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)

Administration of 10 micrograms of substance P intrathecally to the spinal T9 level of the adult rat, anaesthetized with urethane, provoked an increase in free catecholamines in plasma taken from the inferior vena cava. Adrenaline levels at 1 min after administration were 154.8 +/- 10.8% (mean +/- SE; n = 11) of preadministration levels and noradrenaline levels were 153.5 +/- 11.8% of preadministration levels. Differences between the values of free catecholamines in animals given substance P vs those given vehicle only were statistically significant at 1 and 10 min postinjection, but not at 30 min. Administration of a substance P analogue with central antagonistic properties 15 min before substance P was given prevented expression of the effects of substance P. These results suggest that substance P may be an excitatory chemical mediator of synaptic transmission in spinal pathways controlling adrenal medullary output. Thus dysfunction of substance P mechanisms may underlie some animal models of hypertension and may be involved in some cases of essential hypertension in man as well as in autonomic dysfunction associated with some neurological entities.
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PMID:Substance P given intrathecally at the spinal T9 level increases adrenal output of adrenaline and noradrenaline in the rat. 241 Aug 14

The most important central autonomic pathways in the control of arterial blood pressure are the baroreceptor reflex pathway and descending pathways from the hypothalamus. Central neurotransmitters in these pathways are L-glutamate, substance P, norepinephrine (NE), gamma-aminobutyric acid, epinephrine, neuropeptide Y, and acetylcholine. At peripheral autonomic neurovascular junctions, there are prejunctional alpha 2- and dopamine-2 receptors, which inhibit NE release, and beta- and serotonin receptors, which stimulate NE release. Postjunctional alpha 1-receptors open sodium channels, open calcium channels via phosphoinositol release, and release intracytoplasmic calcium. Postjunctional alpha 2-receptors, which are extrasynaptic, inhibit adenylate cyclase and also open calcium channels. In animal models of hypertension, changes in alpha-receptor density have been reported. In spontaneously hypertensive rats, increased renal beta- and alpha 2-receptors, respectively, may enhance renin release and cause sodium and water retention. In experimental (renovascular) hypertension, vascular postsynaptic (vasoconstrictor) alpha 1- and alpha 2-receptors are increased. In both models of hypertension, beta-receptors are down-regulated. Selective alpha 1-antagonists, such as indoramin and prazosin, decrease arterial blood pressure by postsynaptic alpha 1-blockade; alpha 2-receptor inhibition of NE release is unaffected so that there is no beta-receptor-mediated tachycardia.
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PMID:Alpha-adrenoreceptors in hypertension. 242 93

Substance P and the N-terminal sequences SP1-9, SP1-7, SP1-4 and SP1-2 were investigated in their action on stress related alterations in blood pressure behaviour, stress related disturbances in conditioned reflex learning behaviour, alterations in the endogenous opioid system and on the blood pressure behaviour of spontaneously hypertensive rats. In addition the occurrence of vegetative effects such as acute hypertension and histamine release from mast cells were investigated. The results of this work show that N- and C-terminal sequences of the Substance P molecule differ in their actions. Whereas the vegetative effects decrease if the SP molecule is shortened from the C to the N-terminus the "antistress effect" of the Substance P molecule remains unchanged. Whereas the N-terminal tetrapeptide SP1-4 can be considered "essential" for the "antistress effect", the C-terminal pentapeptide of SP is considered to be the "essential sequence" for the vegetative effects. These results will open new possibilities for the synthesis of selectively acting SP-agonists.
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PMID:[The role of the N-terminal of the substance P molecule in its action in stress-related behavioral and blood pressure disorders]. 243 39

Administration of 10 micrograms of substance P intrathecally at the spinal T9 level of the unanaesthetized and the anaesthetized rat provoked an increase in arterial pressure and an increase in heart rate. Both cardiovascular responses began within 1-2 min of administration, and the peak of each occurred at 4-10 min. In the anaesthetized rat, which gave rise to the bulk of the responses reported, peak arterial pressure was ca 20 mm Hg greater than pre-administration levels, and peak heart rate was greater by ca 50 beats per min. Similar administration of vehicle failed to alter either parameter. Arterial pressure and heart rate in substance P-treated rats were significantly different from those in vehicle-treated rats up to 15-20 min after administration. Pretreatment with the sympathetic ganglion blocker, hexamethonium (10 mg/kg, i.v.), prevented the responses to intrathecal administration of substance P. Pretreatment with [D-Pro2, D-Phe7, D-Trp9]-substance P, an analogue with antagonist properties in the central nervous system, blocked both responses to substance P but failed to alter similar responses provoked by intrathecal administration of angiotensin II. Pretreatment with vehicle had no effect on responses to substance P or to angiotensin II. The antagonist also had partial agonistic effects. Both arterial pressure and heart rate were transiently increased, but this effect was reversed within 6 min; in the case of heart rate, values returned to the pre-application level but arterial pressure fell to a ca 15 mm Hg below this level. These results demonstrate a pharmacologically specific excitatory effect of substance P on spinal mechanisms controlling sympathetic output to the vessels and the heart; this output can be either via the adrenal medullae or via nerve pathways to the vessels and the heart. Our results also support the possibility that dysfunction of substance P systems at the spinal level may underly some models of hypertension and may be involved in some cases of essential hypertension in man, as well as in autonomic dysfunction associated with some neurological disorders.
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PMID:Substance P given intrathecally at the spinal T9 level increases arterial pressure and heart rate in the rat. 243 74

Substance P (SP) applied to the cerebral ventricles elevates arterial blood pressure (BP). This elevation is mediated by an increased sympathetic tone and, moreover, could be attenuated by intravenous (i.v.) SP. To check the assumption that a change of adrenoceptor efficiency might contribute to the attenuation, SP (5 ng/kg per min) was continuously given i.v. and 20 micrograms SP injected intracerebroventricularly (i.c.v.) in anaesthetized normotensive as well as hypertensive rabbits. The BP response to 5 micrograms noradrenaline (NA) was checked within a control period before SP was given and rechecked 30 min after i.c.v. SP with continued i.v. infusion. Under these circumstances SP altered the BP response to NA qualitatively and quantitatively. An initial BP drop was followed by a rise which was remarkably smaller in magnitude than that obtained within the control period. The BP response to phenylephrine (PHE), however, was not altered by the identical SP protocol. Substance P application only i.v. or only i.c.v. was ineffective. Moreover, no differences could be revealed between normotensive and hypertensive animals in the BP response to NA. It is concluded that the beta-adrenoceptor efficiency changed similarly in the normotensive and hypertensive rabbits with i.v. SP, provided sympathetic tone had previously increased. In this manner i.v. SP might modify an exaggerated sympathetic tone which might be implicated in the pathogenesis of arterial hypertension.
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PMID:Blood pressure response to intravenous noradrenaline is influenced by substance P in normotensive and hypertensive rabbits. 244 Oct 14

The localization and distribution of catecholamines, selected neuropeptides, and the cyclic nucleotide second messengers has been determined in the superior cervical ganglion of the stroke-prone variant of the spontaneously hypertensive rat (SHR) and its normotensive Wistar-kyoto (WKY) control. Significant alteration in the frequency of occurrence of dopaminergic small intensely fluorescent cell clusters was seen in the stroke-prone variant of the SHR. The immunofluorescent localization of cyclic AMP (cAMP) and cyclic GMP (cGMP) were also changed in the stroke-prone variant, as was the immunofluorescent staining quantity of the neuropeptides somatostatin and substance P. The morphological pattern of staining for the various compounds in the normotensive control (WKY) was equivalent to the Sprague-Dawley rat strain. The implications of the altered neurochemistry in the superior cervical ganglion on the high blood pressure, and the predisposition for stroke in this strain are discussed.
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PMID:Neurochemical differences in the superior cervical ganglion of the spontaneously hypertensive rat stroke-prone variant. 244 7

The distribution and density of nerves containing vasoactive intestinal polypeptide, substance P, and neuropeptide Y around the cerebral and peripheral blood vessels of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) were studied using an indirect immunofluorescence technique. Neonatal sympathectomy of SHRSP with anti-nerve growth factor and guanethidine was also carried out to study the effect of sympathectomy on the distribution of these nerves. Vasoactive intestinal polypeptide nerve density was higher in the veins and superior mesenteric artery of SHRSP than of WKY and lower in the cerebral arteries of SHRSP than of WKY, but no difference was found in the muscular mesenteric arteries. Sympathectomy reduced the density of these nerves in all the peripheral vessels but had little effect on the cerebral arteries. Density of substance P nerves was similar between SHRSP and WKY in the peripheral vessels but higher in the cerebral arteries of WKY than of SHRSP. Sympathectomy reduced the density of these nerves in the peripheral vessels but increased the density in some cerebral arteries of SHRSP. Neuropeptide Y nerve density was higher in the peripheral blood vessels of SHRSP than of WKY, and no difference was found in the cerebral arteries. Sympathectomy almost completely removed these nerves in the peripheral vessels but had no effect on the cerebral arteries. We suggest that some of the differences in nerve density between SHRSP and WKY, especially those in the peripheral blood vessels, may be related to the development of hypertension in the SHRSP.
Hypertension 1988 Feb
PMID:Peptide-containing nerves around blood vessels of stroke-prone spontaneously hypertensive rats. 245 64

This paper presents results on the function of the adrenal medulla, especially the influence of substance P (SP) on the cholinergic-adrenergic interaction. Interconnections between the function of SP and its role in the development and maintenance of hypertension as well as its role in stress and adaptation are investigated. Substance P acts only in situations with an increased nervous activity, for example, after stress-induced activation of the pituitary-adrenal and sympathetic-adrenal axis. Substance P normalizes stress-induced disorders by maintaining homeostasis in the catecholamine system. The basis of the antistress effect is the modulation of both biosynthesis and release of catecholamines in the adrenals. The homeostasis effect of SP, as well as the antistress effect do not require the complete sequence of the molecule. The N-terminal SP fragment is fully active and has no side effects.
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PMID:Relationship of substance P to catecholamines, stress, and hypertension. 245 60

Substance P (SP) plays an important role in central nervous and peripheral blood pressure regulation. Its effects include modulating influence on the adrenergic system and inhibition of stress-induced plasma noradrenaline increase in animal studies. In patients with essential hypertension (n = 45, WHO stages 1 and 2) the SP-like immunoreactivity (SPLIR) was found significantly (p less than 0.01) lower (1.36 +/- 0.23 pg/100 microliters) than in 24 normotensive subjects (4.54 +/- 0.72 pg/100 microliters). Furthermore, the influence of a mental stress test on SPLIR was investigated in patients with essential hypertension (n = 11, WHO stage 1) and compared with nine normotensive subjects. Whereas in normotensive subjects plasma SP increased under a standardized mental arithmetic test (4.03 +/- 0.48 to 4.74 +/- 0.56 pg/100 microliters), in hypertensive patients a decrease of SP from lower baseline levels (2.85 +/- 0.54 to 2.57 +/- 0.54 pg/100 microliters) was demonstrated. The significantly different changes of plasma SP in normotensive and hypertensive subjects under mental stress conditions had the opposite direction in comparison with the adrenergic reaction [higher and prolonged increase of plasma noradrenaline (NA) in the hypertensive group]. Under antihypertensive drug treatment with prazosin (4.5 mg/day, n = 10) or with captopril (450 mg/day, n = 10) an increase of plasma SP was registered. The results support the participation of SP in the pathogenesis of human hypertension and in therapeutic mechanisms. Lower plasma levels and decreased responsiveness of SP possibly represent the enhanced stress sensitivity in primary hypertension.
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PMID:Substance P in human essential hypertension. 245 74

The Substance P (SP) level in blood is lower in hypertensive individuals than in normotensive ones. Intravenous application of SP leaves the normotensive blood pressure largely unaffected, but decreases the enhanced blood pressure. Further studies on the effect of SP (i.v. application of 2.5 micrograms/kg b.w.) were performed on 26 primates; the results were as follows: With normotensive primates SP no effect on blood pressure. Upon repeated chasing and subsequent immobilization (load) the animals developed an arterial hypertension. Under the same load, the animals failed to develop hypertension if they were treated with SP 1 h before. A load-induced hypertension could be interrupted by injection of SP even after 3 weeks following initial load; the after-controls one year later revealed normotensive blood pressure values. Application of SP with two other animal groups with a manifest hypertonus lowered the blood pressure only transitorily. It is concluded that i.v. application of SP can prevent the development of stress-induced hypertension and, with existing manifest hypertension, leads to reduced blood pressure only transitorily. An indirect action with peripheral site of attack is assumed.
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PMID:[Long-term hypotensive effects of substance P on the stress induced hypertension of primates]. 246 94


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