Endogenous vasopressin and baroreflex mechanisms

This article reviews the anatomical and functional evidence for ascending pathways from specific brain regions to the PVN and SON which could influence AVP release. The majority of evidence favours the main projection being from a region in the caudal VLM which may coincide with the noradrenergic neurons of the A₁ cell group. However, the transmitter(s) involved have yet to be identified, and whether the pathway is excitatory and/or inhibitory remains to be fully resolved.Anatomical and functional evidence is reviewed for descending projections from the SON and PVN to specific brain regions involved in cardiovascular control, and their possible involvement in baroreflex mechanisms is discussed. However, there is little unequivocal evidence that AVP is the main neurotransmitter utilized by descending projections from PVN to NTS and DMX. While, in some situations, circulating endogenous AVP exerts cardiovascular effects, details of its putative influences on baroreflex mechanisms are lacking.     

Immunocytochemical distribution of met-enkephalin-Arg6-Gly7-Leu8 in the rat lower brainstem

The distribution of methionine-enkephalin-Arg6-Gly7-Leu8, a unique peptide derived from proenkephalin A in the rat brainstem, was studied immunocytochemically by using a highly specific antiserum to this octapeptide sequence. Immunoreactive perikarya with various shapes and sizes were detected in many regions of the rat brainstem. Dense accumulation of immunoreactive perikarya and fibers was seen in the nuclei associated with special sensory and visceral functions, such as the interpeduncular nucleus, the parabrachial nucleus, the nucleus of the solitary tract, and the nucleus of the spinal tract of the trigeminal nerve. Clusters of methionine-enkephalin-Arg6-Gly7-Leu8-like immunoreactive perikarya and fibers were observed in certain areas considered to play a role in nociception and analgesia, such as the central gray of the midbrain central gray and the raphe magnus nucleus. Some methionine-enkephalin-Arg6-Gly7-Leu8-like immunoreactive perikarya were distributed in the lateral reticular nucleus, the nucleus of the solitary tract, and the raphe magnus nucleus, where monoaminergic neurons were also detected. In addition to the previously reported enkephalinergic cells, we found many methionine-enkephalin-Arg6-Gly7-Leu8 containing neurons; the rostral and caudal linear nucleus of raphe, the median raphe nucleus, entire length of the raphe magnus nucleus, the medial longitudinal fasciculus, the cuneate nucleus, the external cuneate nucleus, the gracile nucleus, and the area postrema. The wide distribution of this octapeptide-like immunoreactivity reflected neurons expressing the preproenkephalin A gene distributed more widely than previously reported and that innervated many regions.     

ROLE OF NITRIC OXIDE IN THE CONTROL OF THE RENAL MEDULLARY CIRCULATION

1. Nitric oxide (NO) has been implicated as an important controller in the short- and long-term regulation of arterial pressure. Studies performed in our laboratory have demonstrated that chronic intravenous administration of the NO synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME) selectively decreases renal medullary blood flow, causes sodium and water retention and leads to hypertension. 2. To determine the importance of the renal medullary effects in this model of hypertension, further studies were conducted to examine the influence of selective stimulation or inhibition of renal medullary NO on whole kidney function and cardiovascular homeostasis. With the use of a unique catheter to directly infuse into the renal medullary interstitial space, stimulation (bradykinin or acetylcholine) or inhibition (L-NAME) of renal medullary NO selectively increased or decreased renal medullary blood flow. 3. The changes in medullary flow in these experiments were associated with parallel changes in sodium and water excretion independent of alterations in renal cortical blood flow or glomerular filtration rate. 4. Studies were then undertaken to examine the long-term effects of selective NO inhibition in the renal medulla on cardiovascular homeostasis. Chronic infusion of L-NAME directly into the renal medullary interstitial space of uninephrectomized Sprague-Dawley rats led to a selective decrease in renal medullary blood flow that was sustained throughout the 5 day L-NAME infusion period. The decrease in medullary blood flow was associated with retention of sodium and the development of hypertension and the effects were reversible. 5. The data reviewed indicate that NO in the renal medulla has a powerful influence on fluid and electrolyte homeostasis and the control of blood pressure.     

THE INCREASE OF FEMORAL ARTERIAL FLOW BY STIMULATING THE DORSAL AND VENTRAL MEDULLA IN CATS

1. In chloralose-urethane anaesthetized cats, the dorsal cardiovascular reactive area (DCRA) in the parvocellular reticular nucleus dorsomedial to the facial nucleus, and the ventral cardiovascular reactive area (VCRA) ventromedial to the facial nucleus, were stimulated by microinjections of sodium glutamate (100–200 nmol) or electric current. 2. Stimulation of DCRA, with a long latency of 15–20 s, elicited a marked increase of blood flow in the contralateral femoral artery with little change to moderate increase in systemic arterial blood pressure (ABP). In the relatively dorsal portion of DCRA, however, a smaller increase of blood flow in the ipsilateral femoral artery was elicited. 3. On the other hand, stimulation of VCRA with a short latency (3–5 s) evoked an increase of blood flow in both femoral arteries which was more prominent on the contralateral side. The responses were accompanied with decreases in the blood flow of other vascular beds with only a slight increase or minimal change in ABP. 4. The data suggest that DCRA and VCRA are both viscerotopically organized to alter the resistance of individual vascular beds for redistribution of blood flow.     

Effects of MPP+ on catecholamine levels in adrenal glands and heart of rats

The effects of MPP⁺ (2.5–20 mg/kg) on the adrenal glands and heart were investigated in rats. At various periods after s.c. drug administration the rats were decapitated and tissue catecholamine levels were determined by means of HPLC with electrochemical detection. Adrenal dopamine (DA) levels were reduced at 2–8 h after MPP⁺ administration, but this decrease was followed by an elevation after 16 h and return to the control values after one week. Three successive injections of MPP⁺ caused a statistically significant elevation in adrenal DA, one day, with a tendency to elevation four and seven days after the last injection, whereas a severe (up to 96%) decrease in heart noradrenaline (NA) was found one day after the last injection. Seven days after the last injection a 50% depletion of NA in the heart was still observed. Pretreatment with GBR 12909 (30 mg/kg, 4 h) blocked the MPP⁺ (10 mg/kg, 2 h) induced reduction of adrenal DA levels, but at the same time GBR 12909 failed to block the effects of MPP⁺ in the heart. One day after three successive daily injections of MPP⁺ (10 mg/kg each), the DA-uptake inhibitor GBR 12909 (30 mg/kg, 6 h) could still induce an increase in adrenal DA.MPP⁺ appears to lack persistent cytotoxic action in the adrenal medulla but rather to cause a transient inhibition of DA synthesis followed by a compensatory stimulation. The inhibition can be blocked by specific inhibitor of the DA-uptake mechanism, suggesting a direct effect of MPP⁺ taken up by adrenomedullary cells. The data obtained so far do not suggest any involvement of peripheral dopaminergic nerves in the action of MPP⁺ on the adrenal medulla. The long-lasting depletion of the heart NA, however, suggests a lesion of peripheral noradrenergic nerves.Part of this work was presented at 6th International Symposium on Chromaffin Cell Biology, Marburg, Germany, 18–23 August 1991 Correspondence to: M. Kujacic at the above address     

Addition of sufentanil to bupivacaine in caudal block effect on stress responses in children

BACKGROUND: The aim of the present randomized study was to determine the effect of adding sufentanil to bupivacaine, compared with bupivacaine alone in caudal block, on the surgical stress response in children. METHODS: The children were premedicated with midazolam 0.5 mg/kg. All children received induction with nitrous oxide and sevoflurane. Anesthesia was maintained with the same volatile agents in the both groups. The children were randomly allocated to two groups. Group I received bupivacaine alone (n = 17) and group II received bupivacaine + sufentanil (n = 16). Caudal block was performed with 0.25% bupivacaine 2 mg/kg (group I) or 0.25% bupivacaine 2 mg/kg with sufentanil 0.5 microg/kg (group II) after induction of anesthesia. Blood samples were obtained after induction of anesthesia (T(0)) to measure baseline concentrations of cortisol, prolactin, glucose and insulin. Additional samples were obtained 30 min after the start of surgery (T(1)), and 60 min after the end of surgery (T(2)). RESULTS: All of the basal values (T(0)) were within the normal ranges of the authors' laboratory for children of this age group and there were no differences between the groups (P > 0.05). In both groups, glucose concentration increased at T(1), compared with T(0) and T(2) (P < 0.05). The glucose concentration was unchanged at T(2) compared with T(0) in both group (P > 0.05). In both groups, prolactin concentration increased at T(1), compared with T(0) and decreased at T(2), compared with T(1) (P < 0.05). Cortisol decreased at T(1) and T(2), compared with T(0) in both groups. (P < 0.05). Insulin concentration remained unchanged at T(0) and T(2), but increased slightly at T(1) in both groups (P > 0.05). There were no significant differences in plasma prolactin, cortisol, glucose and insulin levels between the two groups at T(1) and T(2) (P > 0.05). CONCLUSION: There is no advantage in adding 0.5 microg/kg sufentanil to bupivacaine over bupivacaine alone in the caudal block, with regard to the surgical stress response in children.     

Effect of Central Muscarine Receptor Blockade with DKJ-21 on the Blood Pressure and Heart Rate in Stress-Induced Hypertensive Rats

Da-Nian Zhu, Long-Mei Xue, Peng Li. Effect of central muscarine receptor blockade. with DKJ-21 on the blood pressure and heart rote in stress-induced hypertensive rats.

The experiments were performed on Wistar or Sprague-Dawley rats of both sexes divided at random into stress and control groups. The rats in the stress groups were put into cages and subjected to electric foot-shocks and noises for 9-15 days, which caused an increase in blood pressure (BP) and heart rate (HR). In hypertensive rats DKJ-21 (4mg/lml) was injected intravenously (i.v.), and 0.5-1.0h after administration the BP and HR dropped from the high level to normotensive level. In normotensive rats, however, administration of DKJ-21 had no effect on BP or HR. In separate groups of normotensive rats, pretreatment of DKJ-21 (4 mg/l ml, i.v.) blocked the pressor and tachycardiac effect induced by microinjection of physostigmine (0.4μg/0.1 /μl/site), corticosterone (40μg/0.1μl/site) or aldosterone (40 μg/0.1 μl/site) into the rostral ventrolateral medulla (rVLM). Furthermore, DKJ-21 also attenuated the enhancement of the pressor response to stimulation of the defense area in the midbrain, which was induced by microinjection of drugs (mentioned above) into the rVLM. These results indicate that i.v. DKJ-21 can selectively block the muscarinic receptors in the rVLM in stress-induced hypertensive rats, which suggests that abnormal enhancement of cholinergic mechanism in the rVLM may be related to hypertensive effects of corticoids in this area.     

INVOLVEMENT OF NON-NMDA AND NMDA RECEPTORS IN GLUTAMATE-INDUCED PRESSOR OR DEPRESSOR RESPONSES OF THE PONS AND MEDULLA

1. Fifty-five intact and six baroreceptor denervated and vagotomized cats of either sex were anaesthetized intraperito-neally with urethane (400 mg/kg) and a-chloralose (40 mg/kg). Responses of the systemic arterial pressure (SAP), mean SAP (MSAP) and sympathetic vertebral nerve (VNA) and renal nerve activities (RNA) were recorded. 2. In intact animals, monosodium L-glutamate (Glu, 0.1 mol/L, 50 nL) was microinjected into pressor areas of the locus coeruleus (LC), gigantocellular tegmental field (GTF), rostral ventrolateral medulla (RVLM) and dorsomedial medulla (DM), and the depressor areas of caudal ventrolateral medulla (CVLM). The induced actions were compared before and after microinjection of either glutamate antagonists, glutamate diethylester (GDEE, 0.5 mol/L, 50–100nL), a competitive AMPA receptor blocker, or 2-amino-5-phosphonovaleric acid (D-AP5, 0.025 mol/L, 50–100 nL), a competitive N-methyl-D-aspartate (NMDA) receptor blocker. GDEE completely blocked the increases of SAP and VNA elicited from all pressor areas. D-AP5 only partially blocked the pressor but slightly blocked VNA and RNA responses from LC, GTF and DM, particularly those from RVLM. Neither GDEE nor D-AP5 blocked the depressor responses of SAP and two nerve activities elicited from CVLM. 3. In baroreceptor denervated animals, NMDA (2 mmol/L, 50–100 nL) and AMPA (0.2 mmol/L, 50–100 nL) were micro-injected into the same pressor areas of GTF, RVLM and DM and the depressor area of CVLM responsive to Glu activation (0.1 mol/L, 30 nL). In RVLM, DM and CVLM, the results of either NMDA or AMPA were similar to those induced by Glu. However, in GTF, microinjection of either NMDA or AMPA did not induce similar responses to Glu. This suggests that the nature of GTF may differ from RVLM and DM. 4. The above results suggest that the Glu-induced pressor responses from LC, GTF, DM and especially RVLM, are primarily mediated through AMPA receptors. The Glu-induced depressor responses from CVLM may not be predominantly mediated by either AMPA or NMDA receptors. 5. In both baroreceptor-intact and -denervated cats stimulation of the pressor areas often produced an increase of VNA and a decrease of RNA, while in the depressor CVLM decreased both VNA and RNA. The VNA, but not RNA were positively correlated with the pressor responses, while both VNA and RNA were positively correlated with the depressor responses. This may suggest that neurons of the sympathetic vertebral and renal nerves are topographically organized in the brain.     

猫延髓嘴侧腹外侧区微量注射内皮素－1对心血管和肾交感神经活动的影响

采用脑立体定向和脑内微量注射技术研究了猫延髓嘴侧腹外侧区（ｒＶＬＭ）微量注射内皮素－１（ＥＴ－１），对平均动脉压（ＭＡＰ）、心率（ＨＲ）和肾交感神经活动（ＲＮＡ）的影响。结果表明：ｒＶＬＭ内微量注射ＥＴ－１（２ｐｍｏｌ，０．５μｌ），可显著升高平均动脉压、增加心率和增强肾交感神经活动，并存在量－效间的正相关关系。双侧颈部迷走神经切断后，不影响上述结果。静脉预先给与α－受体阻断剂（Ｒｅｇｉｔｉｎｅ，５ｍｇ／ｋｇ），能显著抑制ＥＴ－１的上述升压作用。放射免疫观察到，ｒＶＬＭ内微量注射ＥＴ－１后，血浆精氨酸升压素（ＡＶＰ）含量显著升高，其变化与血压变化呈显著一致。以上结果提示，（１）ｒＶＬＭ内ＥＴ－１参与心血管活动的中枢调节，并显示有部位特异性；（２）该调节作用主要通过改变交感神经传出活动实现，而与迷走神经活动无关；（３）ｒＶＬＭ内ＥＴ－１还可能激动下丘脑室旁核及视上核的升压素能神经元，从而参与心血管活动的调节。     

大鼠延髓腹外侧区在可乐定心血管效应中的作用

目的：探讨大鼠延髓腹外侧区（VLM）在介导可乐定心血管效应中的作用。方法：氨基甲酸乙酯麻醉SD大鼠，应用微量注射和细胞外记录等方法观察尾端延髓腹外侧区（CVLM）和头端延髓腹外侧区（RVLM）内局部给予可乐定导致的心血管活动变化。结果：单侧CVLM微量注射可乐定（5nmol/100nl,n=10)不仅能明显升主动脉血压（AP）和增加心率（HR）（P＜0．01），而且能增加同侧RVLM压力敏感性神经元（n=80)的放电频率（P＜0．01），而单侧RVLM微量注射可乐定（5nmol/100nl,n=9)，明显降低AP和HR（P＜0．01）。结论：RVLM和CVLM在介导可乐定的心血管效应中具有不同的作用。