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Biomedical subjects

M Takayasu

Publications and source records attributed to M Takayasu.

At least 19 recordsLinked to original sources

Effects of adrenomedullin, calcitonin gene-related peptide, and amylin on cerebral circulation in dogs.

The effect of human adrenomedullin on cerebral circulation was investigated in dogs in vivo and in vitro. Bolus administration of adrenomedullin or its homologous peptides, calcitonin gene-related peptide (CGRP) and amylin, into the vertebral artery induced a dose-dependent increase in vertebral blood flow. The potencies of adrenomedullin and CGRP were similar and approximately 100 times more than that of amylin. The effects of adrenomedullin and CGRP were inhibited by CGRP8-37, an antagonist of CGRP. In contrast to substance P, adrenomedullin did not induce an increase in blood flow after prior administration of CGRP. Pretreatment with either NG-nitro-L-arginine methyl ester or indomethacin did not affect the adrenomedullin-induced increase in blood flow. Intracisternal administration of adrenomedullin induced dilation of the basilar and other major cerebral arteries in a dose-dependent manner, accompanied by an increase in the concentration of cyclic AMP in the cerebrospinal fluid. Adrenomedullin also induced relaxation of isolated basilar and middle cerebral arterial rings. These data suggest that adrenomedullin induces vasodilation of cerebral arteries and an increase in vertebral blood by acting at CGRP receptors positively coupled to adenylate cyclase, and that these effects are not dependent on nitric oxide or prostaglandin formation.

Adrenomedullin

Central cardiovascular effects induced by intracisternal PACAP in dogs.

The cardiovascular responses to intracisternally administered pituitary adenylate cyclase-activating polypeptide (PACAP) were investigated and compared with those of vasoactive intestinal peptide (VIP) in anesthetized dogs. Intracisternal administration of 10 nmol of PACAP-27 increased mean arterial blood pressure (MABP) significantly with a simultaneous increase of plasma arginine vasopressin and epinephrine concentrations. Intracisternal administration of VIP increased plasma arginine vasopressin concentration significantly but caused no appreciable change in MABP. Systemic infusion of the nonpeptide vasopressin V1 receptor antagonist OPC-21268 did not inhibit the PACAP-27-induced increase in MABP, whereas phentolamine, an alpha-adrenoceptor blocker, reversed the increase. Intracisternal pretreatment with the vasopressin V1 receptor antagonist [Pmp1, Tyr(Me)2]Arg8-vasopressin also inhibited the increase. These findings suggest that PACAP has a central pressor action by increasing sympathetic outflow, which is probably mediated by the vasopressinergic neural network. PACAP seems to play important roles in hormonal and neural control of systemic circulation.

Adrenergic alpha-Antagonists

Regional differences in the vasodilator response to vasopressin in canine cerebral arteries in vivo.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the regional differences in the in vivo vasodilator responses to vasopressin, which is thought to stimulate the release of nitric oxide from the endothelium, in canine cerebral arteries by angiography. METHODS: Angiograms were performed through a catheter inserted directly into the right vertebral artery and were taken periodically after the infusion of vasopressin. The diameters of various segments of the major arteries were measured using a computerized image analysis system. RESULTS: The bolus administration of vasopressin (10 pmol to 1 nmol) into the vertebral artery produced a long-lasting, dose-dependent vasodilation in the major cerebral arteries centering around the circle of Willis. One nanomole of vasopressin appeared to be the optimal dose for producing maximal vasodilation. The internal diameters of the basilar, posterior communicating, and internal carotid arteries experienced the most dilation (approximately 150% that of control) 2 minutes after the infusion of 1 nmol of vasopressin, followed by those of the middle cerebral, the intracranial portion of the vertebral, and the anterior spinal arteries (approximately 130% that of control). The extracranial portion of the vertebral artery (109.8 +/- 4.8% that of control, n = 4) was less sensitive to 1 nmol of vasopressin. Pretreatment with an intracisternal injection of 10 mumol of NG-monomethyl L-arginine suppressed the vasodilator effect of vasopressin and substance P, whereas it did not affect the response to vasoactive intestinal peptide. CONCLUSIONS: These results suggest that the arteries composing the circle of Willis at the base of the brain are more sensitive to nitric oxide release induced by vasopressin compared with other intracranial and extracranial arteries.

Angiography

Primary chronic intrasellar haematoma: a case report.

This report describes a rare case of primary intrasellar haematoma in a 66 year-old man with hypopituitarism. Computerized tomography (CT) and magnetic resonance imaging (MRI) showed an intrasellar cystic lesion with small suprasellar extension. Transsphenoidal surgery revealed that the lesion was a chronic haematoma, without evidence of a tumour or vascular anomaly. Pathological diagnosis confirmed this. This is the first report of a chronic intrasellar haematoma, which is probably primary.

Aged

Aneurysm in the skin: arterial fibromuscular dysplasia.

We describe a pulsatile aneurysm in the skin of 16-year-old boy that was found to be a sign of a systemic vascular disease, that is, arterial fibromuscular dysplasia. The patient had aneurysms in the renal, cerebral, coronary, and other arteries; he developed renovascular hypertension and had a cerebrovascular accident and acute myocardial infarction at 17 years of age. This disease has not been previously reported in the dermatologic literature.

Adolescent

Primary choroid plexus papilloma located in the suprasellar region: case report.

A 34-year-old woman with primary choroid plexus papilloma occurring in the suprasellar region is reported. No connection with the ventricular system was found during intraoperative observations. The findings of pathological examinations such as hematoxylin and eosin staining, transthyretin (prealbumin) immunoreactivity, and electron microscopy were consistent with choroid plexus papilloma. Radiologically, it was extremely difficult to differentiate from tuberculum sellae meningioma. To our knowledge, this is the first case of primary choroid plexus papilloma in this location reported in the literature.

Adult

An in vitro comparative study of conducting vessels and penetrating arterioles after experimental subarachnoid hemorrhage in the rabbit.

The reactivity of rabbit basilar artery and penetrating arteriolar microvessels was studied in vitro using an isometric-tension measurement technique and an isolated perfused arteriole preparation, respectively. Comparisons were made between reactivities of normal vessels and those obtained from animals subjected to experimental subarachnoid hemorrhage (SAH) 3 days prior to examination. Subarachnoid hemorrhage produced significant increases in basilar artery contraction in response to increasing concentrations of serotonin (5-hydroxytryptamine) (10(-9) to 10(-5) M) and prostaglandin F2 alpha (10(-9) to 10(-5) M) when compared to normal arteries. In addition, SAH attenuated the relaxing effect of acetylcholine following serotonin-induced contraction and of adenosine triphosphate after KCl-induced basilar artery contractions. In contrast to the changes observed in large arteries, cerebral microvessels did not demonstrate significant differences in spontaneous tone or in reactivity to a number of vasoactive stimuli including application of calcium, serotonin, and acetylcholine. On the other hand, small but significant changes in arteriolar responsiveness to changes in extraluminal pH and to application of KCl were noted. Findings from this study suggest that intracerebral resistance vessels of the cerebral microcirculation are not greatly affected by the presence of subarachnoid clot, in contrast to the large arteries in the basal subarachnoid space. The small changes that do occur are qualitatively different from those observed for large arteries. These findings are consistent with the observation of significant therapeutic benefit with the use of calcium channel blockers without changes in angiographically visible vasospasm in large vessels. It is likely, therefore, that calcium antagonists may act to decrease total cerebrovascular resistance at the level of the relatively unaffected microcirculation after SAH without changing large vessel diameter.

Acetylcholine

Differential effects of pentobarbital on intracerebral arterioles and venules of rats in vitro.

The vasoactive properties of pentobarbital (PB) were studied in intracerebral arterioles and venules (diameter, 30-90 microns). These vessels mediate changes in cerebrovascular resistance and capacitance, respectively. Mean control vessel diameters of arterioles and venules at pH 7.3 were 53.9 +/- 2.8 microns and 78.4 +/- 4.3 microns, respectively. Both arterioles and venules dilated when the pH of the extraluminal solution was lowered to 6.8 and constricted when the pH was raised to 7.6. PB, 10(-6) to 10(-2) mol/L, dilated intracerebral arterioles in a dose-dependent manner at pH 7.3, reaching a maximal dilation of 129.7 +/- 3.1% of control diameter at a dose of 10(-3) mol/L. In contrast, PB at 10(-6) to 10(-2) mol/L failed to produce significant changes in the diameter of intracerebral venules. In addition, PB at 10(-3) mol/L significantly inhibited arteriolar constriction induced by KCl (120 mmol/L), but not venular constriction. The present study suggests that intracerebral venules are relatively less responsive to PB than cerebral arterioles and peripheral veins. In addition to its effect on cerebral metabolism. PB may act to redistribute venous blood volume from cerebral veins to more responsive peripheral veins, thereby decreasing intracranial blood volume and intracranial pressure.

Animals

Differential effects of intra- and extraluminal endothelin on cerebral arterioles.

The differential effects of intraluminal and extraluminal application of endothelin, the endothelium-derived constricting factor, were studied in isolated intracerebral arterioles that were cannulated and perfused in vitro. Extraluminal and intraluminal application of 10(-8) M endothelin constricted the arterioles to 38.2 +/- 6.7 and 75.1 +/- 5.7% of the control diameter, respectively. Constrictions induced by either the intraluminal or the extraluminal application of endothelin were inhibited in a Ca(2+)-free solution. Nimodipine attenuated, but did not completely abolish, the constriction induced by the extraluminal application of endothelin, but it did abolish the constriction induced by the intraluminal application. The duration of vasoconstriction also differed between intra- and extraluminal application. Vessel diameter quickly returned to the control value as soon as intraluminal perfusion of endothelin was terminated. In contrast, the constriction induced by extraluminal application of endothelin lasted much longer and was difficult to reverse. The differential effect of intraluminal and extraluminal endothelin application appears to reflect the important barrier-function of the cerebrovascular endothelium of intracerebral arterioles.

Animals

Effects of hypothermia and hyperthermia on the reactivity of rat intracerebral arterioles in vitro.

The effects of hypothermia and hyperthermia on the cerebral microcirculation were studied using isolated perfused intracerebral (parenchymal) arterioles obtained from rats. In a temperature-dependent manner, hypothermia (20.0 degrees to 35.0 degrees C) dilated the spontaneous tone developed by the arterioles and also diminished their contractile response to potassium and prostaglandin F2 alpha. In contrast, hyperthermia (40.0 degrees to 45.0 degrees C) induced a biphasic response consisting of initial vasoconstriction and secondary vasodilation. Exposure of the vessels to 45.0 degrees C for 30 minutes irreversibly abolished the spontaneous tone and responsiveness of the arterioles when the temperature of the preparation was returned to 37.5 degrees C. In calcium-free solutions, however, the arteriolar diameter was not affected within a temperature range of 20.0 degrees to 45 degrees C. Furthermore, arterioles that had been in a calcium-free solution during exposure to 45 degrees C temperature recovered their viability at 37.5 degrees C. These results suggest that changes in ambient temperature alter calcium-induced contraction in arteriolar smooth muscle, and that the irreversible effects of hyperthermia on the arterioles are dependent upon extracellular calcium. These studies indicate that alterations in brain temperature may affect the pathogenesis of cerebral ischemia by mechanisms that are in part independent of parenchymal metabolism.

Analysis of Variance

Effects of HA1077, a novel calciumantagonistic spasmolytic agent on intracerebral arterioles of rats.

The effects of the new spasmolytic agent HA1077, which belongs to the calciumantagonists but acts by mechanisms different from those of conventional calcium channel blockers, on the cerebral microcirculation were studied in rats using isolated and cannulated intracerebral (parenchymal) arterioles of 50 microns average diameter. After the vessels had developed spontaneous tone, increasing concentrations of HA1077 were applied extraluminally. HA1077 induced vasodilation in a dose-dependent manner with a maximal increase of vessel diameter of 73.9 +/- 5.1% (mean +/- SEM, n = 5) at 10(-4) M and with half-maximal responses (ED50) of 1.00 x 10(-6) M. The extent of maximal vasodilation achieved by HA1077 was significantly greater than that induced by such conventional calcium channel blockers as diltiazem, verapamil, nifedipine and nimodipine (about 50% each in a previous report from our laboratory). Vasoconstriction induced by synthetic thromboxane A2 (10(-9) M to 10(-5) M) which is through to be highly dependent on intracellular calcium, was completely inhibited by 10(-4) M HA1077, whereas both verapamil and nimodipine at a concentration at maximal vasodilation effects (10(-5) M and 10(-7) M respectively) only partially inhibited such vasoconstriction. These results suggest that HA1077 may exert a more potent vasodilator effect on the cerebral microcirculation than do conventional calcium channel blockers.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Effects of STA-MCA anastomosis for ischaemic oculopathy due to occlusion of the internal carotid artery.

Effects of STA-MCA anastomosis on two patients with neovascular glaucoma due to occlusion of the internal carotid artery are presented. Both patients improved in visual acuity and central retinal artery pressure as well as in signs of transient ischaemic attack. Postoperative angiography showed a marked decrease in collateral flow through the ophthalmic artery, which is reversed from the normal direction, with the development of blood flow through the anastomosis. Discussion is offered indicating that the lack of collateral flow through both the anterior and posterior communicating arteries is important in addition to occlusion of the internal carotid artery in order to produce full-blown ischaemic oculopathy such as venous stasis retinopathy, neovascular glaucoma or rubeosis iridis. It is stressed that EC-IC bypass surgery should be performed soon after the appearance of ischaemia and before the development of neovascular glaucoma or rubeosis iridis in order to obtain normal vision. In ischaemic oculopathy the results of EC-IC bypass can be evaluated objectively and quantitatively by many noninvasive neuroophthalmological tests which are important in discussing the efficacy of the bypass surgery.

Arterial Occlusive Diseases

Endothelin-induced mobilization of Ca2+ and the possible involvement of platelet activating factor and thromboxane A2.

Endothelin (ET) caused transient and sustained elevations of cytosolic free Ca2+ concentrations ([Ca2+]i) in cultured rat and rabbit vascular smooth muscle cells (VSMC). Specific platelet activating factor (PAF) antagonists (CV-6209 and WEB-2086) and arachidonic acid (AA) cascade blockers (chlorpromazine, indomethacin, CV-4151 and AA-2414) potently inhibited the ET-induced increase in [Ca2+]i. Additionally, these compounds inhibited the PAF-induced increase in [Ca2+]i. These results suggest that PAF and thromboxane A2 (TXA2) may be involved in the mechanism of ET-induced mobilization of Ca2+ in cultured rat and rabbit VSMC.

Animals

Effects of inhibitory and excitatory amino acid neurotransmitters on isolated cerebral parenchymal arterioles.

The vasoactive properties of inhibitory (gamma-aminobutyric acid (GABA), glycine) and excitatory (glutamate, aspartate) amino acid neurotransmitters were studied in isolated rat cerebral parenchymal arterioles. None of these neurotransmitters had a significant effect on vessel diameter at concentrations between 10(-9) and 10(-3) M, except for 10(-3) M glycine. These amino acid neurotransmitters are unlikely to play a role in regulation or pathophysiology of the cerebral microcirculation by directly changing vascular diameter.

Amino Acids

Calcium dependence of intracerebral arteriolar vasomotor tone and constrictor responses in rats.

The purpose of our study was to determine in rats the dependence of constrictor responses of intracerebral (parenchymal) penetrating arterioles on extracellular calcium. Vessel diameter was monitored in vitro, after spontaneous tone had developed. When the organ bat solution was changed from a physiological solution to a Ca2+-free one containing 0.5 mM EGTA, these vessels showed rapid and marked vasodilation to a mean +/- SEM of 159.8 +/- 8.2% of control (p = 0.018). After 3 minutes of pretreatment with Ca2+-free solution, constrictor responses to solutions of 140 mM KCl, pH 8.0, or 10(-4) M prostaglandin F2 alpha, were completely abolished, except for small transient contractions with the latter (6.6 +/- 1.8%). When vasoconstrictors were applied simultaneously with the Ca2+-free solution, all vessels still dilated to 159.8 +/- 8.4% (KCl), 146.7 +/- 6.1% (pH 8.0), and 124.3 +/- 9.1% (prostaglandin 2 alpha) of control (p = 0.018). Our results suggest that both vasomotor tone and constrictor responses in intracerebral arterioles are highly dependent upon activation from an extracellular calcium source.

Animals

Spontaneous tone of cerebral parenchymal arterioles: a role in cerebral hyperemic phenomena.

An isolated cerebral arteriole preparation was used to test the hypothesis that a temporary reduction in transmural pressure causes a subsequent vasodilation mediated by mechanisms intrinsic to the vessel wall. Thirty-five cerebral vessels of 44.7 +/- 1.4 microns (+/- standard error of the mean) mean diameter were cannulated in vitro and pressurized at a transmural pressure of 60 mm Hg: after an equilibration period the vessels developed spontaneous tone. When transmural pressure was decreased to 0 mm Hg for a period of 4 minutes then returned to 60 mm Hg, vessels dilated to 155.1% +/- 6.8% of control diameter before gradually redeveloping spontaneous tone in 5.5 +/- 0.7 minutes. Varying the duration of the period during which transmural pressure was at 0 mm Hg had no significant effect on the degree of vasodilation. Conversely, varying the level of decreased transmural pressure between 0 and 20 mm Hg significantly affected both the magnitude of vasodilation and the time course of spontaneous tone recovery. These findings indicate that a temporary period of decreased transmural pressure may result in a loss of spontaneous tone in the resistance vessels of the cerebral microcirculation. Mechanisms intrinsic to the vessel wall may play a significant role in the early stage of post-reperfusion hyperemia. Such mechanisms could also be implicated in other hyperemic phenomena affecting the cerebral circulation, such as the rapid increase in intracranial pressure after subarachnoid hemorrhage, the development of the normal perfusion pressure breakthrough phenomenon, and the initiation of intracranial pressure plateau waves.

Animals

Effects of neuropeptide Y on canine cerebral circulation.

The effects of neuropeptide Y (NPY) on the vascular tone of isolated cerebral arteries and vertebral blood flow (VBF) were studied in dogs. NPY elicited a dose-dependent contraction of arteries derived from the brain with ED50 values of 2 nM for the middle cerebral and basilar arteries. Arteries from the neck did not respond to NPY. Intra-arterial administration of NPY as a bolus reduced the VBF dose dependently, with no significant alteration of mean arterial blood pressure and heart rate. The decrease in VBF developed slowly and had a long duration, which was consistent with the observations made in vitro. NPY suppressed the contractile effect of noradrenaline (NA) on isolated cerebral arteries and pretreatment with NPY suppressed the effect of NA on VBF, indicating that NPY contributes to the inhibitory modulation of postsynaptic adrenergic mechanisms. These findings suggest that NPY could have a role in the regulation of cerebral circulation.

Animals

The effects of an intracellular calcium antagonist HA 1077 on delayed cerebral vasospasm in dogs.

The effectiveness of calcium antagonists on a chronic cerebral vasospasm after an SAH is still under debate. Calcium channel blockers such as nimodipine, nifedipine etc. can dilate spastic arteries by intrathecal administration, but not by systemic (iv or po) use. HA 1077 is a novel and potent calcium antagonist vasodilator which is considered to act by employing different mechanisms from the usual calcium channel blockers since it inhibits 1. calcium ionophore A 23187 induced contraction in arterial strips and 2. phenylephrine induced contraction in calcium free media, suggesting that its site of action is in the intracellular space. HA 1077 is water soluble and relatively stable in light. In the present study, the efficacy of HA 1077 was evaluated on dogs by using the spiral arterial strips in vitro and by angiography in vivo. In the arterial strips from the control dogs, a 50% relaxation of KCl (15 mM) induced contraction was obtained by a 10(-6) M HA 1077 for the "intracranial" basilar and middle cerebral arteries, while a 10(-5) M was needed to obtain the same effect for the "extracranial" common carotid and vertebral arteries, indicating that HA 1077 is more effective for the intracranial arteries. A vasospasm was produced by the "two haemorrhage" model of Varsos et al. The average angiographic diameter of the basilar artery was reduced to 60% of the control on SAH day 7. Intravenous infusion of HA 1077 (0.5-3 mg/kg/30 min) significantly dilated the spastic basilar artery (up to 20-30%), for over 2 hours. A fall in the systemic BP remained less than 20% during this time.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine