Selective changes in the <i>α</i>-adrenoceptor-mediated contraction in the senescent rat urinary bladder

The urinary bladder is innervated and functionally regulated by the autonomic nervous system. In order to elucidate the mechanism of functional changes in aged rat urinary bladder, we studied the influence of senescence on, 1) the α-adrenergic contractile response to phenylephrine in the urinary bladder body and trigone, 2) the muscarinic contractile response to carbachol in the body and trigone. The binding characteristics of [3H]quinuclidinyl benzilate (QNB) to muscarinic cholinoceptors were compared in young and aged bladder. Bladders from young (2 - 3 month-old) and aged (27 month-old) male Fischer 344 rats were isolated, cut into strips and mounted in the organ bath, then the developed tension was recorded. Histologically, the aged bladder did not show pathologic changes such as inflammation and hypertrophy. Carbachol-induced contraction in aged rat bladder was identical to that obtained in young rat. In the receptor binding assay, [3H]QNB maximal binding capacity and Kd value were not significantly changed in aged bladder. In contrast, a selective α-adrenergic agonist phenylephrine, elicited greater contractions both in the aged body and trigone than those in young rats. The augmentation of α-adrenoceptor-mediated contractions in aged bladder may induce urinary dysfunction such as voiding difficulty.

3D-QSAR Analysis of DDPH Derivatives for α_1-Adrenoceptor Antagonist Activity

Aim and methods The study of three-dimensional quantitative structure-activity relationship （3D-QSAR） of DDPH and its derivatives has been performed using Apex-3D programme. Results The result indicates that substituents of para- and ortho-positions in phenyl ring of aryloxyalkylamine greatly influence the bioactivity. Conclusion The biophore model and 3D-QSAR equation help us not only further understand receptor-ligand interactions, but also design new compounds with better bioactivity.

Effect of Fish Oil on (-Adrenoceptors and the Activity of Adenylate Cyclase on Myocardial Membrane in Rats

Effects of fish oil on β-adrenoceptors as well as the activity of adenylate cyclase (AC) on rat myocardial membrane were investigated.Supplementation with fish oil had no significant effect on basal activity of AC on myocardial membrane whereas it could markedly inhibit the AC activity stimulated by isoproterenol (ISO). Radioligand binding assays showed that supplementation with fish oil had no effect on Bmax and Kd, compared with saline control. However, supplementation with sheep oil could markedly reduce both the Kd and Bmax, compared with saline control. And the Kd of sheep oil group was greatly decreased than that of fish oil group. The results suggested that supplementation with fish oil mainly affected the activation of AC, not β-adrenoceptor itself.

Mechanism of Anti-β-adrenoceptor Antibody Mediated Myocardial Damage in Dilated Cardiomyopathy

Antibodies against &-adrenoceptor can be detected in serum of patients with dilated cardiomyopathy (DCM), which have 5-agonist-like activity, and induce a positive chronotropic effect on cardiac myocytes by its persistence at full strength. Effects of the antibodies against Padrenoceptor from sera of patients with DCM on myocardial cytotoxicity and cytoplasmic free Ca2+-concentration (LCa2+ji) were observed in the cultured single layer SD rat ventricular cells by using the cytotoxicity assay and fluorescent Ca2+- indicat0r fura-2/AM. The positive sera of the anti-&adrenoceptor antibodies from patients with DCM markedly enhanced myocardial [Ca2+]i. Betaloc, a 5, -receptor blocker, might inhibit the increase of the antibody-mediated myocardial [Ca2+]i, and the sera from healthy donors had no effect on myocardial [Ca2+]i,. Our results suggest that the anti-β-adrenoceptor antibody might increase myocardial [Ca2+]i, and result in myocardial damage. The antibodies might activate receptor-gating Ca2+-channel, thereby causing myocardial [Ca2+]i, rise and calcium overload. Early use of betaloc is recommended in the treatment of dilated cardiomyopathy.

Constructing Biophore of Uroselective α1-Adrenoceptor antagonist

Aim The biophore of uroselective α_1-adrenoceptor antagonist was studied byusing Apex-3D software on an 02 Silicon Graphics Computer Station. Methods Five known antagonists(Indoramin, GG-818, RS100975, R-YM12167, and KMD-3213), which possess both good selectivity and highaffinities to prostate and α_1-AR subtype, were chosen for building the biophore. Using anautomatic filtering software for obtaining reasonable biophores, the filter parameters wereselected: P (probability) > 0.8, active (number of active compounds) ≥ 4, and size (descriptorcenter) ≥ 3. Results Three biophores conformed to the requirements, each of whom contained a basiccenter, an aromatic ring center and H-site according to the structure-activity relationships ofknown α_1-adrenoceptor antagonist. Conclusion The biophore model developed by computer simulationwith Apex-3D software can be used to design and synthesize a new α_1-adrenoceptor antagonist withhigh activity and low side effect.

β_2-adrenoceptor in obstructive airway diseases:Agonism, antagonism or both?

Obstructive airway disease is a complex disease entity including several maladies characterized by bronchoconstriction and abnormal airway inflammation. Reversing bronchoconstriction leads to symptomatic relief and improvement in quality of life, both in reversible(bronchial asthma) and partially reversible(chronic obstructive airway disease) obstructive airway diseases. β2-adrenoceptor expressed in human airway is the main β-receptor subtype, and its activation in airway smooth muscle cells leads to bronchodilatation. Drugs targeting β-adrenoceptors have been around for many years, for which agonists of the receptors are used in bronchodilation while antagonists are used in cardiovascular diseases. This review article summarizes the effect and usage of β2-agonist in obstructive airway disease, addressing the benefits and potential risks of β2-agonist. The article also looks at the safety of β-blocker usage for cardiovascular disease in patients with obstructive airway disease. There is also emerging evidence that non-selective β-blockers with inverse agonism ironically can have longterm beneficial effects in obstructive airway disease that is beyond cardiovascular protection. Further trials are urgently needed in this area as it might lead to a dramatic turnaround in clinical practice for obstructive airway diseases as has already been seen in the usage of β-blockers for heart failure.

Effect of β blockers on β_3-adrenoceptor mRNA Expression in the Rats with Chronic Heart Failure

Objectives To investigate the changes of β3-adrenoceptor (β3-AR) mRNA expression in the rats with chronic heart failure (CHF), and to explore the effect of β blockers (βBs) on β3 mRNA expression. Methods Thirty-four rats were randomly divided into Sham group (n = 10) and heart failure group (n = 24). Rat model was established by aortic constriction. The survival rats in heart failure group were divided into heart failure control group (HF group, n = 6), metoprolol group (MET group, n = 8) and carvedilol group (CAR group, n = 8) three months after operation. Metoprolol tartarte was started orally with 12 mg·kg-1·d-1, carvedilol with 6 mg·kg-1·d-1, isometric saline was started in HF group. After three months of drug therapy, measurement of hemodynamics, index of ventricular mass, the level of β3-AR mRNA expression were performed. Results Compared with Sham group, left ventricular end systolic pressure (LVESP), and the absolute values of maximal rate of rise and fall ( ± dp/dtmax) of left ventricular pressure were all significantly decreased (P < 0.01), left ventricular end diastolic pressure (LVEDP) was significantly increased in HF group (P < 0.01). The hemodynamic parameters were improved by βBs, and carvedilol was more effective than metoprolol (P < 0.01). The index of ventricular mass was higher in HF group than MET group, CAR group and Sham group (P < 0.01). βBs significantly decreased the index of left ventricular mass (LVMI), and Carvedilol was more effective than metoprolol (P < 0.01). The index of right ventricular mass (RVMI) did not change in MET group (P > 0.05), but significant decrease could be seen in CAR group (P < 0.01). The level of β3-AR expression in left ventricle was greater than that in right ventricle whether in the failing heart or in the non-failing heart. Compared with Sham group, the level of β3-AR mRNA expression was significantly increased in HF group (P < 0.01). The levels of β3-AR mRNA expression showed a remarkable decrease in CAR group(P < 0.01), but was not seen in MET group. Conclusions The β3-AR expression level remarkably increases in the rat’s left and right failing ventricles. Carvedilol is more effective on improving hemodynamics and attenuating ventricular remodeling than metoprolol in the rats with CHF. Carvedilol rather than metoprolol downregulates β3-AR expression in the rat’s failing ventricles. The beneficial effect of carvedilol in CHF maybe partly due to the downregulation of β3-AR expression in the failing heart.

Design and Synthesis of Novel Aryloxyalkyl-arylpiperazine Derivatives as α_(1A)-Adrenoceptor Antagonists

A series of 1-[2-(substituted phenoxy)ethyl]-4-(2-methoxyphenyl)-piperazine deriva- tives have been synthesized. The radioligand receptor binding assay indicated that most of them bind with α1-adrenoceptor specifically, and one of the compound possessed subtype A selectivity.

CARDIAC RISK STRATIFICATION IN PATIENTS WITH CONGESTIVE HEART FAILURE:A CATECHOLAMINES-β-ADRENOCEPTOR-cAMP PATHWAY

Objective To investigate the stratification risk of catecholamines-β-adrenoceptor (β-AR)-cAMP pathway for cardiogenic death events in patients with congestive heart failure (CHF). Methods A total of 83 identified CHF patients with a baseline and follow-up plasma levels of norepinephrine (NE) and epinephrine (E), lymphocytes β-AR density (Bmax), and intralymphocyte cAMP content in peripheral blood were followed up. Major cardiogenic death events were registered. Results The period between the initial entry and the last follow-up measurement were 51±16 months, the total duration of clinical follow-up after the last measurement were 14±8 months. During follow-up, 39 patients died of cardiogenic (sudden death 17 patients, worsening heart failure 22 patients). Persistence of high NE, E, and cAMP from baseline to follow-up were confirmed as risk predicting factors of cardiovascular events. Persistence NE above 4.0 nmol/L, E above 3.5 nmol/L, and the intralymphocyte cAMP content above 3.5 pmd·mg-1·pro-1 from baseline to follow-up were significant adverse prognostic predictors. The major cardiogenic death events rates per 100 patients-years were 1.33 and 4.82 in patients with NE below and above 4.0 nmol/L (HR: 2.91; 95% CI: 1.08-7.33; P = 0.015); were 1.42 and 4.36 in the patients with E levels below and above 3.5 nmol/L (HR: 2.64; 95% CI: 1.02-6.41; P = 0.019); were 1.81 and 4.67 in the patients with the intralymphocyte cAMP content below and above 3.5 pmd·mg-1·pro-1 (HR: 2.79; 95% CI: 1.04-6.83; P = 0.017), but difference was not significant between the β-AR density below and above median. Conclusions Persistent increase in circulating catecholamines and intralymphocyte cAMP content may increase the long-term mortality in CHF patients.

Primary study on correlation betweenβ_2-adrenoceptor haplotypes and asthma in children of Han nationality in Chongqing

Objective:To investigatethecorrelationbetweenβ 2 -adrenergicreceptors(β 2 -AR)haplotypesandasthmaof Hannationalitychildrenin Chongqingregion.Methods:PCRandrestrictionfragmentanalysiswereusedto study16,27lociof theβ 2 -ARpolymorphismin76unrelatedasthmaticchildrenandin100healthychildrenandadultsof Hannationali-ty as control.A statisticalanalysisof thecorrelationbetweenglycine(Gly)16allele,Gly16/glutamine(Gln)27haplotype andasthmaticclinicalstatuswas carriedout.Results:Therewas no significantincreaseof thefrequencyof Gly16and Gln27alleleintheasthmaticgroupas comparedwiththecontrolgroup(P>0.05).Therewasa significantincreaseof the frequencyof Gly16alleleandGly16/Gln27haplotypein severeasthmaticcasesthanin themildandmoderateasthmatic ones(P<0.01,0.05).Conclusion:Itis consideredthatasthmais notcausedby GlyandGlnallelesofβ 2 -ARpolymor-phisms.Gly16alleleandGly16/Gln27haplotypearepossiblycorrelatedwiththeseverityof theclinicalmanifestationsin thechildrenof HannationalityinChongqing.

Co-Localization of Alpha1-Adrenoceptors and GPR55: A Novel Prostate Cancer Paradigm?

α1-adrenoceptors (α1-ARs) and “cannabinoid-like” G Protein Coupled Receptor 55 (GPR55) belong to the G-protein coupled receptor (GPCR) family and play a crucial role in regulating prostate function. Although physical and functional interactions between the cannabinoid and adrenergic systems have been reported, analysis of functional interactions between α1-AR and GPR55 in normal and neoplastic prostate has not been reported. Since GPR55 levels are high in rodent adrenal gland, we propose a function link between the adrenergic system and GPR55 receptor. Confocal Laser Scanning Microscopy (CLSM) was employed to examine the endogenous α1-AR and GPR55 expression and their co-localization, expressed as fluorescence, in vitro in human andro-gen-insensitive PC-3 and androgen-sensitive LNCaP prostatic carcinoma cell lines, using the fluo-rescent ligands—Syto 62 (nuclear stain), BODIPY FL-Prazosin (QAPB;fluorescent quinazoline α1-AR ligand) and Tocriflour (T1117;a novel fluorescent diarylpyrazole cannabinoid/GPR55 ligand). Fluorescent ligand binding in untreated PC-3 cells and LNCaP cells and spheroids showed hetero-geneous expression of both α1-ARs and GPR55. A small proportion of cells had both α1-ARs and GPR55 in relatively equal numbers indicating a degree of co-localization. Co-localization of fluo-rescent ligand binding exhibited a stronger correlation in LNCaP (0.87) as compared to PC-3 (0.63) cells. Upregulation of α1-AR was observed in PC-3 cells following chronic doxazosin incubation. Robust T1117 binding, suggestive of GPR55 upregulation, was also observed in these cells. The presence of subtype-rich cells with a degree of co-localization between α1-ARs and GPR55 indicates a possibility for dimerisation or functional interaction and a new paradigm for functional synergism in which interactions may be either between cells or involve converging intracellular signaling processes.

Evidence for a Non-<i>β</i>₂-Adrenoceptor Binding Site in Human Lung Tissue for a Subset of <i>β</i>₂-Adrenoceptor Agonists

The aim of this study was to compare the binding profile of a range of β2-adrenoceptor (β2-AR) agonists and antagonists in human lung tissue. Radioligand saturation and competition binding experiments were performed by filtration with a β2-AR antagonist ([3H]propranolol) or agonist ([3H]vilanterol) radioligand and membrane fragments generated from lung parenchyma in the presence of 100 μM guanosine 5’-[β,γ-imido]triphosphate (Gpp(NH)p). In membranes prepared from human lung parenchyma, carmoterol, formoterol, ICI118551, propranolol and salbutamol resulted in inhibition of [3H]vilanterol binding to levels that were significantly different from indacaterol, salmeterol and vilanterol (ANOVA, Bonferroni post-test, P < 0.001 except formoterol vs indacaterol where P < 0.01). Indacaterol and salmeterol resulted in inhibition of [3H]vilanterol binding to levels that were not significantly different from vilanterol (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol resulted in full inhibition of [3H]propranolol binding to levels not significantly different from ICI118551 (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol bind to an additional site in human lung parenchyma membranes that is distinct from the β2-AR.

Onset Time Profiles for Syncope Associated with <i>α</i>₁-Adrenoceptor Blockers in Males: Analysis of a Spontaneous Adverse Drug Event Database

Background: α1-Adrenoceptor blockers (α1Bs) are used for the treatment of benign prostatic hyperplasia and hypertension, but they are known to cause hypotension-related adverse events. The objective of the present study was to evaluate the onset time profiles for syncope associated with the use of α1Bs. Methods: We analyzed the data obtained from?the Japanese Adverse Drug Event Report (JADER) database for a period from April 2004 until November 2016 and calculated reporting odds ratios (RORs) for eight α1Bs available on the Japanese market, using disproportionality analysis. Moreover, time information recorded in the JADER database was analyzed to evaluate the onset times of adverse events. Results: In total, 186,724 reports for males older than 20 years were analyzed. Significant RORs for syncope, with 95% confidence intervals, were obtained for naftopidil (2.53, 1.81 - 3.53), silodosin (4.24, 2.37 - 5.20), and tamsulosin (2.22, 1.75 - 2.81). The median onset times of syncope for naftopidil, silodosin, and tamsulosin were 37, 26, and 108 days, respectively. The shape parameters obtained by fitting the data for the three α1Bs to the Weibull distribution were all less than 1.0, indicating that all these drugs could be classified as the early failure type. The cumulative incidence rates showed that the onset times of syncope tended to be similar among the three α1Bs. Conclusions: Patients treated with selective α1Bs should be closely monitored for 100 days, especially in the first 20 to 40 days after initiation of silodosin or naftopidil. This information may be useful for patients and healthcare professionals in preventing syncope due to the use of selective α1Bs.

The Expression of β3-adrenoceptor of Left Ventricle and the Effect on Heart Function by Stimulating β3-AR in Rats With Experimental Heart Failure

Objectives To observe the expression of β3-adrenoceptor （β3-AR） of left ventricle and the effect on heart function by stimulating β3-AR in rats with experimental heart failure. Methods Rats were randomly divided into heart failure group and control group. Heart failure models were built up by ligating coronary artery in rats. The expression of β3-AR mRNA were detected with RT-PCR; The change of heart function were observed after administration of BRL37344 （β3-AR agonist） by measuring left ventricular end-systolic pressure （LVESP）, left ventricular end-diastolic pressure （LVEDP）, the maximum pressure ascending rate of left ventricle （＋dp/ dtmax） and the maximum pressure descending rate of left ventricle（-dp/dtmax）. Results The expression of β3-AR mRNA （β3/β-actin） was 0.028±0.005 and the proportion of β3-AR （β3/β1＋β2＋β3） was 5.4%±0.06% in failure rats while the expression of β3-AR mRNA was 0.011 ±0.004 and the proportion was 1.2%±0.04% in control rats; The descending percentage of LVESP, ＋ dp/dtmax and -dp/dtmax were 16.1%, 21.7% and 13.2% respectively with administration of BRL37344 in failure rats, while 12.2%, 15.8% and 11.5% in control rats. Conclusions Compared with control group the expression of β3-AR mRNA of left ventricle was obviously increased and the negative inotropic function with exciting β3-AR was obviously enhanced in failure groups.

Clonidine Inhibits Phenylephrine-Induced Contraction of Rat Thoracic Aortae by Competitive Antagonism of α₁-Adrenoceptors Independent of α₂-Adrenoceptor Stimulation

Clonidine is a classically categorized α2-adrenoceptor (α2-AR) agonist that produces vascular contractions by stimulating arterial smooth muscle α2-ARs. However, clonidine inhibits α1-AR-mediated arterial contractions. Recently, it was suggested that repeated stimulation with clonidine induces desensitization of α2-ARs, thus inhibiting noradrenaline-induced smooth muscle contractions. In the present study, we examined whether clonidine-mediated inhibition of α1-AR contractions involves interactions with α2-ARs in rat thoracic aortae. 1) Clonidine and guanfacine inhibited electrical field stimulation-induced contractions in a concentration-dependent, yohimbine-sensitive manner in isolated rat vas deferens preparations. 2) Clonidine almost completely suppressed phenylephrine-induced sustained contractions of rat thoracic aortae. 3) Clonidine competitively inhibited phenylephrine-induced contractions with a pA2 value of 6.77 at concentrations between 10-7 and 10-6 M. At 10-5 M, clonidine inhibited phenylephrine-induced contractions and dramatically reduced maximum contractions. 4) In contrast, clonidine did not inhibit contractions produced by high KCl or prostaglandin F2α. 5) Inhibition of phenylephrine-induced sustained contractions by clonidine was also produced in the presence of yohimbine. However, guanfacine did not inhibit phenylephrine-induced sustained contractions. These findings suggest that clonidine inhibits phenylephrine-induced contraction of rat thoracic aortae by competitive antagonism of α1-ARs, which is mediated through a mechanism independent of α2-AR stimulation.

Effect of β_3-adrenoceptors on Ventricle Fibrillation Threshold and Effective Refractory Period in Rats With Heart Failure

Objectives To observe the effect of β3-Adrenoceptor （AR） on ventricle fibrillation threshold （VFT） and effective refractory period （ERP） in rats with heart failure. Methods Rats were randomized into control group and heart failure group. The expression of β3-ARmRNA was detected with RTPCR; The VFT, ERP, LVESP,LVEDP, ＋dp/dtmax and -dp/dtmax was measured at the same time with administration of BRL37344 （ 2 nmol / kg, β3- AR agonist）. Results ①Both the expression of β3-AR mRNA and the proportion increased in rats with heart failure in comparison with control rats （0.028 vs. 0.011 and 5.4% vs 1.2%, P 〈 0.05）;② ERP was longer in rats with heart failure than control group （70.5±5.5 ms vs 59.5±6.4ms, P 〈 0.05） and there was no difference of ERP in rats with heart failure with administration of BRL37344 （73.0±4.8 ms vs 70.5± 5.5 ms, P 〉0.05）; ③VFT was lower in rats with heart failure than control group（10.9±0.8 mv vs 30.5± 1.3 mv, P〈 0.05） and decreased obviously in rats with heart failure with administration of BRL37344 （7.1±0.6 mv vs 10.9±0.8 mv, P 〈 0.05） ; The decrease of VFT correlated with the effect on LVESP, ＋dp/ dtmax,-dp/dtmax of BRL37344 and the expression of β3-AR mRNA （correlation coefficient： 0.788, 0.708, 0.759, 0.787; P 〈 0.05）. Conclusions The expression of β3-AR mRNA of left ventricle was obviously increased in rats with heart failure, and activation of β3-AR had no effect on ERP but could decreased VFT which correlated with the effect of β3-AR on LVESP, ＋dp/dtmax, -dp/dtmax and the expression of β3-AR mRNA.

Alpha2-adrenergic receptor activation reinstates motor deficits in rats recovering from cortical injury

Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride.Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury.The aim of this study was to analyze the role ofα-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage.The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours,3 days,and 20 days after ferrous chloride-induced cortical injury:saline,clonidine,efaroxan(a selective antagonist ofα-adrenergic receptors)and clonidine+efaroxan.The sensorimotor score,the immunohistochemical staining forα-adrenergic receptors,and norepinephrine levels were evaluated.Eight hours post-injury,the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased,and these effects were maintained 3 days post-injury.However,20 days later,clonidine administration diminished norepinephrine levels in the pons compared with the sham group.This effect was accompanied by sensorimotor deficits.These effects were blocked by efaroxan.In conclusion,an increase inα-adrenergic receptor levels was observed after injury.Clonidine restores motor deficits in rats recovering from cortical injury,an effect that was prevented by efaroxan.The underlying mechanisms involve the stimulation of hypersensitiveα-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus.The results of this study suggest thatαreceptor agonists might restore deficits or impede rehabilitation in patients with brain injury,and therefore pharmacological therapies need to be prescribed cautiously to these patients.

通关胶囊对离体人增生前列腺α_1-AR的拮抗作用

目的 :探讨中药通关胶囊治疗前列腺增生 (BPH)的机理。 方法 :运用放射配体结合实验观察通关胶囊对离体人增生前列腺细胞膜α1肾上腺素受体 (α1 AR)的抑制作用。 结果 :通关胶囊对人增生前列腺平滑肌细胞α1 AR与12 5IBE的结合具有竞争抑制作用 ,且呈量效关系 ,其中对中叶增生组织平滑肌细胞α1 AR亲和性最大 [Ki值(2 0 0 .3± 19.83)mg/L]。 结论 :通关胶囊对离体人前列腺细胞膜α1

玫瑰痤疮发病机制和治疗的最新进展

玫瑰痤疮的发病机制复杂,主要与血管舒缩功能障碍、神经血管调节功能异常以及皮肤天然免疫防御功能与屏障功能损害等相关。目前治疗上主要针对其炎症性病理生理过程以及皮肤屏障功能的修复。常用的治疗方法包括外用甲硝唑、壬二酸、伊维菌素、α-肾上腺素能受体激动剂、钙调磷酸酶抑制剂,口服四环素、维甲酸、β-肾上腺素能受体阻滞剂以及联合激光、手术等。本文将综述其发病机制及治疗方面的最新进展,为玫瑰痤疮的诊治提供一定参考。

中枢α受体在脑室注射组胺对颈动脉窦反射重调定中的作用

目的 探讨中枢α1和α2 肾上腺素受体 (α1 AR ,α2 AR)在脑室注射 (icv)组胺 (HA)对颈动脉窦压力感受性反射 (CSR)重调定中的作用。方法 孤离麻醉SD大鼠的双侧颈动脉窦区 ,将不同窦内压 (ISP)与其对应的平均动脉压(MAP)值进行Logistic五参数曲线拟合 ,求得ISP MAP关系曲线及其特征参数 ,观察icvHA以及预先在蓝斑 (LC)或孤束核 (NTS)微量注射α1或α2 AR拮抗剂对CSR的影响。结果 icvHA (6 0 μmol·L-1,5 μl)导致ISP MAP关系曲线后半程明显上移 (P <0 0 5 ) ,ISP和增益关系曲线中部明显下移 (P <0 0 5 ) ,反射参数MAP反射变动范围及反射最大增益减小 (P <0 0 5 ) ;预先向LC注射选择性的α1 AR拮抗剂酚苄明 (PBZ ,3μmol·L-1,5 0 0nl)或α2 AR拮抗剂育亨宾 (YOH ,2 5 μmol·L-1,5 0 0nl) ,均能明显加强HA的上述效应 ,PBZ的这种加强作用不如YOH的显著 (P <0 0 5 ) ;预先向NTS注射相同剂量、容积的PBZ或YOH ,对HA效应的影响与LC注射后的相类似 ,但NTS注射YOH后icvHA所致的阈压变化进一步明显升高 (P <0 0 5 )。结论 脑室给HA使CSR产生快速重调定 ,反射敏感性下降 ;LC与NTS处的α1、α2 AR作用可减弱icvHA对CSR的重调定 ;LC、尤为NTS处的α2