nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure

We hypothesized that gene transfer of neuronal nitric oxide synthase (nNOS) into the rostral ventrolateral medulla (RVLM) improves baroreflex function in rats with chronic heart failure (CHF). Six to eight weeks after coronary artery ligation, rats showed hemodynamic signs of CHF. A recombinant adenovirus, either Ad.nNOS or Ad.beta-Gal, was transfected into the RVLM. nNOS expression in the RVLM was confirmed by Western blot analysis, NADPH-diaphorase, and immunohistochemical staining. We studied baroreflex control of the heart rate (HR) and renal sympathetic nerve activity (RSNA) in the anesthetized state 3 days after gene transfer by intravenous injections of phenylephrine and nitroprusside. Baroreflex sensitivity was depressed for HR and RSNA regulation in CHF rats (2.0 +/- 0.3 vs. 0.8 +/- 0.2 beats.min-1.mmHg-1, P < 0.01 and 3.8 +/- 0.3 vs. 1.2 +/- 0.1% max/mmHg, P < 0.01, respectively). Ad.nNOS transfer into RVLM significantly increased the HR and RSNA ranges (152 +/- 19 vs. 94 +/- 12 beats/min, P < 0.05 and 130 +/- 16 vs. 106 +/- 5% max/mmHg, P < 0.05) compared with the Ad.beta-Gal in CHF rats. Ad.nNOS also improved the baroreflex gain for the control of HR and RSNA (1.8 +/- 0.2 vs. 0.8 +/- 0.2 beats.min-1.mmHg-1, P < 0.01 and 2.6 +/- 0.2 vs. 1.2 +/- 0.1% max/mmHg, P < 0.01). In sham-operated rats, we found that Ad.nNOS transfer enhanced the HR range compared with Ad.beta-Gal gene transfer (188 +/- 15 vs. 127 +/- 14 beats/min, P < 0.05) but did not alter any other parameter. This study represents the first demonstration of altered baroreflex function following increases in central nNOS in the CHF state. We conclude that delivery of Ad.nNOS into the RVLM improves baroreflex function in rats with CHF.     

Dysfunction of the mitochondrial respiratory chain in the rostral ventrolateral medulla during experimental endotoxemia in the rat

We investigated the functional changes in the mitochondrial respiratory chain at the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor tone, in an experimental model of endotoxemia that mimics systemic inflammatory response syndrome. In Sprague-Dawley rats maintained under propofol anesthesia, intravenous administration ofEscherichia coli lipopolysaccharide (LPS; 30 mg/kg) induced a reduction (Phase I), followed by an augmentation (Phase II) and a secondary decrease (Phase III) in the power density of vasomotor components (0–0.8 Hz) in systemic arterial pressure signals. LPS also elicited progressive hypotension, and death ensued within 4 h. Enzyme assay revealed significant depression of the activity of nicotinamide adenine dinucleotide cytochromec reductase (Complexes I + III) and cytochromec oxidase (Complex IV) in the RVLM during all three phases of endotoxemia. On the other hand, the activity of succinate cytochromec reductase (Complexes II + III) remained unaltered. We conclude that selective dysfunction of respiratory enzyme Complexes I and IV in the mitochondrial respiratory chain at the RVLM, whose neuronal activity is intimately related to the death process, is closely associated with fatal endotoxemia in the rat.     

The anaesthetic agent propofol interacts with GABA(B)-receptors: an electrophysiological study in rat

The mode of action by which propofol induces anaesthesia is not fully understood, although several studies suggest that the compound acts via potentiation of brain GABA(A)-receptors. The aim of the present study is to investigate a putative GABA(B)-receptor agonistic action of propofol. For this purpose the action of propofol on a GABA-receptor mediated regulation of dopamine neurons was analyzed with extracellular single unit recordings of dopaminergic neurons of the substantia nigra in chloral hydrate anaesthetized rats.Intravenous administration of propofol (1-16 mg/kg) was found to dose-dependently decrease the firing rate and burst firing activity of nigral DA neurons. These effects by propofol were effectively antagonized by pretreatment with the selective GABA(B)-receptor antagonist CGP 35348 (200 mg/kg, i.v.) but not by pretreatment with the GABA(A)-receptor antagonist picrotoxin (4.5 mg/kg, i.v.).It is proposed that an activation of central GABA(B)-receptors may, at least partially, contribute to the anesthetic properties of propofol.     

Comparison of spontaneous activity of mesencephalic reticular neurones in the waking state and during pentobarbital anaesthesia.

In rats immobilized by d-Tubocurarine the spontaneous activity of 100 mesencephalic reticular neurones was recorded extracellularly and statistically evaluated before and after repeated intravenous administration of 15 mg/kg doses of Pentobarbital. Number of spontaneously active neurones decreases quasi-linearly with repeated 15 mg/kg Pentobarbital doses. After a 75 mg/kg cumulative dose practically all neurones ceased firing spontaneously, whereas cortical EEG activity fully disappeared after the 90 mg/kg Pentobarbital dose. The firing rate was characterized by the mean interval with its standard deviation. Mean value for the total sample of spontaneously active neurones was 146.7 +/- 192.3 msec without Pentobarbital and increased to 302.7 +/- 367.5 msec after 15 mg/kg and to 400.6 +/- 452.5 msec after 30 mg/kg cumulative dose of Pentobarbital. The 15 mg/kg dose increased the frequency of firing in 5% of neurones only. The most often encountered type of interval histogram in the mesencephalic reticular formation was the exponential type (59% in unanaesthetized state), which was also most sensitive to Pentobarbital. Synchronized activity in bursts, characterized by periodical peaks and dips frequently occurred in neurones with the exponential-like interspike interval density after Pentobarbital administration. On the contrary, neurones with gamma-like and especially with symmetrical-like types of density were less influenced by Pentobarbital. In many neurones a periodical increase in the firing rate (with intervals of tens of seconds) related to the occurrence of spindles was present in the cortical EEG activity.     

Effects of neuronal norepinephrine uptake blockade on baroreflex neural and peripheral arc transfer characteristics

Neuronal uptake is the most important mechanism by which norepinephrine (NE) is removed from the synaptic clefts at sympathetic nerve terminals. We examined the effects of neuronal NE uptake blockade on the dynamic sympathetic regulation of the arterial baroreflex because dynamic characteristics are important for understanding the system behavior in response to exogenous disturbance. We perturbed intracarotid sinus pressure (CSP) according to a binary white noise sequence in anesthetized rabbits, while recording cardiac sympathetic nerve activity (SNA), arterial pressure (AP), and heart rate (HR). Intravenous administration of desipramine (1 mg/kg) decreased the normalized gain of the neural arc transfer function from CSP to SNA relative to untreated control (1.03 +/- 0.09 vs. 0.60 +/- 0.08 AU/mmHg, mean +/- SE, P < 0.01) but did not affect that of the peripheral arc transfer function from SNA to AP (1.10 +/- 0.05 vs. 1.08 +/- 0.10 mmHg/AU). The normalized gain of the transfer function from SNA to HR was unaffected (1.01 +/- 0.04 vs. 1.09 +/- 0.12 beats.min(-1).AU(-1)). Desipramine decreased the natural frequency of the transfer function from SNA to AP by 28.7 +/- 7.0% (0.046 +/- 0.007 vs. 0.031 +/- 0.002 Hz, P < 0.05) and that of the transfer function from SNA to HR by 64.4 +/- 2.2% (0.071 +/- 0.003 vs. 0.025 +/- 0.002 Hz, P < 0.01). In conclusion, neuronal NE uptake blockade by intravenous desipramine administration reduced the total buffering capacity of the arterial baroreflex mainly through its action on the neural arc. The differential effects of neuronal NE uptake blockade on the dynamic AP and HR responses to SNA may provide clues for understanding the complex pathophysiology of cardiovascular diseases associated with neuronal NE uptake deficiency.     

Baroreflex modulation by angiotensins at the rat rostral and caudal ventrolateral medulla

We determined the effect of microinjection of ANG-(1-7) and ANG II into two key regions of the medulla that control the circulation [rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively)] on baroreflex control of heart rate (HR) in anesthetized rats. Reflex bradycardia and tachycardia were induced by increases and decreases in mean arterial pressure produced by intravenous phenylephrine and sodium nitroprusside, respectively. The pressor effects of ANG-(1-7) and ANG II (25 pmol) after RVLM microinjection (11 +/- 0.8 and 10 +/- 2 mmHg, respectively) were not accompanied by consistent changes in HR. In addition, RVLM microinjection of these angiotensin peptides did not alter the bradycardic or tachycardic component of the baroreflex. CVLM microinjections of ANG-(1-7) and ANG II produced hypotension (-11 +/- 1.5 and -11 +/- 1.9 mmHg, respectively) that was similarly not accompanied by significant changes in HR. However, CVLM microinjections of angiotensins induced differential changes in the baroreflex control of HR. ANG-(1-7) attenuated the baroreflex bradycardia (0.26 +/- 0.06 ms/mmHg vs. 0.42 +/- 0.08 ms/mmHg before treatment) and facilitated the baroreflex tachycardia (0.86 +/- 0.19 ms/mmHg vs. 0.42 +/- 0.10 ms/mmHg before treatment); ANG II produced the opposite effect, attenuating baroreflex tachycardia (0.09 +/- 0.06 ms/mmHg vs. 0.31 +/- 0.07 ms/mmHg before treatment) and facilitating the baroreflex bradycardia (0.67 +/- 0.16 ms/mmHg vs. 0.41 +/- 0.05 ms/mmHg before treatment). The modulatory effect of ANG II and ANG-(1-7) on baroreflex sensitivity was completely abolished by peripheral administration of methylatropine. These results suggest that ANG II and ANG-(1-7) at the CVLM produce a differential modulation of the baroreflex control of HR, probably through distinct effects on the parasympathetic drive to the heart.     

γ-氨基丁酸对离体大鼠延髓头端腹外侧区神经元单位放电的抑制作用

在７３张脑片上观察了γ－氨基丁酸（ＧＡＢＡ）对１０６个延髓头端腹外侧区（ＲＶＬＭ）神经元单位放电的影响。外源性的ＧＡＢＡ（０．１￣３．０ｍｍｏｌ／Ｌ）抑制了１０６神经元中的８４个神经元的电活动,这些抑制效应呈剂量－反应关系。ＧＡＢＡ的抑制效应大部分可被ＧＡＢＡＡ受体选择性拮抗剂荷苞牡丹碱甲基碘化物（ＢＭＩ）和Ｃｌ＾－通道阻断剂印防己毒素（ＰＴＸ）所阻断,而单独灌流ＢＭＩ和ＰＴＸ对ＲＶＬＭ神经元主要     

Effect of hypercholesterolemia on Ca(2+)-dependent K(+) channel-mediated vasodilatation in vivo

Nitric oxide (NO)-mediated and NO-independent mechanisms of endothelium-dependent vasodilatation involve Ca(2+)-dependent K(+) (K(Ca)) channels. We examined the role in vivo of K(Ca) channels in NO-independent vasodilatation in hypercholesterolemia. Hindlimb vascular conductance was measured at rest and after aortic injection of ACh, bradykinin (BK), and sodium nitroprusside in anesthetized control and cholesterol-fed rabbits. Conductances were measured before and after treatment with the NO synthase antagonist N(omega)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) or K(Ca) blockers tetraethylammonium (30 mg/kg), charybdotoxin (10 microgram/kg), and apamin (50 microgram/kg). The contribution of NO to basal conductance was greater in control than in cholesterol-fed rabbits [2.2 +/- 0.4 vs. 1.1 +/- 0.3 (SE) ml. min(-1). kg(-1). 100 mmHg(-1), P < 0.05], but the NO-independent K(Ca) channel-mediated component was greater in the cholesterol-fed than in the control group (1.1 + 0.4 vs. 0.3 +/- 0.1 ml. min(-1). kg(-1). 100 mmHg(-1), P < 0.05). Maximum conductance response to ACh and BK was less in cholesterol-fed than in control rabbits, and the difference persisted after L-NAME (ACh: 7.7 +/- 0.7 vs. 10.1 +/- 0.5 ml. min(-1). kg(-1). 100 mmHg(-1), P < 0.005). Blockade of K(Ca) channels with tetraethylammonium or charybdotoxin + apamin almost completely abolished L-NAME-resistant vasodilatation after ACh or BK. The magnitude of K(Ca)-mediated vasodilatation after ACh or BK was impaired in hypercholesterolemic rabbits. Vasodilator responses to nitroprusside did not differ between groups. In vivo, hypercholesterolemia is associated with an altered balance between NO-mediated and NO-independent K(Ca) channel contributions to resting vasomotor tone and impairment of both mechanisms of endothelium-dependent vasodilatation.     

CCK-induced inhibition of presympathetic vasomotor neurons: dependence on subdiaphragmatic vagal afferents and central NMDA receptors in the rat

Systemic administration of cholecystokinin (CCK) inhibits a subpopulation of rostral ventrolateral medulla (RVLM) presympathetic vasomotor neurons. This study was designed to determine whether this effect involved subdiaphragmatic vagal afferents and/or central N-methyl-d-aspartic acid (NMDA) receptors. Recordings were made from CCK-sensitive RVLM presympathetic vasomotor neurons in halothane-anesthetized, paralyzed male Sprague-Dawley rats. The responses of the neurons to CCK (2 and 4 microg/kg iv), phenylephrine (PE; 5 microg/kg iv), and phenylbiguanide (PBG; 5 microg/kg iv) were tested before and after application of the local anesthetic lidocaine (2% wt/vol gel; 1 ml) to the subdiaphragmatic vagi at the level of the esophagus. In seven separate experiments, lidocaine markedly reduced the inhibitory effects of CCK on RVLM presympathetic neuronal discharge rate. In other experiments, the effect of systemic administration of dizocilpine (1 mg/kg iv), a noncompetitive antagonist at NMDA receptor ion channels, on the RVLM presympathetic neuronal responses to CCK, PBG, and PE was tested. In all cases (n = 6 neurons in 6 individual rats), dizocilpine inhibited the effects of CCK, PBG, and PE on RVLM presympathetic neuronal discharge. These results suggest that the effects of systemic CCK on the discharge of RVLM presympathetic neurons is mediated via an action on receptors located on subdiaphragmatic vagal afferents. Furthermore, the data suggest that CCK activates a central pathway involving NMDA receptors to produce inhibition of RVLM presympathetic neuronal discharge.     

选择性5-HT1A受体拮抗剂WAY-100635增加6-羟多巴胺损毁大鼠杏仁基底外侧核的神经活动

本文采用玻璃微电极细胞外记录法,观察正常大鼠和6-羟多巴胺(6-hydroxydopamine,6-OHDA)损毁黑质致密部大鼠杏仁基底外侧核(basolateral nucleus,BL)神经元电活动的变化,以及体循环给予选择性5-HT1A受体拮抗剂WAY-100635对神经元电活动的影响.结果显示,正常大鼠BL投射神经元和中间神经元的放电频率分别足(O.39±0.04)Hz和(0.83±0.16)Hz,6-OHDA损毁大鼠BL投射神经元和中间神经元的放电频率分别足(0.32±0.04)Hz和(0.53±0.12)Hz,与正常大鼠相比无显著差异.在正常大鼠,所有投射神经元呈现爆发式放电;94%的中间神经元为爆发式放电,6%为不规则放电.在6.OHDA损毁大鼠,85%的投射神经元呈现爆发式放电,15%为不规则放电;86%的中间神经元为爆发式放电,14%为不规则放电,与正常大鼠相比无显著差别.静脉给予0.1 mg/kg体重的WAY-100635不改变正常大鼠和6-OHDA损毁人鼠BL投射神经元和中间神经元的放电频率.然而,0.5 mg/kg体重的WAY-100635却显著降低正常大鼠BL投射神经元的平均放电频率(P<0.01),明显增加6-OHDA损毁大鼠BL投射神经元的平均放电频率(P<0.004).高剂量WAY-100635不影响正常大鼠和6-OHDA损毁大鼠BL中间神经元的平均放电频率.结果表明,黑质多巴胺能损毁后内在和外在的传入调节BL神经元的活动,在正常大鼠和6-OHDA损毁大鼠5-HT1A 受体调节投射神经元的活动,并且在6-OHDA损毁大鼠WAY-100635诱发投射神经元平均放电频率增加.结果提示,5-HT1A 受体在帕金森病情感性症状的产生中起重要作用.     

A comparison of medetomidine-propofol and medetomidine-midazolam-propofol anesthesia in rabbits.

We evaluated and compared the effects of medetomidine-propofol and medetomidine-midazolam-propofol anesthesia in rabbits. Fourteen New Zealand White rabbits were randomly assigned to receive either medetomidine (0.25 mg/kg, i.m.)-atropine (0.5 mg/kg, i.m.)-propofol (4 mg/kg, i.v.) (n = 7) or medetomidine (0.25 mg/kg, i.m.)-atropine (0.5 mg/kg, i.m.)-midazolam (0.5 mg/kg, i.m.)-propofol (2 mg/kg, i.v.) (n = 7). Five minutes after medetomidine-atropine or medetomidine-atropine-midazolam i.m. injection, propofol was administered i.v. Both medetomidine and medetomidine-midazolam rapidly (within 5 minutes) immobilized all rabbits and greatly eased the i.v. administration of propofol. Endotracheal intubation was accomplished easily after propofol injection in both groups. There was no significant difference between medetomidine-propofol and medetomidine-midazolam-propofol-treated rabbits in heart rate, respiratory rate, mean arterial pressure, or end-tidal CO2. The addition of midazolam to the medetomidine-propofol regimen significantly (P < 0.05) prolonged the duration of ear-pinch analgesia (25.0 +/- 7.1 vs. 36.7 +/- 8.9 minutes), the time from extubation to sternal recumbency (0.0 vs. 26.7 +/- 8.1 minutes), and the time from extubation to standing (0.0 vs. 39.5 +/- 11.3 minutes) without inducing significant changes in arterial blood pressure and end-tidal alveolar CO2. We consider both medetomidine-propofol and medetomidine-midazolam-propofol combinations to be safe and effective regimens for induction and short-term anesthesia in rabbits.     

Interactions of plasma osmolality with arterial and central venous pressures in control of sympathetic activity and heart rate in humans

Plasma osmolality alters control of sympathetic activity and heart rate in animal models; however, it is unknown whether physiological increases in plasma osmolality have such influences in humans and what effect concurrent changes in central venous and/or arterial pressures may have. We tested whether physiological increases in plasma osmolality (similar to those during exercise dehydration) alter control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) in humans. We studied 17 healthy young adults (7 women, 10 men) at baseline and during arterial pressure (AP) transients induced by sequential injections of nitroprusside and phenylephrine, under three conditions: control (C), after 1 ml/kg intravenous hypertonic saline (HT1), and after 2 ml/kg hypertonic saline (HT2). We continuously measured HR, AP, central venous pressure (CVP; peripherally inserted central catheter) and MSNA (peroneal microneurography) in all conditions. Plasma osmolality increased from 287 +/- 1 mosmol/kg in C to 290 +/- 1 mosmol/kg in HT1 (P < 0.05) but did not increase further in HT2 (291 +/- 1 mosmol/kg; P > 0.05 vs. C). Mean AP and CVP were similar between C and HT1, but both increased slightly in HT2. HR increased slightly but significantly during both HT1 and HT2 vs. C (P < 0.05). Sensitivity of baroreflex control of MSNA was significantly increased vs. C in HT1 [-7.59 +/- 0.97 (HT1) vs. -5.85 +/- 0.63 (C) arbitrary units (au).beat(-1).mmHg(-1); P < 0.01] but was not different in HT2 (-6.55 +/- 0.94 au.beat(-1).mmHg(-1)). We conclude that physiological changes in plasma osmolality significantly alter control of MSNA and HR in humans, and that this influence can be modified by CVP and AP.     

颈动脉注射17β -雌二醇对去缓冲神经大鼠延髓腹外侧头端区神经元放电活动的影响

本研究旨在观察17β-雌二醇(E2)对雄性大鼠延髓腹外侧头端区(RVLM)神经元自发放电活动的影响.在切断双侧缓冲神经的麻醉雄性Sprague-Dawley大鼠上,同步记录血压、心率和RVLM神经元的自发放电活动.颈动脉内注射E2 (10 ng/kg),30个RVLM神经元自发放电单位中有25个单位的放电频率由14.46±0.47降至9.73±0.33 spikes/s (P<0.05),与此同时血压和心率无明显改变.E2的抑制效应在1 min内起效,持续时间长于5 min.雌激素受体拮抗剂tamoxifen (5 mg/kg)不能阻断E2 的抑制效应.预先给予一氧化氮(NO)合酶阻断剂L-NAME (2.7 μg/kg)能明显阻断E2的抑制效应.应用NO供体SIN-1 (0.5 μg/kg)可增强E2的抑制效应.以上结果提示,E2可通过非基因组效应激活RVLM神经元的NOS而引发NO释放,进而抑制其自发放电活动.     

异丙酚复合芬太尼静脉麻醉镇痛对门诊人工流产术的影响

目的:观察异丙酚复合芬太尼静脉麻醉对于人工流产术时及术后的影响。方法:选择2001年3月——2001年9月在本院计划生育门诊就诊、自愿要求无痛人工流产的妇女120例作为无痛人工流产组(简称:无痛组),同期按常规方法行人工流产的妇女120例作为对照组(简称:对照组),进行配对研究。无痛组用异丙酚1.5mg/kg复合芬太尼2μg/kg诱导,术中用异丙酚维持,人工流产术按常规方法施行。结果:无痛组术中异丙酚用量为2.7±0.7mg/kg,芬太尼2μg/kg,术中无知觉,120例妇女均无疼痛主诉。对照组轻度疼痛82例(68.3％),中度疼痛33例(27.5％),重度疼痛3例(4.2％)。无痛组在麻醉诱导及维持期间均出现呼吸频率下降,通过控制呼吸、面罩吸氧,SaO_2可以保持在99％以上,不需气管插管。两组妇女术前及术后宫腔深度无明显差异(P>0.05)。无痛组术中出血量为32.2±23.2ml,对照组为19.8±15.9ml,无痛组较对照组明显增多,有极显著统计学差异(P<0.01)。结论:异丙酚复合芬太尼静脉麻醉对人工流产术的主要影响是手术的出血量略增多,但不影响子宫收缩及术后恶露持续时间,该麻醉是一种有效镇痛方法,适用于门诊人工流产术。     

内皮素通过最后区易化大鼠延髓腹外侧头端区神经元活动

在３５只切断双侧缓冲神经、用氨基甲酸乙酯－α氯醛糖混合麻醉的Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠,应用细胞外记录的电生理学方法,由ＲＭ－６０００型多道生理记录仪和ＷＳ－６８２Ｇ热阵记录器（频响范围０～２．８ｋＨｚ）同步记录血压、心率和单位神经元放电,观察颈动脉注射内皮素对８７个延髓腹是头端区（ＲＶＬＭ）自发放电神经元活动的影响,所得结果如下;（１）颈动脉注射ＥＴ－１（０．３ｎｍｏｌ／ｋｇ）时３６个单位     

Parasympathetic non-adrenergic, non-cholinergic transmission in rat parotid glands: effects of cholecystokinin-A and -B receptor antagonists on the secretory response

Recent studies show i.v. administered pentagastrin and cholecystokinin to evoke protein/amylase secretion from the rat parotid gland and to stimulate gland protein synthesis, the two phenomena being abolished by cholecystokinin receptor antagonists. In the rat parotid gland, non-adrenergic, non-cholinergic transmission mechanisms contribute to secretion of fluid and protein/amylase. Since cholecystokinin may act as a neurotransmitter, activation of cholecystokinin receptors of the gland might contribute to the parasympathetic nerve-evoked secretion. In this study, the parasympathetic innervation was stimulated in non-atropinized (in periods of 2 min) or atropinized (in periods of 3 min) pentobarbitone-anaesthetized rats before and after administration of the cholecystokinin-A receptor antagonist lorglumide (48 mg/kg, i.v.) and the cholecystokinin-B receptor antagonist itriglumide (5.5 mg/kg, i.v.). The non-adrenergic, non-cholinergic transmission fatigues rapidly resulting in declining responses. Therefore, atropinized rats, not receiving the cholecystokinin receptor antagonists, had to serve as controls. Neither at a stimulation frequency of 10 Hz nor of 40 Hz were the secretory responses of the atropinized rats affected by the receptor antagonists. After lorglumide, the saliva volume and the amylase output were (expressed as percentage of the response to the stimulation period before the administration of the antagonist) 98.0+/-3.8% (vs. control 91.1+/-4.0%) and 91.9+/-4.9% (vs. 87.7+/-3.7%) at 10 Hz, respectively, and 79.8+/-4.5% (vs. 77.3+/-2.1%) and 73.6+/-5.3% (vs. 71.7+/-2.3%) at 40 Hz, respectively. After itriglumide, the corresponding percentage figures for saliva volume and amylase output were, at 10 Hz, 99.5+/-8.9% (vs. 92.0+/-2.8%) and 95.8+/-11.8% (vs. 89.2+/-6.4%), respectively, and, at 40 Hz, 74.0+/-3.1% (vs. 79.6+/-2.2%) and 66.6+/-3.3% (vs. 63.9+/-6.0%), respectively. Similarly, the antagonists were without effect on the parotid secretory responses of non-atropinized rats subjected to stimulation at 10 Hz. Thus, under physiological conditions, the cholecystokinin receptors of the parotid gland are likely to be stimulated by circulating hormones rather than by nervous activity.     

Physical exercise decreases neuronal activity in the posterior hypothalamic area of spontaneously hypertensive rats.

Recently, physical exercise has been shown to significantly alter neurochemistry and neuronal function and to increase neurogenesis in discrete brain regions. Although we have documented that physical exercise leads to molecular changes in the posterior hypothalamic area (PHA), the impact on neuronal activity is unknown. The purpose of the present study was to determine whether neuronal activity in the PHA is altered by physical exercise. Spontaneously hypertensive rats (SHR) were allowed free access to running wheels for a period of 10 wk (exercised group) or no wheel access at all (nonexercised group). Single-unit extracellular recordings were made in anesthetized in vivo whole animal preparations or in vitro brain slice preparations. The spontaneous firing rates of PHA neurons in exercised SHR in vivo were significantly lower (8.5 +/- 1.6 Hz, n = 31 neurons) compared with that of nonexercised SHR in vivo (13.7 +/- 1.8 Hz, n = 38 neurons; P < 0.05). In addition, PHA neurons that possessed a cardiac-related rhythm in exercised SHR fired significantly lower (6.0 +/- 1.8 Hz, n = 11 neurons) compared with nonexercised SHR (12.1 +/- 2.4 Hz, n = 18 neurons; P < 0.05). Similarly, the spontaneous in vitro firing rates of PHA neurons from exercised SHR were significantly lower (3.5 +/- 0.3 Hz, n = 67 neurons) compared with those of nonexercised SHR (5.6 +/- 0.5 Hz, n = 58 neurons; P < 0.001). Both the in vivo and in vitro findings support the hypothesis that physical exercise can lower spontaneous activity of neurons in a cardiovascular regulatory region of the brain. Thus physical exercise may alter central neural control of cardiovascular function by inducing lasting changes in neuronal activity.     

Effects of vasomotor- and mediator-induced hypotension on bronchomotor tone in swine

We studied the sympathetic neural response on airways to hypotensive stimuli in 19 swine in vivo. The effects of pharmacologically induced hypotension with nitroprusside (NTP) and hypotension elicited by intravenous compound 48/80 (48/80), a mast cell degranulating agent, were compared after equivalent reductions in mean arterial blood pressure (MAP). Reduction of the MAP to 60% of base line with NTP in six swine caused an increase in plasma epinephrine (E) from 60 +/- 28 to 705 +/- 276 pg/ml (P = 0.032) and plasma norepinephrine (NE) from 270 +/- 46 to 796 +/- 131 pg/ml (P = 0.032). Comparable reduction in MAP elicited with 48/80 in six other swine caused a substantially greater increase in both plasma E (9,581 +/- 4,147 pg/ml; P = 0.012 vs. NTP group) and plasma NE (2,239 +/- 637 pg/ml; P = 0.041 vs. NTP group). Catecholamine secretion attenuated mediator-induced changes in lung resistance (RL). In animals receiving 48/80, RL increased from 2.97 +/- 0.31 to 7.44 +/- 0.56 cmH2O.l-1.s. In animals having ganglionic blockade with 7.5 mg/kg iv hexamethonium and beta-adrenergic blockade with propranolol (4.0 mg/kg iv followed by 40 micrograms/kg-1.min-1), comparable doses of 48/80 caused an increase in RL to 18.6 +/- 4.55 cmH2O.l-1.s (P less than 0.04 vs. swine receiving neither hexamethonium nor propranolol).(ABSTRACT TRUNCATED AT 250 WORDS)     

Early gestation dexamethasone alters baroreflex and vascular responses in newborn lambs before hypertension

Exposure of the early gestation ovine fetus to exogenous glucocorticoids induces alterations in postnatal cardiovascular physiology, including hypertension. To determine whether autonomic function and systemic vascular reactivity are altered by in utero programming before the development of systemic hypertension, we examined arterial baroreflex function and in vivo hemodynamic and in vitro vascular responses to vasoactive agents in 10- to 14-day-old newborn lambs exposed to early gestation glucocorticoids. Dexamethasone (Dex, 0.28 mg.kg-1.day-1) or saline was administered to pregnant ewes by intravenous infusion over 48 h beginning at 27 days gestation (term 145 days), and lambs were allowed to deliver (n=6 in each group). Resting mean arterial blood pressure (MABP; 77+/-1 vs. 74+/-3 mmHg) and heart rate (HR; 249+/-9 vs. 226+/-21 beats/min) were similar in Dex-exposed and control animals, respectively. The arterial baroreflex curve, relating changes in HR to MABP, was significantly shifted toward higher pressure in the Dex-exposed lambs although no change in the sensitivity (gain) of the response was seen. In vivo changes in blood pressure in response to bolus doses of ANG II (20, 50, and 100 ng/kg) and phenylephrine (2, 5, and 10 microg/kg) were similar in the two groups. However, Dex lambs displayed greater decreases in MABP in response to ganglionic blockade with tetraethylammonium bromide (10 mg/kg; -30+/-3 vs. -20+/-3 mmHg, P<0.05) and greater increases in MABP after nitric oxide synthase blockade with NG-nitro-L-arginine (25 mg/kg; 23+/-3 vs. 13+/-2 mmHg, P<0.05) compared with control lambs. By in vitro wire myography, mesenteric and femoral artery microvessel contractile responses to KCl were similar, whereas responses to endothelin (in mesenteric) and norepinephrine (in femoral) were significantly attenuated in Dex lambs compared with controls. Femoral vasodilatory responses to forskolin and sodium nitroprusside were similar in the two groups (n=4). These findings suggest that resetting of the baroreflex, accompanied by increased sympathetic activity and altered nitric oxide-mediated compensatory vasodilatory function, may be important contributors to programming of hypertension.     

Effects of propofol intravenous injection bolus on the left ventricular function and the myocardial beta-adrenoceptor in rats

Propofol bolus injection has been reported to influence cardiovascular functions. However, the detailed mechanism underlying this action has not been elucidated. This study was designed to investigate the effects of propofol i.v. bolus on the left ventricular function, the myocardial beta-adrenoceptor (beta-AR) binding-site density (Bmax) and Kd (apparent dissociation constant) in a 30-minute period. One hundred and four male Wistar rats were randomly divided into four groups: group C (control group), group I (intralipid group), group P1 (5 mg/kg propofol) and group P2 (10 mg/kg propofol). The results showed a significant downregulation of HR, LVSP, +dp/dtmax and -dp/dtmax in both groups P1 and P2 (especially after bolus injection in 7 min) than those of group C (P < 0.05), whereas no significant difference was found between the P1 and P2 groups (P > 0.05). Likely, Bmax was remarkably upregulated in both groups P1 and P2 (P < 0.05, vs. groups C and I), and there was no significant difference between these two groups (P > 0.05). Of note, the Kd value in group P2 (10 mg/kg propofol) was found dramatically increased in 30 min than that in the low-dose propofol-treated group (group P1) as well as in groups C and I (P < 0.05). In conclusion, these results indicate that intravenous injection of propofol bolus can inhibit the cardiac function partially via upregulation of Bmax and downregulation of the beta-AR affinity at higher-dose injection of propofol bolus.