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Mitsuo Iida - One of the best experts on this subject based on the ideXlab platform.
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Role of ERK and Rho kinase pathways in central pressor action of Urotensin II.
Journal of hypertension, 2004Co-Authors: Yingzi Lin, Takuya Tsuchihashi, Kiyoshi Matsumura, Masayo Fukuhara, Koji Fujii, Mitsuo IidaAbstract:BACKGROUND It has been shown that central Urotensin II acts on the central nervous system to increase arterial pressure in conscious rats. OBJECTIVE To investigate the intracellular signal transduction mechanisms of the central cardiovascular action of Urotensin II. METHODS The effects of intracerebroventricular (i.c.v.) administration of the extracellular signal-regulated protein kinase (ERK) inhibitor, PD 98059 (20 nmol), the phosphatidylinositol 3 (PI3) kinase inhibitor, wortmannin (20 nmol), or the Rho kinase inhibitor, Y-27632 (20 nmol), on cardiovascular responses to i.c.v. Urotensin II (10 nmol) were determined in conscious rats. RESULTS I.c.v. injection of Urotensin II increased both arterial pressure and heart rate (14.9 +/-1.5 mmHg and 94.6 +/-12.8 beats/min, respectively; P < 0.05 for each). Pretreatment with PD 98059 or Y-27632 significantly (P < 0.01 and P < 0.05, respectively) attenuated the pressor response induced by i.c.v. Urotensin II (6.6 +/-1.4 and 6.9 +/-1.2 mmHg, respectively). Pretreatment with a mixed solution of PD 98059 and Y-27632 failed to cause further suppression of the Urotensin II-induced pressor responses (4.5 +/-0.9 mmHg). In contrast, pretreatment with i.c.v. wortmannin failed to influence the pressor response induced by i.c.v. Urotensin II (12.6 +/-1.3 mmHg). The tachycardiac response induced by i.c.v. Urotensin II was not influenced by pretreatment with PD 98059, Y-27632 or wortmannin. CONCLUSIONS These findings suggest that the ERK and Rho kinase pathways, but not the PI3 pathway, may be involved in the central pressor action of Urotensin II in conscious rats.
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Central cardiovascular action of Urotensin II in conscious rats.
Journal of hypertension, 2003Co-Authors: Yingzi Lin, Takuya Tsuchihashi, Kiyoshi Matsumura, Isao Abe, Mitsuo IidaAbstract:OBJECTIVE To examine the central cardiovascular action of Urotensin II in conscious rats. METHODS Intracerebroventricular (ICV) injections of Urotensin II (1 and 10 nmol) were carried out in conscious Wistar rats. The effects of intravenous (i.v.) Urotensin II (10 nmol) were also determined. RESULTS The ICV injection of Urotensin II at a dose of 1 nmol did not alter the arterial pressure or heart rate significantly, while 10 nmol Urotensin II increased the arterial pressure and heart rate. The mean arterial pressure at 5 min of ICV Urotensin II was 121 +/- 4 mmHg, which was significantly higher than that obtained by ICV injection of artificial cerebrospinal fluid (107 +/- 3 mmHg, P
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Central cardiovascular action of Urotensin II in spontaneously hypertensive rats.
Hypertension research : official journal of the Japanese Society of Hypertension, 2003Co-Authors: Yingzi Lin, Takuya Tsuchihashi, Kiyoshi Matsumura, Masayo Fukuhara, Koji Fujii, Yusuke Ohya, Mitsuo IidaAbstract:We have previously reported that Urotensin II acts on the central nervous system to increase blood pressure in normotensive rats. In the present study, we have determined the central cardiovascular action of Urotensin II in spontaneously hypertensive rats (SHR). Intracerebroventricular (ICV) injection of Urotensin II elicited a dose-dependent increase in blood pressure in both SHR and normotensive Wistar-Kyoto rats (WKY). The changes in mean arterial pressure induced by ICV Urotensin II at doses of 1 and 10 nmol in the WKY were 8±2 and 23±3 mmHg, respectively. ICV administration of Urotensin II caused significantly greater increases in blood pressure in SHR (16±3 mmHg at 1 nmol and 35±3 mmHg at 10 nmol, respectively) compared with those in WKY. Urotensin II (10 nmol) elicited significant and comparable increases in heart rate in SHR (107±10 bpm) and WKY (101±21 bpm). Plasma epinephrine concentrations after ICV administration of 10 nmol Urotensin II were 203±58 pmol/ml in SHR and 227±47 pmol/ml in WKY, which tended to be higher than those in artificial cerebrospinal fluid-injected rats (73±7 and 87±28 pmol/ml, respectively, p
Stephen R Grant - One of the best experts on this subject based on the ideXlab platform.
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Urotensin II-induced signaling involved in proliferation of vascular smooth muscle cells
Vascular health and risk management, 2010Co-Authors: Myriam Iglewski, Stephen R GrantAbstract:The Urotensin II receptor, bound by the ligand Urotensin II, generates second messengers, ie, inositol triphosphate and diacylglycerol, which stimulate the subsequent release of calcium (Ca2+) in vascular smooth muscle cells. Ca2+ influx leads to the activation of Ca2+-dependent kinases (CaMK) via calmodulin binding, resulting in cellular proliferation. We hypothesize that Urotensin II signaling in pulmonary arterial vascular smooth muscle cells (Pac1) and primary aortic vascular smooth muscle cells (PAVSMC) results in phosphorylation of Ca2+/calmodulin-dependent kinases leading to cellular proliferation. Exposure of Pac1 cultures to Urotensin II increased intracellular Ca2+, subsequently activating Ca2+/calmodulin-dependent kinase kinase (CaMKK), and Ca2+/calmodulin-dependent kinase Type I (CaMKI), extracellular signal-regulated kinase (ERK 1/2), and protein kinase D. Treatment of Pac1 and PAVSMC with Urotensin II increased proliferation as measured by 3H-thymidine uptake. The Urotensin II-induced increase in 3H-thymidine incorporation was inhibited by a CaMKK inhibitor. Taken together, our results demonstrate that Urotensin II stimulation of smooth muscle cells leads to a Ca2+/calmodulin-dependent kinase-mediated increase in cellular proliferation.
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Urotensin II-induced signaling involved in proliferation of vascular smooth muscle cells
Dove Medical Press, 2010Co-Authors: Myriam Iglewski, Stephen R GrantAbstract:Myriam Iglewski, Stephen R GrantDepartment of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, Texas, USAAbstract: The Urotensin II receptor, bound by the ligand Urotensin II, generates second ­messengers, ie, inositol triphosphate and diacylglycerol, which stimulate the subsequent release of calcium (Ca2+) in vascular smooth muscle cells. Ca2+ influx leads to the activation of Ca2+-dependent kinases (CaMK) via calmodulin binding, resulting in cellular proliferation. We hypothesize that Urotensin II signaling in pulmonary arterial vascular smooth muscle cells (Pac1) and primary aortic vascular smooth muscle cells (PAVSMC) results in phosphorylation of Ca2+/calmodulin-dependent kinases leading to cellular proliferation. Exposure of Pac1 cultures to Urotensin II increased intracellular Ca2+, subsequently activating Ca2+/calmodulin-dependent kinase kinase (CaMKK), and Ca2+/calmodulin-dependent kinase Type I (CaMKI), extracellular signal-regulated kinase (ERK 1/2), and protein kinase D. Treatment of Pac1 and PAVSMC with Urotensin II increased proliferation as measured by 3H-thymidine uptake. The Urotensin II-induced increase in 3H-thymidine incorporation was inhibited by a CaMKK inhibitor. Taken together, our results demonstrate that Urotensin II stimulation of smooth muscle cells leads to a Ca2+/calmodulin-dependent kinase-mediated increase in cellular proliferation.Keywords: Urotensin II receptor, CaMKI, hypertrophy, CaMKK, protein kinase
Hubert Vaudry - One of the best experts on this subject based on the ideXlab platform.
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Occurrence of two distinct Urotensin II-related peptides in zebrafish provides new insight into the evolutionary history of the Urotensin II gene family.
Endocrinology, 2011Co-Authors: Caroline Parmentier, Hubert Vaudry, Emilie Hameury, Christophe Dubessy, Feng B. Quan, Damien Habert, André Calas, Isabelle Lihrmann, Hervé TostivintAbstract:The UII gene family possesses four distinct paralogs that arose during two rounds of tetraploidization: Urotensin II, Urotensin II-related peptide (URP) and the two novel teleost isoforms URP1 and URP2.
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Urotensin II receptor and acetylcholine release from mouse cervical spinal cord nerve terminals
Neuroscience, 2010Co-Authors: Federica Bruzzone, Chiara Cervetto, Maria Chiara Mazzotta, Paolo Bianchini, Emiliano Ronzitti, Jérôme Leprince, Alberto Diaspro, Guido Maura, Mauro Vallarino, Hubert VaudryAbstract:Abstract Accumulating evidence indicate that the neuropeptide Urotensin II and Urotensin II receptors are expressed in subsets of mammal spinal motoneurons. In fact, a role for the peptide in the regulation of motoneuron function at neuromuscular junction has been suggested, while roles for Urotensin II at central synapses in spinal cord have never been addressed. We found that Urotensin II receptors were closely associated with cholinergic terminals apposed to a subset of motoneuron and non-motoneuron cell bodies in the ventral horn of the adult mouse cervical spinal cord; Urotensin II receptor was also expressed on non-cholinergic nerve terminals. In particular, Urotensin II receptor appeared associated with both large cholinergic C-boutons and standard cholinergic terminals contacting some motoneuron perikarya. Cholinergic nerve terminals from mouse cervical spinal cord were equipped with functional presynaptic Urotensin II receptors linked to excitation of acetylcholine release. In fact, functional experiments conducted on cervical spinal synaptosomes demonstrated a Urotensin II evoked calcium-dependent increase in [3H]acetylcholine release pharmacologically verified as consistent with activation of Urotensin II receptors. In spinal cord these actions would facilitate cholinergic transmission. These data indicate that, in addition to its role at the neuromuscular junction, Urotensin II may control motor function through the modulation of motoneuron activity within the spinal cord.
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Cardiovascular actions of frog Urotensin II in the frog, Rana catesbeiana.
General and comparative endocrinology, 1995Co-Authors: Kenji Yano, Hubert Vaudry, James W. Hicks, J. Michael ConlonAbstract:The effects of synthetic frog Urotensin II on cardiac output and arterial blood pressure and on the motility of isolated vascular smooth muscle were investigated in the bullfrog, Rana catesbeiana. Bolus injections of frog Urotensin II (100 nmol/kg) into the left systemic arch produced a rapid and sustained fall in blood flow through the right branch of the truncus arteriosus (to 62 +/- 5% of preinjection values; n = 8). The response exhibited strong tachyphylaxis. There were no significant effects on heart rate and central arterial blood pressure but the fact that a fall in cardiac output was not accompanied by a fall in pressure suggests that the peptide produced an increase in peripheral vascular resistance. Rings of vascular smooth muscle from the proximal and distal regions of the left and right systemic arches responded to Urotensin II with sustained and concentration-dependent contractions. The tissues from the different regions did not significantly differ in their maximum response and sensitivity to the peptide (EC50 values from 4.6 x 10(-9) to 6.5 x 10(-9) M; n = 6). Acetylcholine (3 x 10(-8) to 3 x 10(-6) M) significantly (P < 0.05) relaxed the rings in an endothelium-dependent manner but Urotensin II did not produce relaxation at any concentration tested. The contractile effect of Urotensin II (10(-7) M) was not affected by preincubation of the rings with atropine, tetrodotoxin, and somatostatin-14 but indomethacin produced a significant (P < 0.05) decrease in the amplitude of the contractions of the systemic arch (to 18 +/- 2% of control values; n = 6). Arachidonic acid (10(-5) M) also produced a sustained contraction of the rings. The data suggest an involvement of prostaglandin synthesis in the contractile action of Urotensin II on isolated frog vascular smooth muscle but, unlike in mammals, Urotensin II does not stimulate nitric oxide synthesis in this tissue.
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In vitro study of the effect of Urotensin II on corticosteroid secretion in the frog Rana ridibunda.
The Journal of steroid biochemistry and molecular biology, 1994Co-Authors: Marc G. J. Feuilloley, J. M. Conlon, Howard A. Bern, Olivier Lesouhaitier, Catherine Delarue, S. De Marchis, Hubert VaudryAbstract:Abstract Urotensin II is a cyclic dodecapeptide that was originally isolated from the fish urophysis, the terminus of a neurosecretory system located in the caudal area of the spinal cord. We have recently isolated and characterized Urotensin II in the brain of a tetrapod, the frog Rana ridibunda . Recent reports, suggesting that Urotensin II may stimulate cortisol secretion in fish, prompted us to investigate the possinle effects of fish and frog Urotensin II on corticosteroid secretion in amphibians. Exposure of perifused frog adrenal slices to goby ( Gillichthys mirabilis ) urophysis extracts induced a marked stimulation of corticosterone and aldosterone secretion. In contrast, at concentrations ranging from 10 −10 to 10 −6 M, synthetic goby Urotensin II had no effect on corticosteroid production. Similarly, infusion of synthetic frog Urotensin II (10 −10 to 10 −6 M) did not modify the spontaneous release of corticosterone and aldosterone. In addition, frog Urotensin II had no effect in ACTH- and angiotensin II-induced secretion of corticosteroids. These results show that in frog, Urotensin II does not modulate spontaneous and ACTH- or angiotensin II-evoked adrenal steroidogenesis.
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Spasmogenic actions of frog Urotensin II on the bladder and ileum of the frog, Rana catesbeiana.
General and comparative endocrinology, 1994Co-Authors: Kenji Yano, Hubert Vaudry, J. Michael ConlonAbstract:The effects of synthetic frog Urotensin II on the motility of isolated smooth muscle strips of urinary bladder and ileum from the bullfrog Rana catesbeiana were investigated. The strips of bladder exhibited strong spontaneous contractions. Frog Urotensin II produced a concentration-dependent increase in the frequency of contraction (EC50 = 8.1 × 10-9M) but had no significant effect on tension. Maximum stimulation (4 times the rate of spontaneous contractions) was produced by 10-7M peptide. The ileal smooth muscle strips exhibited only weak spontaneous contractions but frog Urotensin II produced concentration-dependent increases in both the frequency (EC50 = 1.3 × 10-9M) and the strength (EC50 = 3.6 × 10-9M) of contraction. The peptide had no effect on the motility of strips of rat urinary bladder and ileum. In both the frog bladder and ileum preparations, the effect of Urotensin II was not affected by preincubation of the strips with atropine, tetrodotoxin, and somatostatin-14 but indomethacin produced a significant (P < 0.05) decrease in the strength of the contractions of the bladder (to 21 ± 6% of control values) and ileum (to 32 ± 13%). Arachidonic acid produced an increase in the frequency of contraction of the bladder and an increase in both the frequency and the strength of contraction of the ileum. The data demonstrate that Urotensin II exercises a spasmogenic effect on amphibian smooth muscle that is similar to that of the peptide on teleost tissues. An involvement of prostaglandin synthesis in the spasmogenic action of Urotensin II on frog bladder and ileum is indicated.
J. M. Conlon - One of the best experts on this subject based on the ideXlab platform.
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Rainbow trout (Oncorhynchus mykiss) Urotensin-I: structural differences between Urotensins-I and urocortins.
General and comparative endocrinology, 1999Co-Authors: D. Baršyt, J. M. Conlon, D.r. Tipping, D. Smart, Bridget I. Baker, David A. LovejoyAbstract:Abstract In bony fishes, both corticotropin-releasing factor (CRF) and Urotensin-I play a role in the regulation of interrenal glucocorticoid release. The rainbow trout, Oncorhynchus mykiss, is a useful model for understanding the mechanisms of stress and the hypothalamo–pituitary–interrenal axis because of its phylogenetic position at the base of the euteleostei and its popularity as a food fish. Urotensin-I may act as a glucocorticoid releaser in a mechanism phylogenetically older than that of CRF. The structural and functional relationships of trout Urotensin-I have been investigated. The transcript was cloned from a trout brain hypothalamic cDNA library. A single positive clone was isolated and sequenced. It possesses 3218 bases and has the longest 3′ untranslated region of all Urotensins-I and CRF transcripts found to date. In comparison to the other fish orthologues, it has the closest sequence identity to the mammalian urocortins. The transcript appears to be differentially processed in brain and urophysis as determined by Northern blot analysis and the presence of polyadenylation signals in the 3′ untranslated region. Synthetic trout Urotensin-I activated both human CRF-R1 and -R2 receptor-transfected CHO cells with a potency similar to that of white sucker ( Catostomus commersoni ) Urotensin-I. Both fish neuropeptides possessed an order of magnitude less potency than human urocortin in CRF-R2 transfected cells.
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Urotensin ii from the river lamprey lampetra fluviatilis the sea lamprey petromyzon marinus and the paddlefish polyodon spathula
General and Comparative Endocrinology, 1995Co-Authors: David Waugh, Steven D Mims, Stacia A Sower, John H. Youson, J. M. ConlonAbstract:Abstract Urotensin II was isolated from extracts of the whole brain of the river lamprey (Lampetra fluviatilis) and the sea lamprey (Petromyzon marinus). The primary structure of the peptide from both species is the same (Asn-Asn-Phe-Ser-Asp-Cys-Phe-Trp-Lys-Tyr-Cys-Val) and this amino acid sequence is identical to that of Urotensin II from the dogfish and skate. Consistent with previous morphological studies indicating that the Agnatha lack a caudal neurosecretory system, Urotensin II was not detected in an extract of P. marinus spinal cord. The data suggest that the Urotensin II may have functioned in the earliest vertebrates as a neurotransmitter/neuromodulator in the central nervous system rather than as a neurohormone of the caudal neurosecretory system. Urotensin II was also isolated from an extract of the spinal cord of a chondrostean fish, the paddlefish (Polyodon spathula). The primary structure of the paddlefish Urotensin II (Gly-Ser-Thr-Ser-Glu-Cys-Phe-Trp-Lys-Tyr-Cys-Val) is the same as that of another chondrostean, the sturgeon (Acipenser ruthenus). The study provides further evidence for a widespread distribution of Urotensin II in vertebrate species and suggests that the primary structure of the peptide is better conserverd in these phylogenetically ancient fish than in teleosts.
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In vitro study of the effect of Urotensin II on corticosteroid secretion in the frog Rana ridibunda.
The Journal of steroid biochemistry and molecular biology, 1994Co-Authors: Marc G. J. Feuilloley, J. M. Conlon, Howard A. Bern, Olivier Lesouhaitier, Catherine Delarue, S. De Marchis, Hubert VaudryAbstract:Abstract Urotensin II is a cyclic dodecapeptide that was originally isolated from the fish urophysis, the terminus of a neurosecretory system located in the caudal area of the spinal cord. We have recently isolated and characterized Urotensin II in the brain of a tetrapod, the frog Rana ridibunda . Recent reports, suggesting that Urotensin II may stimulate cortisol secretion in fish, prompted us to investigate the possinle effects of fish and frog Urotensin II on corticosteroid secretion in amphibians. Exposure of perifused frog adrenal slices to goby ( Gillichthys mirabilis ) urophysis extracts induced a marked stimulation of corticosterone and aldosterone secretion. In contrast, at concentrations ranging from 10 −10 to 10 −6 M, synthetic goby Urotensin II had no effect on corticosteroid production. Similarly, infusion of synthetic frog Urotensin II (10 −10 to 10 −6 M) did not modify the spontaneous release of corticosterone and aldosterone. In addition, frog Urotensin II had no effect in ACTH- and angiotensin II-induced secretion of corticosteroids. These results show that in frog, Urotensin II does not modulate spontaneous and ACTH- or angiotensin II-evoked adrenal steroidogenesis.
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Cardiovascular actions of dogfish Urotensin II in the dogfish Scyliorhinus canicula
American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 1993Co-Authors: Neil Hazon, C. Bjenning, J. M. ConlonAbstract:Bolus injections of synthetic dogfish Urotensin II (0.1-1.0 nmol) into the celiac artery of the conscious dogfish Scyliorhinus canicula (n = 8) resulted in sustained and dose-dependent increases in arterial blood pressure and pulse pressure. A maximum rise in mean arterial pressure of 10.5 +/- 1.2 mmHg (equivalent to 38.6 +/- 4.2% over mean basal values) and a maximum increase in pulse pressure of 3.9 +/- 0.8 mmHg was elicited by injection of 0.5 nmol of peptide. In comparison, a bolus injection of epinephrine (5 nmol) elicited a rise of 24.8 +/- 3.3% in mean arterial pressure. Bolus injection of 0.5 nmol synthetic goby (Gillichthys mirabilis) Urotensin II under the same conditions did not elicit a significant hypertensive response. When dogfish Urotensin II (0.5 nmol) was administered 3 min after an intra-arterial injection of phentolamine, the rise in arterial blood pressure was completely abolished. Dogfish Urotensin II produced a dose-dependent contraction (pD2 = 6.58 +/- 0.07; n = 8) of isolated rings of vascular muscle prepared from the first afferent branchial artery of the dogfish. A maximum contractile force of 1.3 mN was produced by 10(-5) M peptide. The Urotensin II-induced contraction of the vascular rings was unaffected by pretreatment with tetrodotoxin (1 microM) or indomethacin (14 microM). It is concluded that Urotensin II has potent hypertensive activity in the dogfish that is mediated, at least in part, through release of catecholamines, but the sustained nature of the pressor response suggests that the peptide may have a direct action on the heart.
Ian B. Wilkinson - One of the best experts on this subject based on the ideXlab platform.
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The effects of Urotensin II and urantide on forearm blood flow and systemic haemodynamics in humans.
British journal of clinical pharmacology, 2009Co-Authors: Joseph Cheriyan, Timothy J. Burton, Timothy J. Bradley, Sharon M.l. Wallace, Kaisa M. Mäki-petäjä, Isla S. Mackenzie, Carmel M. Mceniery, John Brown, Ian B. WilkinsonAbstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • In vitro studies have shown that Urotensin II is a potent arterial vasoconstrictor. • Previous studies investigating the in vivo cardiovascular actions of intra-arterial administration of Urotensin II in humans have provided conflicting results. • The cardiovascular actions of intra-arterial administration of the Urotensin II receptor antagonist, urantide, are unknown. WHAT THIS STUDY ADDS • We have shown no in vivo effect of Urotensin II or urantide on human forearm resistance vessels. • Previous study discrepancies do not seem to relate to either the age or cardiovascular disease (CVD) status of subjects. AIMS (i) To compare the effects of intra-arterial administration of Urotensin II in patients with CVD with healthy volunteers, and (ii) to study the haemodynamic effects of intra-arterial infusion of the Urotensin II receptor antagonist, urantide. METHODS Ten healthy volunteers and 10 patients with CVD received a dose-ramped brachial artery infusion of Urotensin II. A further six healthy male volunteers received a prolonged Urotensin II infusion and 11 healthy male volunteers received a dose-ramped infusion of urantide. Forearm blood flow (FBF) was measured every 20 min and blood pressure and heart rate were assessed every 20 min. RESULTS In healthy volunteers and patients with CVD, intra-arterial infusion of Urotensin II had no effect on FBF ratio. A dose-ramped infusion of urantide similarly had no effect on FBF ratio. During dose-ramped infusions of Urotensin II and urantide, systolic and mean arterial blood pressure increased significantly. In healthy volunteers, Urotensin II and urantide, respectively, increased systolic blood pressure from 133 ± 6 to 137 ± 5 mmHg (P < 0.01) and from 113 ± 4 to 120 ± 4 mmHg (P < 0.01). In patients with CVD, heart rate also significantly increased during dose-ramped infusion of Urotensin II from 59 ± 3 to 62 ± 4 bpm (P < 0.05). CONCLUSIONS We have shown no in vivo effect of Urotensin II or urantide on human forearm resistance vessels. Previous discrepancies do not seem to relate to either the age or CVD status of subjects. Changes in systemic cardiovascular haemodynamics during the dose-ramped infusion studies are unlikely to be caused by Urotensin II receptor modulation.
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No effect on central or peripheral blood pressure of systemic Urotensin II infusion in humans
British journal of clinical pharmacology, 2002Co-Authors: Jonathan T. Affolter, Richard J. Balment, Ian B. Wilkinson, David E. Newby, Matthew J. Winter, David J. WebbAbstract:Aims In rodent and primate studies, Urotensin II is an extremely potent vasoconstrictor peptide with effects in the central aortic and arterial vasculature as well as on cardiac function. The aim of the present study was to assess systemic haemodynamic responses to intravenous Urotensin II infusion in humans. Methods In 10 healthy male volunteers, intravenous Urotensin II (3, 30 and 300 pmol min−1) and saline placebo were given on separate occasions in a single-blind randomized manner. Systemic haemodynamics and arterial stiffness were assessed by sphygmomanometry, transthoracic bioimpedance, and pulse wave analysis. Plasma Urotensin II immuno-reactivity was measured by radio-immunoassay. Results Intravenous Urotensin II infusions were well tolerated with no adverse clinical effects and no electrocardiographic changes. Circulating plasma Urotensin II immuno-reactivity increased from baseline of 16 ± 1 to 1460 ± 82 pmol l−1 (mean ± s.e. mean) during infusion of Urotensin II at 300 pmol min−1 (P
