Alpha2-adrenergic activation in the lateral parabrachial nucleus induces NaCl intake under conditions of systemic hyperosmolarity

The inhibition of sodium intake by increased plasma osmolarity may depend on inhibitory mechanisms present in the lateral parabrachial nucleus. Activation of alpha(2)-adrenergic receptors in the lateral parabrachial nucleus is suggested to deactivate inhibitory mechanisms present in this area increasing fluid depletion-induced 0.3 M NaCl intake. Considering the possibility that lateral parabrachial nucleus inhibitory mechanisms are activated and restrain sodium intake in animals with increased plasma osmolarity, in the present study we investigated the effects on water and 0.3 M NaCl intake produced by the activation of alpha(2)-adrenergic receptors in the lateral parabrachial nucleus in rats with increased plasma osmolarity. Male Holtzman rats with stainless steel cannulas implanted bilaterally into the lateral parabrachial nucleus were used. One hour after intragastric 2 M NaCl load (2 ml), bilateral injections of moxonidine (alpha(2)-adrenergic/imidazoline receptor agonist, 0.5 nmol/0.2 microl, n=10) into the lateral parabrachial nucleus induced a strong ingestion of 0.3 M NaCl intake (19.1+/-5.5 ml/2 h vs. vehicle: 1.8+/-0.6 ml/2 h), without changing water intake (15.8+/-3.0 ml/2 h vs. vehicle: 9.3+/-2.0 ml/2 h). However, moxonidine into the lateral parabrachial nucleus in satiated rats not treated with 2 M NaCl produced no change on 0.3 M NaCl intake. The pre-treatment with RX 821002 (alpha(2)-adrenergic receptor antagonist, 20 nmol/0.2 microl) into the lateral parabrachial nucleus almost abolished the effects of moxonidine on 0.3 M NaCl intake (4.7+/-3.4 ml/2 h). The present results suggest that alpha(2)-adrenergic receptor activation in the lateral parabrachial nucleus blocks inhibitory mechanisms, thereby allowing ingestion of hypertonic NaCl under conditions of extracellular hyperosmolarity. We suggest that during cell dehydration, circuits subserving sodium appetite are activated, but at the same time strongly inhibited through the lateral parabrachial nucleus.     

《金匮要略》治疗糖尿病探析

糖尿病属中医学"消渴"范畴。"消渴"首载于《素问·奇病论》,辨证论治则始于《金匮要略》。糖尿病早期患者常有热盛津伤的表现,治疗当以清热生津、益气养阴为法,常用白虎汤类方;糖尿病肾功能失代偿期及尿毒症期患者常因肾气虚弱、气化不畅而致开阖失司、湿浊停聚,治疗当以温阳化气、利水渗湿为法,常用五苓散类方;糖尿病引发各种并发症多由气机失调、痰热瘀滞引起,治疗当从肝入手,缓肝调中、滋阴泻热,常用乌梅丸类方;糖尿病肾病合并血管病变或神经病变多因久病伤津耗气而致气阴两虚,气虚则无力推血运行,治疗当活血化瘀,生津止渴,常用桃核承气汤类方。     

中医药治疗2型糖尿病的现代生物学

2型糖尿病是全世界的健康难题,西医西药在治疗糖尿病中存在局限性,中医治疗糖尿病历史悠久,其整体观念和辨证论治更符合系统生物学对糖尿病的认识,在糖尿病的治疗中具有重要的价值。但是由于文化背景不同和科学技术的限制,中医药治疗糖尿病的疗效和机制还未被国际广泛认可。中医病机与疾病的病理生理机制能够用现代生物学理论有机的联系起来,用中西医结合观认识糖尿病,用现代生物学理论去解释病因病机、法理方药,用组学、质谱技术、基因测序技术等破解对中医药糖尿病治疗中的科学疑问,把中医的精华展现出来,为中医药治疗糖尿病的研究提供理论依据。     

糖尿病性骨质疏松的中医药防治

随着糖尿病的发病率逐年增加,直接导致糖尿病性骨质疏松的发病率也随之上升,并且本病容易引起骨折等不良后果,严重影响患者生命质量,并带来巨大经济负担。目前DOP的治疗,主要以抗骨质疏松药物治疗为主,然而此类药物治疗效果仍存在争议,且价格昂贵,有些患者对其不良反应不能耐受。目前急需对糖尿病骨质疏松的发生机制进行研究,并寻找更经济有效的治疗方法。由此,中药的抗骨质疏松作用逐渐受到重视。中医药治疗糖尿病的大量实验和临床研究,肯定了中医药的疗效,中药或中西药结合已经在临床上非常普遍应用。现从糖尿病骨质疏松的病因病机、辨证论治、动物实验及临床研究等方面的研究进展进行综述。     

张发荣从“渴”论治消渴经验

张发荣教授研究消渴病多年,不拘泥于"三消"定位论治消渴,提出从"渴"角度论治消渴病之思路,认为消渴病之口渴可因阴液本少、失于输布、多脏亏损而致。阴液本少,临床可分期论治。津液输布失常,分别针对偏于气虚、气滞、水湿、痰饮、血瘀等不同原因所致口渴采用攻补兼施之法。脏腑亏虚,则从脾或从肾论治,病久则脾肾同调。     

Selective catecholamine depletion of structures along the ventral lamina terminalis: effects on experimentally-induced drinking and pressor responses

Ablation of the periventricular tissue of the anteroventral third ventricle (AV3V) or injection of the chemical neurotoxin, 6-hydroxydopamine (6-OHDA), into the structures along the ventral lamina terminalis will produce deficits in drinking and pressor responses to exogenous angiotensin II (ANG II). Centrally-applied 6-OHDA has been shown to result in widespread depletions of both adrenergic (i.e. both noradrenaline and adrenaline-containing) and dopaminergic neurons. Questions arise, therefore, as to whether a dopaminergic or adrenergic depletion is critical and the locus where reductions must occur. The present experiment was designed to investigate the specificity of the effects of 6-OHDA administration into lamina terminalis-associated structures on ANG II-induced drinking and pressor responses. The nature of the depletion was manipulated with desmethylimipramine (DMI), a drug which blocks the uptake of 6-OHDA into adrenergic but not dopaminergic nerve terminals and thereby spares adrenergic elements. The experimental results indicate that 6-OHDA administration into structures of the ventral lamina terminalis produced ANG II response deficits and marked reductions in catecholamine histofluorescence in the regions of the injection sites. In contrast, pretreatment with DMI protected against the 6-OHDA-produced functional deficits and minimized the effects on histofluorescence. These findings are consistent with the interpretation that adrenergic but not dopaminergic neurons must be present in the structures of the ventral lamina terminalis in order to elicit normal angiotensin-induced drinking and pressor responses.     

Recumbent Cranial Diabetes Insipidus

ABSTRACT. A male, aged 16, with chronic Hypernatremia, adipsia, polyphagia, and poikilothermia was studied regarding regulation and secretion of arginine vasopressin. During recumbency at night, low plasma arginine vasopressin levels and increased volumes of dilute urine were found; whereas plasma arginine vasopressin levels and urine osmolalities rose and urine volumes decreased during ambulation in the daytime. Neither a 25% reduction of mean arterial pressure nor hypertonic saline infusion increased plasma arginine vasopressin or urine osmolalities. Treatment with 1-desamino-D-arginine-vasopressin at 6 p.m. and a scheduled fluid intake according to actual body weight eradicated Hypernatremia and hyperosmolality. These data demonstrate a complete loss of arginine vasopressin secretion to osmotic stimulation, a partial defect of arginine vasopressin secretion to non-osmotic stimulation, an abolished response to stimulation of high-pressure-baroreceptors, but an intact responsiveness to stimulation of low-pressure-baroreceptors.     

Clonidine antagonism of angiotensin-related drinking: a central site of action

Administration of either isoproterenol (25 μg/kg, s.c.) or angiotensin II (200 μg/kg, s.c.) induces drinking in rats within 0.5–1 h. This drinking was inhibited by prior administration of the presynaptic α-adrenergic agonist clonidine (12 μg/kg, i.p.). Urine output was enhanced by clonidine in the angiotensin II-, but not the isoproterenol-treated group. Drinking in response to peripheral administration of either angiotensin II or isoproterenol was also inhibited by intracerebroventricular (i.v.t.) administration of clonidine (8 μ/kg). This dose of clonidine also enhanced the urine output after angiotensin II. Further, the drinking induced by i.v.t. administration of angiotensin II, at 4 but not 20 ng/kg was inhibited by peripheral administration of clonidine (12 μg/kg, i.p.). When clonidine was administered i.v.t. prior to i.v.t. injection of either angiotensin II (20 ng/kg) or carbachol (1.2 μg/kg), the drinking response to these dipsogens was attenuated. These results suggest that clonidine may act centrally to attenuate drinking at a site, possibly in the nucleus tractus solitarius, that may be considered a final common pathway for this response.     

Fetal noradrenergic transplants into amine-depleted basal forebrain nuclei restore drinking to angiotensin

6-Hydroxydopamine-induced catecholamine denervations in the organum vasculosum of the lamina terminalis and the median preoptic nucleus attenuate drinking responses to systemic angiotensin II (ANG II) injections. Transplanting catecholamines in these nuclei using fetal noradrenergic (NE) cell suspension restores ANG II-elicited thirst. These results emphasize the functional importance of NE neuronal systems in nuclei of the anteroventral third ventricle (AV3V) in mediating ANG II-induced drinking behaviors.