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)

Hemodynamic stability is better preserved during bicarbonate hemodialysis compared to acetate. We have studied the effects of bicarbonate (HDB) and acetate hemodialysis (HDA) on plasma levels of vasoactive substances. The treatments were performed for 270 min. A cuprophan plate dialyzer was used. The ultrafiltration volume and the ultrafiltration rate were identical in the individual patients during the two treatments. In the case of vasoconstrictors there was an increase in neuropeptide Y (NPY) (20%, p < 0.01) during HDB and arginine vasopressin (AVP) was unchanged. Unlike this was the response during HDA when there was no change in NPY and a decrease in AVP (38%, p < 0.01). An increase in noradrenaline (NA) (41%, p < 0.05) occurred during HDA different from what was the case during HDB. There was a gradual increase in renin (PRA) during both HDB (141%, p < 0.05) and HDA (148%, p < 0.01). With respect to vasodilators there were no differences between the two regimes regarding calcitonin gene-related peptide (CGRP) and motilin (MOT). The change in substance P (SP) during the treatments was also similar but somewhat more pronounced during HDB. Thus, an initial rise occurred (HDB, 81%, p < 0.01; HDA, 36%, p < 0.05) followed by a decrease (HDB, 26%, p < 0.05) or a tendency to decrease (HDA, 12%, p = 0.058) during the remaining part of the treatment. A rise in beta-endorphin (beta-END) occurred during HDB (10%, p < 0.05) but not during HDA. An increase in vasoactive intestinal peptide (VIP) occurred during HDB (27%, p < 0.05) different from the decrease during HDA (11%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in plasma levels of vasoactive substances during routine acetate and bicarbonate hemodialysis. 800 26

During bicarbonate hemodialysis, there is an increase in peripheral vascular resistance of nonadrenergic origin, counteracting the hypotensive effect of fluid removal during the course of the dialysis. In this study, the plasma levels of vasoactive regulatory peptides, noradrenaline and renin, were investigated in 11 patients with chronic renal failure during standard bicarbonate hemodialysis (STHD) for 270 min. As regards vasoconstrictors, an increase in gamma 2-melanocyte-stimulating hormone (gamma 2-MSH), neuropeptide Y (NPY) and plasma renin activity (PRA) occurred. However, arginine vasopressin and noradrenaline were unchanged. With respect to vasodilators, calcitonin gene-related peptide was not changed. An initial increase in beta-endorphin (beta-END) occurred, followed by a decrease during the remaining part of the treatment. Motilin decreased during the first part of the treatment but increased to the baseline level during the latter part. An increase in substance P was observed while vasoactive intestinal peptide decreased. We conclude that an increase in vasoconstricting substances (gamma 2-MSH, NPY, PRA) occurs during STHD, probably owing to the decrease in plasma volume. With the exception of beta-END, the changes in vasodilators were fairly small. The data suggest that vasoactive substances might participate in the hemodynamic response to hemodialysis.
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PMID:Changes in plasma levels of vasoactive peptides during standard bicarbonate hemodialysis. 844 68

The hemodynamic response to isolated ultrafiltration (IUF) is characterized by a vasoconstriction, while there is no significant change in peripheral vascular resistance during isovolemic bicarbonate hemodialysis (IVHD). The present investigation was designed to study the plasma levels of vasoactive regulatory peptides together with noradrenaline (NA) and plasma renin activity (PRA) in 11 patients during sequential hemodialysis (SQHD) - IUF for 60 min, followed by IVHD for 210 min. During IUF, the vasoconstrictors arginine vasopressin (AVP), gamma 2-melanocyte-stimulating hormone (gamma 2-MSH), neuropeptide Y (NPY), NA and PRA increased. During IVHD, NPY and PRA remained unchanged on a higher level. A decrease in AVP below the baseline and in gamma 2-MSH and NA to the baseline levels occurred during IVHD. In the case of vasodilators, there were no changes in calcitonin gene-related peptide or motilin during SQHD. An increase in beta-endorphin (beta-END) occurred during IUF, followed by a decrease during IVHD. Substance P and vasoactive intestinal peptide were unchanged during IUF but decreased during IVHD. We conclude that SQHD is characterized by an increase in all the measured vasoconstrictors during IUF in response to loss of fluid, and by a decrease in some vasoconstrictors (AVP, gamma 2-MSH, NA) during IVHD. With the exception of beta-END, there were no changes or only minor ones in vasodilators during SQHD. There are changes in plasma levels of vasoactive substances during SQHD but the importance of these changes for the hemodynamic adaptation to ultrafiltration and dialysis needs to be studied further.
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PMID:Changes in plasma levels of vasoactive peptides during sequential bicarbonate hemodialysis. 844 69

In patients with advanced liver disease, decreases in renal blood flow, glomerular filtration rate, and urinary output are frequently observed. The deterioration in renal function is usually not due to a unique cause but is the result of the concerted action of several mechanisms operating in parallel; decreased plasma protein formation and increased intrahepatic vascular resistance lead to sequestration of blood volume, favoring hypovolemia and reduction in cardiac output. At the same time enhanced formation of nitroxide leads to peripheral vasodilation; bacterial endotoxin escaping clearance by the diseased liver stimulates the expression of a long-acting nitroxide synthase. Furthermore, vasodilating intestinal mediators such as substance P escape inactivation by the liver. In the face of peripheral vasodilation the maintenance of blood pressure requires an increase in cardiac output, which is achieved by activation of sympathetic nervous tone, renal vasoconstriction, enhanced release of renin, angiotensin, aldosterone, and antidiuretic hormone, leading to renal retention of sodium and water. Renal vasoconstriction is opposed by vasodilatatory prostaglandins, and renal failure may be triggered by inhibition of prostaglandin formation. On the other hand, vasoconstrictive eicosanoids, such as thromboxane B2 and leukotriene E2, which escape hepatic inactivation, may contribute to renal vasoconstriction. Beyond these mechanisms disturbed hepatic regulation of renal function may participate in the generation of hepatorenal syndrome. The liver regulates renal function via both a hepatorenal reflex decreasing renal blood flow and a hypothetical liver-borne diuretic factor increasing renal blood flow. Both enhanced hepatorenal reflex activity and decreased formation of the liver-borne diuretic factor could participate in the pathogenesis of hepatorenal syndrome.
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PMID:New clues to the pathophysiology of hepatorenal failure. 846 32

Blood pressure stability is better during cold hemodialysis (HD). This has mainly been attributed to a more pronounced sympathetic activation during cold than during warm HD. The authors studied the effect of dialysate temperature on vasoactive peptides, noradrenaline (NA), and renin (PRA). Ten hemodynamically stable patients were dialyzed for 240 min with each of two dialysate temperatures: 38.5 degrees C (warm HD = WHD) and 34.5 degrees C (cold HD = CHD). A decrease (P < 0.05) in blood pressure occurred during WHD; however, during CHD, blood pressure was stable. There were no differences in vasoconstrictors between the two regimens. There was a decrease in NA (P < 0.05), a tendency of PRA to increase (NS owing to a large statistical spread), while arginine vasopressin was unchanged. During CHD, there was a small increase in neuropeptide Y (NPY); however, during WHD, NPY only tended to increase. However, the relative NPY levels (percent of baseline levels) after WHD and CHD did not differ. The vasodilator response was similar during both treatments. Calcitonin gene related peptide was unaltered. Motilin tended to decrease initially, but then increased (P < 0.05) to baseline levels. An increase occurred in beta-endorphin (P < 0.05) and substance P(P < 0.01). There was an initial rise (P < 0.05) in vasoactive intestinal peptide (VIP), followed by a tendency to decrease during the remainder of treatment. The authors concluded that blood pressure stability was better during CHD. However, this was not reflected by differences in plasma levels of the vasoactive peptides, nor did they find any difference in the sympathetic drive between the two regimens.
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PMID:Dialysis fluid temperature and vasoactive substances during routine hemodialysis. 855

1. Expression of prostacyclin receptor (IP receptor) mRNA was examined in various mouse organs, and the cells expressing IP receptor mRNA were identified by in situ hybridization studies. Co-localization of mRNA for the IP receptor with that for preprotachykinin A (PPTA), a precursor protein for substance P, with mRNA for the prostaglandin E receptor subtypes (EP1, EP3 and EP4), and with renin mRNA, was examined by double in situ hybridization studies in the dorsal root ganglion and kidney, respectively. 2. IP receptor mRNA was expressed in the thymus and spleen. Expression in the thymus was found exclusively in the medulla, where mature thymocytes expressed transcripts for the IP receptor. Expression in the spleen was found as scattered signals over the white pulp and as punctate signals in the red pulp. The former was found in splenic lymphocytes and the latter in megakaryocytes. 3. IP receptor mRNA was also expressed in the vascular tissues of various organs such as the aorta, coronary arteries, pulmonary arteries and the cerebral arteries, where its expression was confined to smooth muscle cells. No expression was found in veins. In the kidney, IP receptor mRNA was detected in the interlobular arteries and glomerular arterioles but not in the juxtaglomerular (JG) cells which were labelled with the renin mRNA probe. 4. IP receptor mRNA was expressed in about 40% of the neurones in the dorsal root ganglion. Both small- and large-sized neurones were labelled but no labelling was found in the glia. Expression of PPTA mRNA was found in about 30% of total neurones. About 70% of these neurones expressed IP receptor mRNA, and about half of the IP receptor-positive neurones expressed PPTA mRNA. In addition to IP mRNA, mRNAs for EP1, EP3 and EP4 receptors were expressed in about 30%, 50% and 20%, respectively, of the dorsal root ganglion neurones. About 25%, 41% and 24% of the IP receptor-positive neurons co-expressed the EP1, EP3 and EP4 receptor, respectively. 5. These results not only verified IP receptor expression in various cells and tissues known to be sensitive to prostacyclin, but also revealed its expression in other systems, which urges the study of the actions of prostacyclin in these tissues. They also indicated that the actions of prostacyclin on blood vessels and platelets are mediated by the same type of receptor. Absence of IP receptor mRNA in the JG cells suggests that the action of prostacyclin on renin release may be indirect.
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PMID:In situ hybridization studies of prostacyclin receptor mRNA expression in various mouse organs. 868 Jul 13

Endothelins (ETs) were initially thought to be primarily involved in the control of cardiovascular activity, but the presence of ETs and their receptors in a wide variety of other tissues has suggested a much broader range of functions. Specific receptors for ETs are found in nonvascular tissues including neuronal, neuroendocrine, and endocrine cells. In addition, immunoreactive ETs are present in the brain, pituitary, and peripheral endocrine tissues. However, the ET levels in hypothalamo-hypophysial portal and peripheral blood are low, suggesting that the ET system participates in neuroendocrine regulation through paracrine and/or autocrine mechanisms. Both ETA and ETB receptors are expressed in the hypothalamus, adrenal, parathyroid glands, pancreas, ovary, uterus, placenta, and prostate, while only ETA receptors are expressed in GT1 neurons, anterior pituitary cells, alpha T3-1 immortalized gonadotropes, parathyroid-derived cells, thyrocytes, testicular Leydig and Sertoli cells, normal and neoplastic ovarian granulosa cells, chondrocytes, and other cell types. Activation of ET receptors elicits the sequence of cellular events typical of Ca(2+)-mobilizing receptors, with prominent increases in phosphoinositide hydrolysis and elevations of [Ca2+]i that occur in oscillatory and nonoscillatory modes depending on the cell type. ET-induced activation of the phosphoinositide/Ca(2+)- mobilizing pathway in neuronal and endocrine cells is associated with rapid stimulation of secretory responses, including release of gonadotropin-releasing hormone, oxytocin, vasopressin, substance P, atrial natriuretic peptides, gonadotropins, thyrotropin, growth hormone, parathyroid hormone, aldosterone, and catecholamines. On the other hand, ET has inhibitory actions on prolactin, progesterone, and renin release. In addition to stimulating phospholipase C-dependent pathways, ETs also activate phospholipase D-and MAP-kinase-dependent pathways in some of their target cells, as well as expression of early response genes and increased mitogenic activity. In many neuroendocrine cells, ET induces rapid and marked desensitization of its signaling system, in association with extensive internalization of ET receptors and reduced signaling and secretory responses. These findings raise the possibility that ETs participate in the control of secretory responses in the hypothalamo-pituitary system and peripheral endocrine cells, as well as in long-term aspects of regulation in certain neuroendocrine cells.
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PMID:Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells. 881 99

Phase I human studies can be used to differentiate a novel agent from existing drugs that influence the same pathway (eg, angiotensin-converting enzyme [ACE] inhibitors). Human forearm vasculature provides a useful experimental model for such studies because antagonism of local effects of agonists on resistance vasculature can be quantified, unconfounded by reflex cardiovascular responses to systemically applied agonists. In this model, inhibition of ACE with enalapril (given orally) or its active metabolite enalaprilat (given into the brachial artery) influences responses to some, but not all, vasoactive peptides that are substrates of ACE in vitro. Vasoconstrictor responses to angiotensin I (A I) are antagonized, while vasodilator responses to bradykinin are potentiated. Responses to vasoactive intestinal peptide (VIP), substance P (SP), and atrial natriuretic peptide (ANP) are unaltered by ACE inhibition. Vasodilator responses to bradykinin are antagonized by the B2-receptor icatibant and are blunted (but not abolished) by inhibition of the L-arginine/NO pathway with L-NG-monomethyl arginine. In contrast to inhibition of ACE with enalapril, blockade of the AT1 receptor with losartan results in similar inhibition of vasoconstrictor responses to both A I and angiotensin II but has no significant effect on the vasodilator action of bradykinin. The implication is that losartan provides more specific blockade of the renin-angiotensin pathway than does inhibition of ACE. The in vivo methods described in the study confirm the mechanistically relevant differentiation between AT1-receptor antagonism and ACE inhibition in humans.
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PMID:Angiotensin II-receptor (AT1) blockade in the human forearm. 891 43

Increases in arterial pressure and paraventricular nucleus vasopressin release in response to intracerebroventricular injections of angiotensin peptides are blunted in mRen2(27) renin transgenic [TG(+)] rats. Intraventricular injections of tachykinin peptides mimic several of the actions of angiotensin peptides, and angiotensin peptides evoke substance P release from hypothalamic brain slices. The present study assessed whether diminished substance P release occurs in response to angiotensin peptides in TG(+) rats. Systolic blood pressure at 8 to 12 weeks of age averaged 197 +/- 4 mm Hg (n = 20; P < .05) in TG(+) rats compared with 123 +/- 4 mm Hg in normotensive control [TG(-)] rats (n = 18). Body weight was lower in hypertensive than in normotensive rats (305 +/- 14 versus 344 +/- 13 g, respectively; P < .05). Brain slices from hypothalamus were perfused at 37 degrees C with oxygenated Krebs' bicarbonate buffer. Substance P was measured before (basal) and during perfusion with either Krebs' buffer (control) or 2 mumol/L angiotensin-(1-7) or angiotensin II. Basal substance P release was 92 +/- 10 pg/g wet tissue in TG(+) and 98 +/- 12 pg/g in TG(-) rats (P > .05). Angiotensin-(1-7) and angiotensin II significantly increased substance P release from hypothalamus of TG(-) rats (82% and 70% above control: P < .05) but not TG(+) rats. These studies further support the hypothesis that the cardiovascular effects of angiotensin peptides are mediated in part by substance P and that this relationship is blunted in a hypertensive model that results from excess tissue production of angiotensins.
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PMID:Hypothalamic substance P release. Attenuated angiotensin responses in mRen2(27) transgenic rats. 903 51

Head-up tilt testing has become a valuable and widely accepted diagnostic tool for evaluation of patients with vasovagal syncope. This test has afforded clinical researchers the opportunity to focus on the hemodynamic, humoral, and neural changes that accompany syncope. We review the animal and clinical studies that provide insight into the possible pathophysiological mechanisms involved in vasovagal syncope. Hemodynamic measurements in patients with vasovagal syncope suggest that a relative decrease in ventricular size and increase in cardiac contractility may be seen in many patients with vasovagal syncope. Patients with vasovagal syncope have also demonstrated numerous "exaggerated" neurohumoral responses to syncope. Differential changes in plasma levels of epinephrine, renin, endothelin, vasopressin, cortisol, prolactin, beta endorphins, and substance P have been reported by some investigators either prior to or during a syncopal episode in patients with vasovagal syncope. The precise pathophysiological significance of these measurements is unknown at the present time. Measurements of autonomic tone may be accomplished indirectly with analysis of heart rate variability or baroreflex slope, or directly by sympathetic neural recordings of the peroneal nerve. We have demonstrated decreased baroreflex slopes in patients with vasovagal syncope. Using microneurography, we and others have demonstrated decreased sympathetic nerve activity occurring 11 +/- 3 seconds prior to syncope during head-up tilt table testing. A variety of other abnormal reflexes, including blunted forearm blood flow responses during exercise, have been demonstrated by others. These observations suggest that pacing instituted after the event may not be as helpful as the use of a hemodynamic sensor that will result in the initiation of pacing prior to sympathetic withdrawal or modify the decrease in sympathetic tone that occurs prior to syncope.
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PMID:Neural monitoring of vasovagal syncope. 908 May 11


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