Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The responses to intraluminally applied substance P (SP) were examined in isolated and perfused canine basilar arteries using the stainless-steel cannula inserting method. In control vessels with intact endothelium, this peptide induced a monophasic dilation at lower doses, and a biphasic response, i.e., an initial dilation followed by a secondary constriction at higher doses. After extraluminal treatment with oxyhemoglobin, the dilation was attenuated and the constriction was augmented. After endothelial removal with intraluminal saponin, the dilation was reduced and the constriction was enhanced significantly. This potentiated constriction was significantly depressed by indomethacin (a cyclooxygenase inhibitor), OKY-046 (a thromboxane synthetase inhibitor), and nimodipine (a calcium antagonist), but not by AA-861 (a lipoxygenase inhibitor). These results suggest that SP has two distinct effects (an endothelium-dependent dilation and a direct constriction) and that the potentiated constriction in the absence of endothelium may be related to the action of thromboxane A2, linked with calcium influx into the smooth muscle cells of cerebral arteries. This mechanism may be implicated in cerebral vasospasm after subarachnoid hemorrhage.
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PMID:Biphasic response to substance P in canine basilar arteries. 128 41

Oxyhemoglobin (Oxy-Hb) produced a concentration-dependent contraction of monkey, dog, and bovine cerebral artery strips. Treatment of Oxy-Hb with ascorbic acid suppressed the ability of Oxy-Hb to contract the arteries, especially in the monkey arteries. The ability of intracisternally applied Oxy-Hb to constrict the basilar artery in anesthetized dogs was diminished when Oxy-Hb was treated previously with ascorbic acid (AsA-Hb). The contraction caused by Oxy-Hb was suppressed by treatment with indomethacin and aspirin in isolated bovine cerebral arteries. Endothelium-dependent relaxations elicited by substance P and relaxations induced by stimulation of the vasodilator nerves with nicotine were suppressed by treatment with Oxy-Hb and AsA-Hb; however, the inhibitory effect of AsA-Hb was markedly less. Oxy-Hb attenuated nitroglycerin-induced relaxations in a dose-dependent fashion, whereas AsA-Hb in concentrations up to 1.6 x 10(-5) M did not significantly influence the relaxations. It is concluded that incubation of Oxy-Hb with ascorbic acid alters markedly the biological activity of Oxy-Hb; the vasoconstrictor activity is suppressed, and the ability to diminish vasodilator actions is minimized. These findings provide a rationale for the use of ascorbic acid in cisternal irrigation to prevent the development of cerebral vasospasm after a subarachnoid hemorrhage.
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PMID:Suppression of the cerebral vasospastic actions of oxyhemoglobin by ascorbic acid. 170 91

We compared responses to calcium ionophore A23187, vasopressin, and substance P in helical strips of dog middle cerebral, basilar, and posterior communicating arteries to obtain a better understanding of humoral control of cerebrovascular tone in different brain regions and its potential impact on mechanisms of cerebral vasospasm. A23187 relaxed these different arterial strips partially precontracted with prostaglandin F2 alpha to a similar extent. Vasopressin produced concentration-dependent relaxation in basilar and posterior communicating arterial strips, whereas middle cerebral arterial strips either contracted or relaxed slightly. Relaxations induced by A23187 and vasopressin were either abolished or converted to contractions by removal of the endothelium. In contrast, the relaxation of cerebral arterial strips to substance P was markedly attenuated but not abolished by endothelium denudation; the remaining relaxation was suppressed by indomethacin. In some cerebral arterial strips with intact endothelium, substance P caused a transient contraction that was reversed to a relaxation by indomethacin or ONO-3708, a prostaglandin antagonist. In arterial strips denuded of endothelium from the same dogs, substance P always produced relaxations. Relaxations of cerebral arterial strips to A23187 and vasopressin appear to be mediated by endothelium-derived relaxing factor. The function of vasopressin receptors in endothelial cells differs markedly in basilar and posterior communicating arteries versus middle cerebral arteries. Substance P-induced relaxations appear to be primarily associated with endothelium-derived relaxing factor and with prostaglandin I2, whereas contractions appear to be mediated by endothelium-derived prostaglandins.
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PMID:Endothelium-dependent and -independent responses to vasodilators of isolated dog cerebral arteries. 246 Sep 77

We exposed helical strips of dog middle cerebral arteries to oxyhemoglobin for 5 hours, rinsed them with bathing medium, and stored them overnight; we compared the responses of strips thus treated with the responses of strips without oxyhemoglobin treatment. Relaxation induced by nicotine was abolished by hexamethonium and was markedly inhibited after exposure to oxyhemoglobin. A low concentration of KCl (5 mM) elicited relaxation that was abolished by ouabain and significantly reduced by oxyhemoglobin. Endothelium-dependent relaxation caused by calcium ionophore A23187 was attenuated, and that caused by substance P was reversed to contraction after exposure to oxyhemoglobin. Contraction elicited by substance P also depended on endothelium and was abolished by indomethacin. Relaxation induced by TRK-100, a stable analogue of prostaglandin I2, was moderately attenuated by oxyhemoglobin. On the other hand, concentration-dependent relaxation induced by papaverine and contractile responses to KCl, serotonin, and prostaglandin F2 alpha were not affected by oxyhemoglobin. Our results indicate that vasodilations mediated by vasodilator nerves, the electrogenic sodium pump, endothelium-derived relaxing factor, and prostaglandin I2 were impaired in dog cerebral arteries exposed to oxyhemoglobin. After exposure to oxyhemoglobin, vascular endothelium appears to participate in cerebroarterial contraction via a release of vasoconstrictor prostaglandins. These actions of oxyhemoglobin may be involved in the genesis of cerebral vasospasm after subarachnoid hemorrhage.
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PMID:Prolonged exposure to oxyhemoglobin modifies the response of isolated dog middle cerebral arteries to vasoactive substances. 247 Jan 67

Experiments were performed on isolated human cerebral arteries to evaluate the role desensitization and tachyphylaxis might play in preventing certain agonists from producing prolonged vasoconstriction after subarachnoid hemorrhage. In addition, the antiproteases leupeptin and pepstatin were studied to ascertain whether these peptides might inhibit contraction as does antithrombin III. The maximal contraction to KCl was used as a standard for comparing the responses elicited by the agonists, the decay of the responses to the agonists over 15 minutes was used as an index of desensitization, and the percentage of decrease in response to a second application of the agonist over the first was a measure of tachyphylaxis. The results showed that desensitization and tachyphylaxis greatly reduced or abolished the contractile responses to norepinephrine, serotonin, angiotensin II, arginine vasopressin, substance P, neuropeptide Y, neurotensin, thrombin, uridine triphosphate, linoleic acid, melittin, and cathepsin D. Moreover, some arteries failed to respond to some of these agonists, and no contractile response was elicited by acetylcholine or bradykinin. In contrast, prostaglandins E2, D2, and F2 alpha, as well as plasmin, produced sustained contractions, without tachyphylaxis, but only prostaglandin E2 and plasmin produced contractions at concentrations of 10(-7) M or less that were comparable to those of KCl. None of the antiprotease peptides inhibited the responses to KCl whereas small concentrations (6 X 10(-8) M) of antithrombin III did. The results support the hypotheses that the phenomenon of desensitization and tachyphylaxis would prevent many diverse agents from acting as spasmogens and that substances like antithrombin III present in the cerebrospinal fluid after hemorrhage could immediately protect patients from cerebral vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacodynamic evaluation of human cerebral arteries in the genesis of vasospasm. 368 86

Cerebral vasospasm following subarachnoid hemorrhage was induced in the squirrel monkey in order to evaluate the involvement of cerebrovascular sensory nerves in the development of the vasospasm. A unilateral surgical section of the trigeminal nerve at post- but not at pre-Gasserian level caused constriction of the major ipsilateral cerebral arteries. A pre- or postganglionic trigeminal lesion induced an increased glucose uptake globally without influencing the cerebral blood flow. Following a subarachnoid hemorrhage, the decrease in cerebral blood flow was similar of that seen in control animals, while post-ganglionically lesioned animals had an additional increase in glucose uptake. Intrathecal injection of gamma-globulin against substance P prevented the occurrence of vasospasm and the decrease in cerebral blood flow, while calcitonin gene-related peptide (CGRP) anti-gamma-globulin injection significantly reduced the resting vessel diameter and did not influence spasm development. It is concluded that a nervous reflex mechanism could underlie cerebral vasospasm. The cerebrovascular sensory nerves have both a peripheral and a central function. A peripheral or axon reflex mechanism exerts a tonic effect on the cerebral arteries. Central neurotransmission seems to be involved in the regulation of cerebral metabolism and possibly in the coordination of cerebral blood flow and glucose metabolism. CGRP could be the transmitter involved in a peripheral axon reflex and substance P might be the neurotransmitter conveying information to the brainstem vascular centers.
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PMID:Cerebrovascular sensory innervation involved in the development of cerebral vasospasm following a subarachnoid hemorrhage. 753 Jul 34

Bradykinin, substance P and vasopressin induced a vasodilatation followed by a vasoconstriction in control perfused canine basilar arteries with endothelium. The dilatation was significantly reduced and the constriction was significantly enhanced by endothelial removal with saponin. The potentiated constriction was significantly blocked by sodium ozagrel, a thromboxane synthetase inhibitor. These results suggest that the dilatation due to these neuropeptides may depend on endothelium-derived relaxing factor, and that the augmented constriction after endothelial removal may be related to the thromboxane A2 production in cerebral arterial smooth muscles. This mechanism following the damage of endothelium might be implicated in cerebral vasospasm after subarachnoid haemorrhage.
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PMID:Origin of thromboxane-mediated constriction due to neuropeptides in canine basilar artery. 782 46

The stainless steel cannula method was applied to isolated and perfused canine basilar arteries to examine the role of endothelium in the responses to intraluminal vasoactive substances. After intraluminal treatment with saponin to remove the endothelium, the monophasic constrictions to potassium chloride and prostaglandin F2 alpha were potentiated, while those to phenylephrine (alpha 1-adrenoceptor agonist) and 5-hydroxytryptamine were not changed. Xylazine (alpha 2-adrenoceptor agonist) and acetylcholine induced a constriction preceded by a small dilation in controls. The response to xylazine was not modified, while the constriction to acetylcholine was augmented after endothelium removal. Bradykinin, substance P and vasopressin caused a dilation in lower doses, and a dilation followed by a secondary constriction in higher doses in controls. The dilations to these peptides were reduced and the constrictions were enhanced after endothelial removal. Adenosine triphosphate produced a biphasic response, i.e., a dilation followed by a constriction, which was occasionally preceded by a small constriction in higher doses, and only the dilation in lower doses was attenuated. The monophasic dilation to adenosine was potentiated, while the papaverine-induced dilation was not influenced by endothelial removal. After extraluminal treatment with oxyhemoglobin, the dilations to calcium ionophore A23187 and thimerosal were attenuated, while the constriction to acetylcholine was enhanced. The dilations to substance P and vasopressin were depressed, and the constrictions were potentiated. The monophasic dilation to sodium nitroprusside was augmented, while that to papaverine was not changed. These results suggest that the endothelium may play important roles not only in producing endothelium-derived relaxing factors but also in modulating the calcium influx into the smooth muscle cells. The mechanisms of altered responsiveness might be implicated in cerebral vasospasm following subarachnoid hemorrhage.
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PMID:Effects of endothelium removal by saponin and of oxyhemoglobin on canine cerebrovascular responses. 783 71

We investigated the effect of endothelin-1 on relaxation responses induced by vasodilator substances in canine middle cerebral arteries to better understand regulation of cerebrovascular tone and its potential impact on mechanism of cerebral vasospasm. Endothelin-1 elicited concentration-dependent contractions in helical strips of canine cerebral arteries (EC50; 4.62 x 10(-9) M). Pretreatment with 10(-9) M endothelin-1 significantly reduced endothelium-dependent relaxation elicited by substance P and endothelium-independent relaxations by nitroglycerin, prostaglandin I2, and KCl. Although endothelin-1 in a lower concentration (10(-10) M) did not affect these endothelium-independent relaxations, it did inhibit endothelium-dependent relaxation caused by substance P. A low concentration (10(-10) M) of endothelin-1 also significantly reduced endothelium-dependent relaxation of canine mesenteric arteries induced by acetylcholine. Other vasoconstrictor peptides such as angiotensin-II and vasopressin did not inhibit endothelium-dependent and -independent relaxations. These results indicate that endothelin-1 not only produces cerebral vasoconstriction but also interferes with vasodilator mechanisms and that endothelium-dependent vasodilation is more sensitive to the inhibitory effect of endothelin-1 than endothelium-independent vasodiltion.
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PMID:Suppression of cerebral vasodilation with endothelin-1. 853 97

Cisternal blood injection in the rat and squirrel monkey produces a biphasic cerebral vasospasm, a decrease in cerebral blood flow (CBF) and an increase in glucose uptake (CMRglu) due to an anaerobic glucolysis actually representing a decrease in metabolism. Lesioning of the A2-nucleus, its ascending cathecolamine pathways or their projection site, the median eminence in the hypothalamus, prevents the occurrence of spasm. A unilateral postganglionic trigeminal lesion causes an ipsilateral constriction of the cerebral arteries while a preganglionic lesion does not affect the baseline arterial diameter. Both kinds of trigeminal lesions induce a global increase in glucose uptake of about 50% without influencing CBF. Following subarachnoid hemorrhage (SAH) the decrease in CBF in both groups of lesioned animals is similar to that seen in controls. After SAH there is no further change in CMRglu in the animals with a preganglionic lesion, while in the postganglionically lesioned animals there is an additional increase in CMRglu of about 50% as compared to controls or animals with a preganglionic lesion. Treatment with the peptidergic substance P (SP) antagonist, spantide, or gammaglobulin against SP prevents or significantly reduces the degree of spasm and the changes in flow and metabolism normally seen post-SAH. The non-peptidergic neurokinins NK1 and NK3 antagonists do not influence flow and metabolism in SAH animals. The NK2 seems to change both flow and metabolism post-SAH in rats.
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PMID:Trigeminal nerve and brainstem catecholamine systems in cerebral vasospasm. 1023 97


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