Effect of verapamil on the cerebral circulation

In acute experiments on anesthetized cats verapamil (0.05, 0.1 and 0.5–1 mg/kg, intravenously) lowered the tone of the cerebral vessels and the systemic arterial pressure. Changes in the volume velocity of the cerebral blood flow were phasic in character depending on the tone of the cerebral vessels and the blood pressure level; the blood flow in the cerebral cortex increased more than in the reticular formation. pO₂ in the cerebral cortex correlated with the blood flow. The diameter of the pial arteries increased both after intravascular injection of verapamil and after its local application. Blockade of the -adrenoreceptors, muscarinic cholinoreceptors, and histamine receptors and preliminary injection of a sympatholytic did not ablish the vasodilator effect of verapamil. It is suggested that the vasodilatation is myotropic in character and possibly connected with electrolyte metabolism.Department of Pharmacology, Pyatigorsk Pharmaceutic Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 4, pp. 434–436, April, 1978.     

Effect of ornid on regulation of the cerebral circulation

An investigation by radioisotope, electromagnetic, and resistographic methods showed that Ornid reduces the cerebral blood flow. At the same time it completely inhibits constrictor reactions of the cerebral vessels to stimulation of sympathetic and somatic nerves. Ornid also has a protective action against experimental disturbances of the cerebral circulation of adrenergic nature.Laboratory of Pharmacology of the Nervous System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 5, pp. 427–429, May 1979.     

高血压鼠脑底动脉血管活性肠多肽能神经与神经节的关系

目的:探讨脑底动脉血管活性肠多肽能神经在高血压的发生和发展中的作用.方法:应用免疫组织化学ABC法和神经节切除术,观察了高血压鼠脑底动脉血管活性肠多肽能神经纤维与蝶腭神经节和耳神经节的关系.结果:手术Ⅰ组作一侧蝶腭神经节切除术,双侧脑底动脉壁上的阳性纤维明显减少;Ⅱ组作一侧耳神经节切除术,双侧大脑后动脉和基底动脉壁上的阳性纤维密度减少;Ⅲ组作一侧颈上神经节切除术,基底动脉的阳性纤维减少.结论:自发性高血压鼠一侧脑底动脉的血管活性肠多肽能神经纤维主要起源于双侧蝶腭神经节,部分起源于耳神经节和颈上神经节.提示血管活性肠多肽能神经可能在高血压的发生和发展方面起着重要的作用.     

Effect of sodium hydroxybutyrate on the cerebral circulation and regional vasomotor reflexes

Experiments on cats in which electromagnetic and resistographic methods were used showed that sodium hydroxybutyrate (100 mg/kg) considerably increases the cerebral circulation. It also increases the blood flow into the brain during the period of formation of pressor blood pressure reflexes. An increase in blood flow also is observed in the system of the femoral arteries, whereas in the intestinal artery, on the other hand, the increase in the blood flow is reduced during vasomotor reflexes. Reflex changes in the resistance of the regional vessels also differ in character: depression of pressor reflexes in the cerebral vessels accompanied by facilitation in the intestinal and femoral arteries and potentiation of the dilator phase of the reflex in the limb vessels. These differences are evidently based on differences in the sensitivity of sympathetic formations in the central components of the different regional vasomotor reflexes to hydroxybutyrate.Laboratory of Pharmacology of the Nervous System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 11, pp. 555–557, November, 1979.     

Effect of serotonin on respiration,cerebral circulation,and blood pressure in rats

The effects of intravenous serotonin on respiration, cerebral circulation, and blood pressure were examined in narcotized rats. Serotonin rapidly decreased local cerebral blood flow (by almost 30%) and blood pressure. Hemodynamic phenomena were accompanied by sharp changes in the respiration pattern: short-term apnea in all cases. The mechanism of this apnea was related to initial stages in blood pressure changes and had a neurogenic nature.__________This revised version was published online in July 2005 with the addition of the issue titleTranslated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 1, pp. 72–76, January, 2005     

Overall distribution of vasoactive intestinal polypeptide-containing nerves on the wall of cerebral arteries: an immunohistochemical study using whole-mounts

The overall distribution of vasoactive intestinal polypeptide (VIP)-like immunoreactivity on the wall of the cerebral arteries, including its 3-dimensional profile, was investigated by means of the indirect immunofluorescence method using flat-mounts. VIP-immunoreactive fibers run spirally on the wall of the cerebral arteries. On the wall of the large arteries, such as the vertebral artery, basilar artery, internal carotid artery, within and/or without the circle of Willis, posterior and anterior communicating arteries, proximal parts of anterior, mid and posterior cerebral arteries, these fibers are richly distributed and show a dense grid-like appearance. The highest density was identified on the wall of the anterior cerebral artery, internal carotid artery and anterior communicating artery, while the lowest density was on the posterior communicating artery. On the other hand, on the walls of the branches of these arteries or along distal parts of the anterior, mid and posterior cerebral arteries, the number of VIP-immunoreactive fibers decreased markedly.     

Focal,but not global,cerebral ischaemia causes loss of myenteric neurons and upregulation of vasoactive intestinal peptide in mouse ileum

Reduced blood flow to the brain induces cerebral ischaemia, potentially causing central injury and peripheral complications including gastrointestinal (GI) dysfunction. The pathophysiology behind GI symptoms is suspected to be neuropathy in the enteric nervous system (ENS), which is essential in regulating GI function. This study investigates if enteric neuropathy occurs after cerebral ischaemia, by analysing neuronal survival and relative numbers of vasoactive intestinal peptide (VIP) and neuronal nitric oxide synthase (nNOS) expressing neurons in mouse ileum after three types of cerebral ischaemia. Focal cerebral ischaemia, modelled by permanent middle cerebral artery occlusion (pMCAO) and global cerebral ischaemia, modelled with either transient occlusion of both common carotid arteries followed by reperfusion (GCIR) or chronic cerebral hypoperfusion (CCH) was performed on C56BL/6 mice. Sham‐operated mice for each ischaemia model served as control. Ileum was collected after 1–17 weeks, depending on model, and analysed using morphometry and immunocytochemistry. For each group, intestinal mucosa and muscle layer thicknesses, neuronal numbers and relative proportions of neurons immunoreactive (IR) for nNOS or VIP were estimated. No alterations in mucosa or muscle layer thicknesses were noted in any of the groups. Loss of myenteric neurons and an increased number of VIP‐IR submucous neurons were found in mouse ileum 7 days after pMCAO. None of the global ischaemia models showed any alterations in neuronal survival or relative numbers of VIP‐ and nNOS‐IR neurons. We conclude that focal cerebral ischaemia and global cerebral ischaemia influence enteric neuronal survival differently. This is suggested to reflect differences in peripheral neuro‐immune responses.     

Modifications by stretches of the mechanical response of isolated cerebral and extracerebral arteries to vasoactive agents

Summary Length-tension relationship was compared in helically cut strips of canine cerebral, coronary, mesenteric, renal, and femoral arteries. Tension developed progressively by increasing the stretch; with the same strain, a greater passive tension developed in cerebral than in extracerebral arteries. The peak active tension developed by serotonin (cerebral, coronary), norepinephrine (mesenteric, renal and femoral) or K⁺ (coronary) was obtained at a resting tension of 1.5 g (other than coronary) or 2.0 g (coronary). Papaverine (10^–4 M) caused a relaxation in cerebral arterial strips contracted with serotonin to a level lower than that prior to the addition of serotonin, the relexation from the initial level of tension being related directly to the stretch applied. The relaxing effect of adenosine was related directly to stretches of cerebral arterial strips. It seems likely that a rise of intra-arterial pressure effects a greater increase in the wall stiffness in cerebral than in extracerebral arteries. The responsiveness to vasoconstricting and vasodilating agents of both cerebral and extracerebral arteries appears to increase when the arteries are distended.     

Effect of nitroglycerin on regulation of the cerebral circulation

Investigations by the use of radioisotopes and electromagnetic and resistographic methods showed that nitroglycerine increases the cerebral blood flow and lowers the tone of the intracranial vessels. It also has a marked depriming effect on the central regulation of the cerebral circulation, inhibits cerebrovascular reflexes, and has a protective effect in experimental disturbances of the cerebral circulation of adrenergic nature.Laboratory of Pharmacology of the Nervous System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 9, pp. 1081–1083, September, 1976.     

尼麦角林治疗慢性脑供血不足80例临床分析

目的观察尼麦角林对治疗慢性脑供血不足的临床疗效。方法 160例慢性脑供血不足患者随机分为治疗组和对照组。治疗组在基础治疗的同时,给予尼麦角林10 mg,口服,3次/日;对照组给予尼莫地平20 mg,口服,3次/日,疗程1个月。观察临床有效率及经颅彩色多谱勒超声(TCD)检查的结果在治疗前后2组之间的变化。结果治疗组临床有效率及TCD指标改善情况均优于对照组,2组间差异具有统计学意义。结论尼麦角林治疗慢性脑供血不足安全可靠。     

Effect of vasoactive intestinal polypeptide on cerebral blood flow in the goat

The effect of vasoactive intestinal polypeptide (VIP) on the cerebral blood flow was investigated in the goat. An electromagnetic flow probe was placed around the internal maxillary artery for continuous measurement of ipsilateral blood flow. Intraarterial injection of VIP resulted in a dose-dependent increase in the cerebral blood flow. The effect was not antagonized by any of the antagonists atropine, propranolol, phentolamine and naloxone administered intraarterially 1 min before VIP. It is discussed that VIP may play a physiological role in the local blood flow regulation in the CNS.     

Action of sympathomimetic drugs on the bronchial circulation of the horse

In the quietly standing horse I.V. administration of adrenaline decreased, and of dobutamine increased, bronchial artery flow. These changes paralleled changes in arterial pressure. With phenylephrine and noradrenaline bronchial artery flow decreased while arterial pressure increased, indicating active vasoconstriction in the bronchial circulation. With clenbuterol an increase in bronchial artery flow was accompanied by a decrease in systemic blood pressure, indicating bronchial arterial vasodilatation. We conclude that alpha-constrictor and beta 2-dilator receptors are present in the bronchial artery bed and that stimulation of these receptors could explain changes in flow seen in the horse during exercise and anaesthesia.     

Effect of adrenergic blockade on autoregulation of the cerebral blood flow during orthostatic tests

In experiments on rats under local anesthesia the action of phentolamine and propranolol on autoregulation of the cerebral blood flow (ACB) was studied during orthostatic tests (OT). The cerebral blood flow was measured in the carotid system, the venous pressure in the cerebral vessels, and the perfusion pressure in the carotid arteries; the resistance of the cerebral vessels was calculated. OT were simulated by tilting a special table with the animal (head upward or downward) through 40–80° from the horizontal plane. The results showed that adrenergic blockade in most cases of OT disturbed ACB: phentolamine led to a passive increase in the cerebral blood flow in response to an increase in perfusion pressure, whereas propranolol, on the other hand, caused a passive decrease in the cerebral blood flow in response to a fall of perfusion pressure.Department of Pharmacology, Pyatigorsk Pharmaceutical Institute. (Presented by Academicaian of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 9, pp. 309–311, September, 1978.     

Effect of methylapogalanthamine on tone of the cerebral,extracranial, and peripheral vessels

Acute resistographic experiments on anesthetized and unanesthetized cats showed that methylapogalanthamine lowers the general arterial pressure and the tone of the cerebral, extracranial, and femoral vessels. The effect on the femoral vessels is the strongest. A biphasic (dilator-constrictor) response was frequently observed. Methylapogalanthamine weakened the constrictor response of the intra- and extracranial vessels to stimulation of the cervical sympathetic nerve. Anesthesia potentiated, whereas rausedil weakened the vasodilator effect of methylapogalanthamine.Department of Pharmacology, Pyatigorsk Pharmaceutical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éxperimental'noi Biologii i Meditsiny, Vol. 86, No. 10, pp. 438–441, October, 1978.     

Sympathetic nervous control of the cerebral circulation in sleep

Cerebral vessels are extensively innervated by sympathetic nerves arising from superior cervical ganglia, and these nerves might play a protective role during the large arterial pressure surges of active sleep (AS). We studied lambs (n=10) undergoing spontaneous sleep-wake cycles before and after bilateral removal of the superior cervical ganglia (SCGx, n=5) or sham ganglionectomy (n=5). Lambs were instrumented to record cerebral blood flow (CBF, flow probe on the superior sagittal sinus), carotid arterial pressure (P(ca)), intra-cranial pressure (P(ic)), cerebral perfusion pressure (Pcp=Pca-Pic) and cerebral vascular resistance (CVR). Prior to SCGx, CBF (mL min-1) was significantly higher in AS than in Quiet Sleep (QS) and Quiet Wakefulness (QW) (17+/-2, 13+/-3, and 14+/-3 respectively, mean+/-SD, P<0.05). Following SCGx, baseline CBF increased by 34, 31, and 29% respectively (P<0.05). CVR also decreased in all states by approximately 25% (P<0.05). During phasic AS, surges of Pca were associated with transient increases in Pcp, Pic and CBF. Following SCGx, peak CBF and Pic during surges became higher and more prolonged (P<0.05). Our study is the first to reveal that tonic sympathetic nerve activity (SNA) constricts the cerebral circulation and restrains baseline CBF in sleep. SNA is further incremented during arterial pressure surges of AS, limiting rises in CBF and Pic, possibly by opposing vascular distension as well as by constricting resistance vessels. Thus, SNA may protect cerebral microvessels from excessive distension during AS, when large arterial blood pressure surges are common.