影响急进4010m高原大鼠药代动力学参数的诸因素变化

目的:观察平原Wistar大鼠急进高原后以及急进高原返回平原后,影响其药物代谢动力学参数的诸因素变化。方法:将21只Wistar大鼠随机均分为3组,分别在平原地区(上海55 m)、急进高原(甘肃玛曲4010 m)和急进高原返回平原后,于大鼠眼眶采血分析其主要生化指标,腹主动脉采血进行血气分析,完整摘取脑、肺、肾后进行病理改变的研究。结果:急进高原组与平原组比较pH值、缓冲碱、碱剩余、总二氧化碳含量、动脉血氧饱和度、动脉血氧分压、血清钠离子浓度、乳酸脱氢酶以及总蛋白显著降低(均P<0.05),动脉血二氧化碳分压、血清氯离子浓度、总胆红素以及碱性磷酸酶显著升高(均P<0.05);急进高原返回平原组与平原组相比较pH值、缓冲碱、碱剩余、动脉血氧饱和度、动脉血氧分压、血红蛋白、血清钠离子浓度、乳酸脱氢酶以及总蛋白显著降低,动脉血二氧化碳分压、血清氯离子浓度、丙氨酸氨基转移酶、总胆红素以及尿素显著升高(均P<0.05);急进高原返回平原组与急进高原组比较血红蛋白与碱性磷酸酶显著降低(均P<0.05),总蛋白、总胆红素及尿素显著升高(均P<0.05)。病理结果可见急进高原组与急进高原返回平原组均有不同程度的肺泡壁增厚、充血、水肿,肺泡上皮增生,肺泡间隔增宽,中性粒细胞浸润;大脑神经元细胞水肿并血管周围间隙形成,海马神经元变性,核固缩;肾小球系膜细胞增生。结论:急进高原与急进高原返回平原组大鼠血气指标、生化指标以及心、肝、肾功能均发生明显改变,脑、肺、肾均可见明显病理改变,严重影响药物的药代动力学参数。     

高原低氧大鼠肺组织超微结构及其低氧诱导因子1α的表达

背景：低氧诱导因子1α可介导哺乳动物细胞适应低氧环境。 目的：观察高原低氧对大鼠肺组织超微结构的影响及其低氧诱导因子1α表达变化。 方法：将SD大鼠分别为进行高原低氧干预1,2,3和30 d,并设置对照组。4个高原低氧组由海拔5 m的西安地区途中耗时1 d带到海拔2 700 m的青海格尔木地区、途中耗时2 d带到海拔5 000 m的唐古拉地区,途中耗时3,30 d分别带到海拔4 500 m的西藏那曲地区。 结果与结论：光镜及电镜观察显示,急性高原低氧2 d组肺组织出现明显的高原肺水肿,急性高原低氧30 d组低氧诱导因子1α mRNA的表达明显增高(P < 0.01),高原肺水肿现象则明显减轻。结果证实,低氧习服后肺组织低氧诱导因子1α mRNA表达的提高有利于减轻高原肺水肿。     

模拟高原慢性缺氧环境下便携式氧气机富氧对大鼠行为学的影响

目的:探索模拟高原慢性缺氧环境下便携式氧气机富氧对大鼠行为学的影响。方法:利用低压舱模拟海拔5 000 m高原缺氧环境,利用自主研制的便携式膜法氧气机与大鼠IVC笼盒建立富氧饲养笼。将36只雄性SD大鼠随机分为平原对照组(NC)、缺氧组(HH)与富氧组(HO),HH与HO组置于低压舱内饲养4周(22 h/d),HO组每天有效富氧8h,NC组于舱外同时饲养。实验前及实验后每周监测大鼠体质量,饲养4周后测量各组大鼠行为学指标及皮肤平均血流灌注量数据,进行统计学分析。结果:实验前各组大鼠体质量差异无统计学意义(P0.05),实验后各周HH与HO组体质量均显著低于NC组(P0.01),HH与HO组之间差异无统计学意义(P0.05)。3组大鼠水平自主活动度差异无统计学意义(P0.05);垂直自主活动度HO组较NC和HH组显著提高(P0.05,P0.01),NC与HH组之间差异无统计学意义(P0.05)。皮肤平均血流灌注量HH组与NC和HO组相比显著增加(P0.01),NC与HO组之间差异无统计学意义(P0.05)。结论:模拟海拔5 000 m高原慢性缺氧环境下便携式氧气机富氧能够显著降低大鼠血流灌注量至平原水平,可为大鼠适应更复杂恶劣的高原环境进行血液系统代偿的功能储备;模拟海拔5 000 m高原慢性缺氧环境下便携式氧气机富氧能够显著提升大鼠空间探索与认知能力,对高原缺氧环境下大鼠脑功能具有一定保护与促进作用。     

高原急性缺氧对大鼠食欲及其下丘脑GLP-1 mRNA表达的影响

 目的： 探讨高原急性缺氧对大鼠食欲及其下丘脑胰升血糖素样肽-1 mRNA表达的影响。方法: 雄性Wistar大鼠随机分为平原对照组、3 000 m 缺氧组、4 000 m 缺氧组、5 000 m 缺氧组和 6 000 m 缺氧组，各缺氧组设置缺氧后1、2、3 d 3个时点。观察缺氧环境下大鼠食欲的变化；采用RT-PCR方法检测大鼠下丘脑中GLP-1 mRNA的表达。 结果: ① 高原急性缺氧后，大鼠食欲减退。②对照组和缺氧组大鼠下丘脑中均存在GLP-1 mRNA的表达。高原急性缺氧后，下丘脑GLP-1 mRNA表达增加，并随着海拔高度的上升和缺氧时间的延长逐渐增加 (P<0.05, P<0.01)。结论: 高原急性缺氧后下丘脑GLP-1 mRNA表达增加，可能是大鼠食欲减退的重要原因之一。     

清醒和麻醉状态下豚鼠畸变产物耳声发射检测比较

为了观察豚鼠在麻醉和清醒状态的畸变产物耳声发射 (DPOAE)。我们以 DPOAE幅值和 I/ O曲线作为参数 ,观察清醒和麻醉状态下其参数的变化。结果发现豚鼠在清醒状态下其 DPOAE幅值和 I/ O曲线斜率与正常剂量麻醉状态下相比无显著性差异 (P>0 .0 5 )。我们认为在清醒状态下豚鼠 DPOAE的检测同麻醉状态相比 ,操作简便、结果稳定 ,更接近于生理状态。     

基于磷脂酰肌醇-3激酶/蛋白激酶B/核因子κB通路探讨高原缺氧对大鼠蛛网膜下腔出血后血脑屏障的作用

目的 探讨高原缺氧对大鼠蛛网膜下腔出血(SAH)后血脑屏障的作用及其机制。方法 SPF级健康成年雄性SD大鼠(n=78),随机分为4组：假手术组(sham)、蛛网膜下腔出血模型组(SAH)、高原缺氧假手术组(Hp sham)和高原缺氧蛛网膜下腔出血模型组(Hp SAH)。通过低压模拟舱(海拔5000 m)饲养4 d建立高原缺氧大鼠动物模型，采用颈内动脉刺破法建立SAH大鼠动物模型。SAH后24 h,各组大鼠进行神经功能学评分和出血严重程度评估，Nissl染色和TUNEL染色分别观察大鼠海马组织CA1区神经元形态变化和神经细胞凋亡，Western blotting检测大鼠海马组织磷酸化PI3K(p-PI3K)、PI3K、磷酸化Akt(p-Akt)、Akt、磷酸化核因子κB(p-NF-κB)、 NF-κB及基质金属蛋白酶9(MMP-9)、闭锁蛋白(occludin)、紧密连接蛋白-5(claudin-5)的表达，免疫荧光染色观察大鼠海马组织CA1区occludin、claudin-5蛋白表达。结果 SAH后24 h, SAH组与Sham组、Hp SAH组与Hp Sham组比较，大鼠神经功能...     

急入高海拔环境后对听觉的影响研究

目的 通过模拟高海拔环境对急进入高原人群听力的变化进行研究,并建立动物模型研究急进高原对听觉系统的影响,为急性缺氧引起的耳聋治疗提供理论依据。方法 选择拟急进入高原的受试者,在进入高原前,受试者进入模拟海拔5 000 m的低压氧舱内适应5 h,在入舱前后进行纯音测听(测试频率为250 Hz、500 Hz、1 kHz、2 kHz、4 kHz、8 kHz)。比较受试者入舱前后纯音测听的结果,并进行统计学分析。根据此结果建立动物模型,选取健康雄性C57小鼠50只,将小鼠随机分为对照组、缺氧5 h组、缺氧10 h组、缺氧24 h组、缺氧48 h组,每组10只。低压低氧动物实验舱模拟海拔5 000 m高原环境,采用听觉脑干诱发电位(ABR)测量小鼠听力变化情况。结果 受试者入舱后听力较入舱前有一定变化,双耳听阈及大多数频率(250 Hz、500 Hz、1 kHz、8 kHz)的纯音测听阈值较入舱前升高,差异有统计学意义(P<0.05),右耳中频(2 kHz)纯音测听阈值较入舱前无显著变化(P>0.05)。在动物实验中,实验组Ⅰ、Ⅱ、Ⅲ、Ⅳ波潜伏期较对照组延长(P<0.05),Ⅴ...     

应用大鼠前额叶皮层多通道局部场电位的同步模式研究丙泊酚麻醉程度

目的 研究在清醒、丙泊酚麻醉过程中、翻正反射恢复后3种状态下,大鼠前额叶皮层多通道局部场电位(LFPs)的同步模式,作为界定麻醉程度的客观指标.方法 利用成年SD大鼠5只,在大鼠前额叶皮层植入16通道微电极阵列10 d后,应用Cerebus多通道信号采集分析系统,记录大鼠在清醒、丙泊酚麻醉过程中、翻正反射恢复后3种状态下前额叶皮层的16通道信号.丙泊酚麻醉按0.1 mg/(kg体重·min)的剂量,恒速静脉输注.对记录的原始信号进行预处理,获取LFPs,应用Hilbert变换计算LFPs相位系列.选择参考通道,分别计算3种状态下4s时间段内其它15通道LFPs相位与参考通道LFPs相位的相关动态值,计算窗口200 ms,窗口移动步长50 ms.结果 大鼠在清醒状态下LFPs相位的相关动态值比在丙泊酚麻醉状态下小(P<0.05);恢复翻正反射后的LFPs相位相关动态值比清醒状态大(P<0.05),比麻醉状态下小(P<0.05).结论 大鼠在清醒状态下,其前额叶皮层LFPs相位未呈现同步性;在丙泊酚麻醉状态下,呈现高度的同步性;在麻醉复苏期间,同步性在2者之间.多通道LFPs相位的同步程度可以界定不同的麻醉程度.     

应用大鼠前额叶皮层多通道局部场电位的同步模式研究丙泊酚麻醉程度

目的 研究在清醒、丙泊酚麻醉过程中、翻正反射恢复后3种状态下,大鼠前额叶皮层多通道局部场电位(LFPs)的同步模式,作为界定麻醉程度的客观指标.方法 利用成年SD大鼠5只,在大鼠前额叶皮层植入16通道微电极阵列10 d后,应用Cerebus多通道信号采集分析系统,记录大鼠在清醒、丙泊酚麻醉过程中、翻正反射恢复后3种状态下前额叶皮层的16通道信号.丙泊酚麻醉按0.1 mg/(kg体重·min)的剂量,恒速静脉输注.对记录的原始信号进行预处理,获取LFPs,应用Hilbert变换计算LFPs相位系列.选择参考通道,分别计算3种状态下4s时间段内其它15通道LFPs相位与参考通道LFPs相位的相关动态值,计算窗口200 ms,窗口移动步长50 ms.结果 大鼠在清醒状态下LFPs相位的相关动态值比在丙泊酚麻醉状态下小(P<0.05);恢复翻正反射后的LFPs相位相关动态值比清醒状态大(P<0.05),比麻醉状态下小(P<0.05).结论 大鼠在清醒状态下,其前额叶皮层LFPs相位未呈现同步性;在丙泊酚麻醉状态下,呈现高度的同步性;在麻醉复苏期间,同步性在2者之间.多通道LFPs相位的同步程度可以界定不同的麻醉程度.     

高原低氧对大鼠心肺组织超微结构的影响

背景：研究表明快速进入高原地区时,机体不可避免地会受到不同程度的损伤,以心肺损伤较显著。 目的：观察低氧习服对高原低氧大鼠心肺组织的超微结构影响。 方法：将SD大鼠分别为进行高原低氧干预1,3和30 d,并设置对照组。3个高原低氧组由海拔5 m的西安途中耗时1 d带到海拔2 700 m的青海格尔木地区、途中耗时3,30 d分别带到海拔4 500 m的西藏那曲地区,观察各时间点心肺标本的组织学变化。 结果与结论：急性高原低氧1,3 d组肺组织显微和超微结构出现明显的间质性肺水肿和肺泡性肺水肿,其心脏组织光镜下大鼠各室壁心肌细胞均可见不同程度的浊肿、空泡变性、溶解坏死及间质水肿等,电镜下可见心肌细胞线粒体肿胀,肌浆网扩张,肌原纤维溶解,细胞内外水肿等,急性高原低氧3 d上述改变右室壁较左室壁明显,而低氧习服后高原低氧30 d组间质性水肿和则肺水肿明显减轻。结果证实,高原急性缺氧可造成大鼠间质性肺水肿和肺泡型肺水肿,并引起以右心室为主的全心性损伤,经过高原低氧习服后心肺组织病变明显减轻。     

颈淋巴引流阻滞对清醒自由活动大鼠的血压的影响

 目的：观察颈淋巴引流阻滞（CLB）对清醒自由活动大鼠的血压的影响，并初步探讨其机制。 方法： 采用SD大鼠，随机分为假手术组（Sham组）和CLB组。应用监测清醒自由活动大鼠血流动力学变化的手段，分别连续记录两组大鼠在假手术和CLB手术术前及术后第1、3、7、11、15 d收缩压（SBP）、舒张压（DBP）、心率（HR）的变化。测定两组大鼠术前、术后第1、7及15 d压力感受性反射敏感性（BRS）。脱机分析其相应的血压波动性（BPV）、心率变异性（HRV）。 结果： CLB术后第1天SBP、DBP、MAP、HR及BRS下降，第7天降至最低，BRS在7 d后无明显恢复，而血压及心率随着CLB时间的延长呈先下降后上升。相反，HRV、BPV先上升后下降。 结论： CLB可导致清醒自由活动大鼠血压降低，心血管系统神经调节功能下降。     

Changes in sympathetic nerve activity during morphine abstinence in the rat

The aim of the study was to examine sympathetic nerve activity, heart rate and blood pressure during naloxone-precipitated withdrawal reactions in morphine-dependent rats. In two groups of rats, one group conscious and the other anaesthetized with chloralose, renal sympathetic nerve activity (rSNA), heart rate (HR) and mean arterial blood pressure (MAP) were recorded before and during naloxone-precipitated abstinence. The conscious rats showed a biphasic pattern in the withdrawal responses. Initially, after small doses of naloxone, rSNA and HR increased and increased somatomotor activity including 'wet-dog' shakes were observed. However, upon further administration of naloxone, rSNA and HR promptly decreased while MAP increased. As rSNA was lowered, the withdrawal behaviour of the rats was markedly diminished and the animals rested calmly in the cages. In contrast, the anaesthetized group reacted with an immediate decrease in rSNA after the lowest dose of naloxone, followed by an increase in MAP and HR after higher doses of naloxone, although rSNA was still decreased. In both groups, rSNA remained below pre-naloxone control levels when the increased MAP was lowered to the pre-naloxone level with sodium nitroprusside, indicating a central origin of the sympathetic inhibition. It is concluded that naloxone elicits a biphasic rSNA response in the conscious, morphine-dependent rat. This includes an initial increase upon low naloxone doses followed by a pronounced inhibition of rSNA after higher doses. In chloralose-anaesthetized rats, rSNA declined already after low doses of naloxone. It is suggested that there might be a tonic, excitatory input on rSNA, mediated by the activation of opiate receptors by high levels of circulating morphine in the addicted animal. Naloxone will therefore decrease the tonic sympathetic nerve activity in these rats.     

Cardiovascular and intravesical pressure responses during natural micturition in conscious rats

Urinary bladder distension is known to influence the cardiovascular system under a pathophysiological condition such as spinal cord injury, hypertension, and arteriosclerosis. A reflex due to bladder distension and/or contraction is considered as one reason for the cardiovascular disturbance associated with micturition. However, it has remained unknown how much intravesical pressure (IVP) rises during micturition in daily life and to what extent mean arterial blood pressure (MAP) and heart rate (HR) respond at that time. To answer these questions, we attempted to examine the direct changes in IVP, MAP, and HR during natural micturition in freely moving conscious rats. IVP increased from the baseline value of 4 +/- 0.2 mmHg to 14 +/- 0.5 mmHg during natural micturition. Although MAP and HR began to increase before micturition, the increases in MAP and HR became significant 1-4 s before its onset. The peak increases in MAP and HR (7 +/- 0.8 mmHg and 14 +/- 3 beats/min, respectively) were delayed by 2 s from the peak IVP. Following an administration of xylocaine into the urinary bladder, the increases in MAP and HR during micturition were significantly blunted to 5 +/- 2 mmHg and 8 +/- 3 beats/min, although IVP increased the same as it did during micturition without xylocaine. Moreover, the relationship between IVP and MAP or HR during natural micturition resembled that between IVP and the vesico-cardiovascular reflex responses during isovolumic bladder contraction in anesthetized rats. Therefore it is concluded that natural micturition in freely moving conscious rats accompanies the significant cardiovascular responses despite a limited increase in intravesical pressure, to which a reflex from the urinary bladder may substantially contribute.     

Cardiovascular effects produced by activation of GABA receptors in the rostral ventrolateral medulla of conscious rats

The rostral ventrolateral medulla (RVLM) has been proposed as a region playing a major role in the tonic and reflex control of sympathetic vasomotor activity and blood pressure. Pharmacological activation of GABA(A) receptors with muscimol in the RVLM of anesthetized rats results in a large fall in mean arterial pressure (MAP), heart rate (HR) and sympathetic activity. In this study we evaluated the effects of activation of GABA receptors in the RVLM of conscious, freely moving rats. Bilateral microinjections of muscimol into the RVLM of conscious rats produced a large fall in MAP (-38+/-4 mm Hg, n=7) when compared with saline injections (NaCl 0.9%, 7+/-1 mm Hg, n=4). The decrease in MAP evoked by muscimol was accompanied by a significant increase in HR (muscimol 69+/-13 bpm vs. vehicle -33+/-12 bpm, P<0.05), an effect that was completely abolished by beta1 adrenergic receptor blockade. Conversely, bilateral microinjections of GABA(B) agonist, baclofen, evoked a pressor response, but in this case, the increase was not significantly different from that evoked by vehicle injections. These results 1) indicate that GABA(A) receptors have a powerful influence on the resting activity of RVLM neurons in conscious rats; 2) indicate that a compensatory sympathetic-mediated tachycardia is present after inhibition of RVLM neurons in conscious rats; 3) confirm and extend previous findings showing that RVLM neurons are critical for blood pressure maintenance even in normal non-anesthetized conditions.     

Intrathecal kynurenate reduces arterial pressure, heart rate and baroreceptor-heart rate reflex in conscious rats

In the present study, an excitatory amino acid (EAA) pathway in the spinal cord which maintains sympathetic vasomotor tone in conscious rats has been investigated. To this end, the cardiovascular effects of an intrathecally administered EAA antagonist, kynurenate (KYN), were studied in conscious rats. KYN (0.5 mumol in 10 microliters) caused a dramatic reduction in mean arterial pressure (MAP) and heart rate (HR) that persisted for 2-3 h, and also resulted in extensor paralysis of the hindlimbs. The time courses of fall in MAP and HR and hindlimb paralysis were similar. Baroreceptor-HR reflex activity was also markedly impaired after KYN, suggesting functional diminution of sympathetic outflow at the level of the spinal cord after blockade of EAA receptors by KYN. Xanthurenate, a metabolite of KYN without EAA antagonistic properties, produced negligible effects at the same dose of KYN. While these findings do not identify the putative EAA pathway, they do provide the first demonstration that this system is tonically active in conscious rats.     

Involvement of the paraventricular nucleus (PVN) of hypothalamus in the cardiovascular alterations to head up tilt in conscious rats

We evaluated the involvement of paraventricular nucleus (PVN) in the changes in mean arterial pressure (MAP) and heart rate (HR) during an orthostatic challenge (head up tilt, HUT). Adult male Wistar rats, instrumented with guide cannulas to PVN and artery and vein catheters were submitted to MAP and HR recording in conscious state and induction of HUT. The HUT induced an increase in MAP and HR and the pretreatment with prazosin and atenolol blocked these effects. After inhibition of neurotransmission with cobalt chloride (1 mM/100 nl) into the PVN the HR parameters did not change, however we observed a decrease in MAP during HUT. Our data suggest the involvement of PVN in the brain circuitry involved in cardiovascular adjustment during orthostatic challenges.     

Effects of centrally administered losartan on deoxycorticosterone-salt hypertension rats

To investigate whether brain AT1 receptor stimulation contributes as a hypertensive mechanism to deoxycorticosterone acetate (DOCA)-salt hypertension, losartan (1 mg/4 microL) or artificial cerebrospinal fluid (aCSF) was injected into the lateral cerebral ventricle in conscious control uninephrectomized Wistar rats or rats with DOCA-salt for 2 or 4 weeks, and mean arterial pressure (MAP) and heart rates (HR) were recorded. In rats with DOCA-salt treatment, resting MAP increased to 144+/-6 mmHg after 2 weeks and to 170+/-5 mmHg after 4 weeks versus 115- 120 mmHg in controls. In rats with 2 week DOCA-salt treatment, MAP started declining at 4 hr after intracerebroventricular (icv) injection of losartan, and significant decreases in MAP were found at 18 and 24 hr. In rats with 4 week DOCA-salt treatment, MAP was significantly decreased at 4, 18 and 24 hr. In both groups MAP decreased to that of control rats. In control rats, icv losartan had no effect on MAP and HR. Icv aCSF did not significantly change MAP and HR in either DOCA-salt hypertensive rats or control rats. Normalization of MAP after icv administration of the AT1 receptor antagonist suggests a significant role for brain AT1 receptor stimulation in the development and maintenance of hypertension in the DOCA-salt hypertensive rat model.     

Spontaneous variations in arterial blood pressure, heart rate and sympathetic nerve activity in conscious normotensive and spontaneously hypertensive rats

In the present study we have recorded spontaneous variations in mean arterial blood pressure (MAP), heart rate (HR) and mean rectified splanchnic nerve activity (SNA) in conscious undisturbed normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The variability in blood pressure was not significantly different but HR variability tended to be lower in SHR. The variability in SNA expressed as % change from mean value was not significantly different between SHR and WKY. By computer techniques the correlation between HR, MAP and SNA could be calculated during spontaneous variations of these parameters. The slope of the regression line correlating HR and SNA was significantly steeper in SHR than in WKY (0.73, 0.47 resp.). Thus a certain change in HR was associated by a greater change in SNA in SHR compared with WKY. Spontaneous changes in SNA could be divided in principally two different patterns. One typical pattern was a rise in SNA in parallel with a drop in MAP. This pattern was most likely triggered by the arterial baroreceptors and was called a "baroreceptor-pattern". Marked spontaneous excitations in SNA and HR was also observed during natural behaviours such as eating, drinking and explorative behaviour, a so called "centrally mediated pattern".     

Central haemodynamics during morphine abstinence in anaesthetized rats

Central haemodynamics were studied in one group of morphine-dependent rats, and in a non-dependent control group. before and after administration of repeated bolus doses of naloxone. Dependence was induced by s.c. morphine pellet implantations. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO) and mean transit time (MTT) were measured in the conscious state, after induction of chloralose anaesthesia and after the administration of naloxone (0.005, 0.05, 0.5 and5 mg kg 1 i.v.). Total peripheral resistance (TPR), stroke volume (SV) and central blood volume (CBV) were subsequently calculated. The haemodynamic variables did not differ significantly in the conscious state, except for a lower SV, when compared with the non-dependent control group. However, in response to anaesthesia the dependent rats exhibited a greater fall in MAP, mainly due to a TPR decrease. Naloxone elicited a marked increase in MAP in the morphine-dependent group, which was mainly caused by an increase in TPR. Naloxone induced no significant change compared with the control group in CO and CBV, while SV increased concomitantly with a lowered HR after naloxone in the morphine-dependent group. These results suggest that the withdrawal hypertension during morphine abstinence was mainly explained by an increase in TPR, reflecting an augmented tone of the resistance vessels. The minor changes in CBV indicate that the tone of the venous capacitance vessels was largely unaffected by naloxone-induced morphine abstinence.     

Differential haemodynamic effects of atrial natriuretic peptide (ANP) in normotensive and spontaneously hypertensive rats

Central haemodynamic parameters and cardiac performance were measured in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) control rats after a 10-min infusion of rat ANP (103-125), 1 micrograms kg-1 min-1. Mean Arterial blood pressure (MAP) decreased by approximately 10% in both groups of rats. Heart rate (HR) increased slightly in both strains during the infusion. In the normotensive group the fall in MAP was due to a reduction in cardiac output (CO) while in the SHR there was a decrease in CO as well as in total peripheral resistance (TPR). The ANP infusion also reduced central blood volume (CBV) and stroke volume (SV) in both groups of rats. The reduction in CBV and CO was significantly more pronounced in the WKY strain. Left ventricular end diastolic pressure (LVEDP) and cardiac contractility (dP/dt) did not change while central venous pressure (CVP) was slightly decreased in the WKY group as a result of the ANP infusion. We conclude that ANP reduces MAP in normotensive animals by a reduction in CO. In the SHR a reduction in TPR also contributes to the fall in MAP. Atrial natriuretic peptide did not exert any negative inotropic effects, but the reduction of CO was due to an increased venous compliance.