肾脏疾病时leptin与NPY的水平变化

目的：探讨不同肾脏疾病时血浆瘦素（leptin）和神经肽Y（NPY）的水平变化及意义。方法：应用放射免疫分析对176例不同肾脏疾病患者血清leptin及血浆NPY水平进行检测,并与35例正常人进行对比。结果：与对照组比较,糖尿病肾病、慢性肾功能不全及血液透析前后血清leptin水平均增高显著（P〈0．05;P〈0．01;P〈0．01）。血浆NPY水平在慢性肾功能衰竭和血液透析前后显著增高（P〈0．01;P〈0．01）。其他各组与对照组比较均无显著性差异（P〉0．05）。与血透前比较,血透后leptin和NPY水平明显降低有显著性差异（P〈0．05;P〈0．05）。相关性分析显示,慢性肾功能衰竭组和血液透析组leptin与NPY之间均呈正相关（r=0．68。t=3．62,P〈0．01;r=0．58,t=4．02,P〈0．01）,其他各组间无相关性。结论：慢性肾脏疾病和慢性肾功能衰竭患者存在高leptin、NPY血症;血液透析过程能增加leptin和NPY的清除率,改善患者的营养状态。     

Action and localization of neuropeptide Y in the human fallopian tube

Using indirect immunohistochemistry, neuropeptide Y-like immunoreactivity was found in nerve fibers around blood vessels and in the muscle layers of the human fallopian tube. Apart from a network of immunoreactive nerve fibers in connection with the luminary epithelium of the isthmus, the distribution resembled that of adrenergic, tyroxine hydroxylase immunoreactive, nerve fibers. Neuropeptide Y was found to have a dose-dependent inhibitory action on the adrenergic contractile response to field stimulation in the external longitudinal muscle layer of the isthmus. Furthermore, neuropeptide Y inhibited [3H]noradrenaline release from isthmic preparations during field stimulation, suggesting a prejunctional inhibitory action on adrenergic neurotransmission.     

Role of nitric oxide in local blood flow control in the anaesthetized dog

Intravenous infusion of N ^G-nitro-L-arginine methyl ester (L-NAME), a potent inhibitor of nitric oxide (NO) formation from L-arginine, provokes marked rises in arterial blood pressure by increasing peripheral resistance. In order to further evaluate the contribution of basal NO-formation to control of organ blood flow, regional blood flow distribution within the myocardium, kidney and brain areas was assessed using the tracermicrosphere technique in anaesthetized dogs. After L-NAME (20 mg kg^–1 i.v.) kidney perfusion was homogeneously reduced by 55% in the entire cortex and the outer medulla. Within the left ventricular myocardium regional blood flow significantly decreased only in sub epicardial layers (–12%), whereas within the entire right ventricle regional blood flow was reduced by 19–24%. A close inverse relationship was found between all changes in regional myocardial blood flows observed after L-NAME and the respective control values. No significant changes in regional blood flow in different areas of the brain were detectable after L-NAME. It is concluded that the contribution of basal NO formation varies greatly between different organs and exhibits significant regional differences within the heart. It is possible that local metabolic mechanisms may compensate functionally for the inhibition of NO synthesis.     

Effects of bilateral carotid occlusion and auditory stimulation on renal blood flow and sympathetic nerve activity in the conscious dog

In conscious foxhounds with intact aortic baroreceptors the effects of common carotid occlusion (C. C. O.; 3 dogs) or excitement (elicited by a sudden loud noise due to firing a pistol; 7 dogs) on renal blood flow (R.B.F.) were studied. C.C.O. increased arterial blood pressure by 40–50 mm Hg and heart rate by 22 beats/min while R.B.F. remained unchanged. When kidney perfusion pressure was maintained during C.C.O. there was also no change in R.B.F. Excitement increased mean aortic blood pressure by 35 mm Hg and heart rate by 84 beats/min; R.B.F. was transiently reduced by 40% of control.In another 3 foxhounds successful recordings of renal sympathetic nerve activity (R.S.N.A.) were obtained in the conscious state for 2–7 postoperative days. The effects of C.C.O. or excitement — elicited by whistling or hand-clapping — on R.S.N.A. were tested. There was pulse-synchronous nerve activity in the resting conscious animal. C.C.O. induced a steady state increase of averaged R.S.N.A. by 62% of control. Excitement was associated with transient bursts of activation of averaged R.S.N.A. by 500% of control.It is concluded that total R.B.F. is not changed during the baroreceptor short-term adjustment of blood pressure although changes in sympathetic outflow to the kidney are observed under comparable conditions. In contrast, excitement causes a much higher degree of sympathetic activation; this is probably responsible for the intense, transient renal vasoconstriction.This study was supported by the German Research Foundation within the S.F.B. 90 Heidelberg     

高血压鼠脑底动脉神经肽Y能神经与颈上神经节、星状神经节的关系

目的　探讨高血压鼠脑底动脉神经肽Y能神经与颈上神经节、星状神经节的关系。方法　应用神经节切除术和免疫组织化学ABC法 ,对 16只自发性高血压鼠脑底动脉神经肽Y能神经纤维的分布进行了观察。结果　对照组自发性高血压鼠大脑前动脉、大脑中动脉、大脑后动脉和基底动脉壁上均可见神经肽Y能阳性纤维 ,纤维似曲线状 ,多呈网状走行 ,密度较高。手术Ⅰ组作双侧颈上神经节切除术 ,脑底主要动脉的阳性纤维明显减少 ;手术Ⅱ组作双侧星状神经节切除 ,脑底主要动脉壁上的阳性纤维明显减少 ;手术Ⅲ组作双侧颈上神经节和星状神经节切除术 ,脑底主要动脉的阳性纤维完全消失。结论　自发性高血压鼠脑底主要动脉的神经肽Y能神经纤维起源于双侧颈上神经节和双侧星状神经节 ,神经肽Y能神经可能在高血压发病中起作用     

Renal blood flow distribution at varying perfusion pressure in the alloperfused dog kidney

Tissue blood flow (TBF), its percent distribution and glomerular blood flow (GBF) were measured using labelled microspheres 15 m in diameter (M) and chicken red blood cells (CRBC) at perfusion pressures (PP) of 17.3, 12.8 and 8.0 kPa (130, 95 and 60 mm Hg) in isolated alloperfused dog kidneys. Renal blood flow (RBF) was never interrupted during the isolation. Experiments with M showed a marked inequality of the tissue blood flow in different parts of the renal cortex at a constant PP of 17.3 kPa. TBF was highest in the outermost quarter and lowest in the juxtamedullary one. Using CRBC, a homogeneous TBF was observed in the outer 3/4 of the renal cortex with a lower flow in the innermost quarter. With M, a typical percent redistribution of TBF and GBF into the inner cortical regions was indicated during PP reduction. With CRBC, this phenomenon was observed only at PP below the range of RBF autoregulation (8.0 kPa) and was much less conspicuous than with M. The smaller size and higher elasticity of CRBC as compared with M, may result in a more realistic reflection of cortical blood flow distribution. The GBF of outermost superficial glomeruli decreases, even with CRBC, with each PP reduction, the difference exhibiting only a 5% significance level. The lower limit of BF autoregulation in these glomeruli seems to be some-what higher than that of total RBF autoregulation.