Uridine adenosine tetraphosphate affects contractility of mouse aorta and decreases blood pressure in conscious rats and mice

Hansen, Pernille; Hristovska, Ana‐Marija; Wolff, H; Vanhoutte, Paul M.; Jensen, Boye L.; Bie, Peter

doi:10.1111/j.1748-1716.2010.02135.x

Cited by 27 publications

(51 citation statements)

References 24 publications

(42 reference statements)

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“…Considering a report that suggested the circulating Up 4 A level is correlated with the left ventricular mass (33) and that DOCA-salt rats exhibit left ventricular hypertrophy, it is possible that the circulating Up 4 A level is increased in DOCA-salt hypertensive rats. With the use of the myograph technique, higher concentrations of Up 4 A (i.e., in the micromolar range) were required to achieve adequate vasoconstriction (even though Up 4 A sensitivity is increased in RA rings from DOCA-salt rats), and this is consistent with previous reports using other arterial rings in the myograph system (23,24,41). The discrepancy between these studies may be explained by differences between these methodologies.…”

Section: Discussionsupporting

confidence: 57%

“…Although Up 4 A has been characterized as a potent constrictor in rat aorta (41), rat pulmonary arteries (23), rat perfused kidney (35,58), mouse aorta (24), and mouse renal afferent arterioles (34), there are no studies on its vascular effects in vessels from animals with vascular disease. The present study is the first to show enhancement of Up 4 A-induced contraction in RA in a salt-dependent model of hypertension, the DOCA-salt rats.…”

Section: Discussionmentioning

confidence: 99%

“…Up 4 A is also the first dinucleotide found in living organisms that contains both purine and pyrimidine moieties, which are known to potentially activate both P2X and P2Y receptors. In the last five years since the identification of Up 4 A (35), several reports have indicated that Up 4 A modulates vascular tone in rat aorta (41), rat pulmonary arteries (23), mouse renal afferent arterioles (34), and mouse aorta (24). Moreover, Jankowski et al (35) found that in isolated perfused kidney, Up 4 A stimulated vasoconstriction mainly through P2X 1 receptors and probably also through P2Y 2 and P2Y 4 receptors.…”

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Uridine adenosine tetraphosphate-induced contraction is increased in renal but not pulmonary arteries from DOCA-salt hypertensive rats

Matsumoto

Tostes

Webb

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Matsumoto T, Tostes RC, Webb RC. Uridine adenosine tetraphosphate-induced contraction is increased in renal but not pulmonary arteries from DOCA-salt hypertensive rats. Am J Physiol Heart Circ Physiol 301: H409 -H417, 2011. First published May 6, 2011 doi:10.1152/ajpheart.00084.2011.-Uridine adenosine tetraphosphate (Up 4A) was reported as a novel endothelium-derived contracting factor. Up 4A contains both purine and pyrimidine moieties, which activate purinergic (P2)X and P2Y receptors. However, alterations in the vasoconstrictor responses to Up 4A in hypertensive states remain unclear. The present study examined the effects of Up 4A on contraction of isolated renal arteries (RA) and pulmonary arteries (PA) from DOCA-salt rats using isometric tension recording. RA from DOCAsalt rats exhibited increased contraction to Up 4A versus arteries from control uninephrectomized rats in the absence and presence of N Gnitro-L-arginine (nitric oxide synthase inhibitor). On the other hand, the Up 4A-induced contraction in PA was similar between the two groups. Up 4A-induced contraction was inhibited by suramin (nonselective P2 antagonist) but not by diinosine pentaphosphate pentasodium salt hydrate (Ip 5I; P2X1 antagonist) in RA from both groups. Furthermore, 2-thiouridine 5=-triphosphate tetrasodium salt (2-Thio-UTP; P2Y 2 agonist)-, uridine-5=-(␥-thio)-triphosphate trisodium salt (UTP␥S; P2Y 2/P2Y4 agonist)-, and 5-iodouridine-5=-O-diphosphate trisodium salt (MRS 2693; P2Y 6 agonist)-induced contractions were all increased in RA from DOCA-salt rats. Protein expression of P2Y 2-, P2Y4-, and P2Y6 receptors in RA was similar between the two groups. In DOCA-salt RA, the enhanced Up 4A-induced contraction was reduced by PD98059, an ERK pathway inhibitor, and Up 4A-stimulated ERK activation was increased. These data are the first to indicate that Up 4A-induced contraction is enhanced in RA from DOCA-salt rats. Enhanced P2Y receptor signaling and activation of the ERK pathway together represent a likely mechanism mediating the enhanced Up 4A-induced contraction. Up4A might be of relevance in the pathophysiology of vascular tone regulation and renal dysfunction in arterial hypertension. extracellular nucleotide; ERK; purinoceptor EXTRACELLULAR NUCLEOTIDES contribute to the local regulation of vascular tone and play important roles in pathophysiological processes, including hypertension, diabetes, atherosclerosis, and remodeling (7,9,16). In blood vessels, nucleotides, such as ATP and UTP, can be released from platelets or from adventitial nerves and endothelial cells to induce either vasoconstriction or vasodilation through cell surface purinergic (P2) receptors (1,8,15).P2 receptors for nucleotides belong to two major families: ionotropic P2X receptors and metabotropic P2Y receptors (1,8,15). Several reports demonstrated that these purinoceptors are expressed in renal and pulmonary vascular beds (12,25,31,38,52,53), contributing to the physiology of these specialized organ systems (4,22,30). However, the involvement of these pu...

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Uridine adenosine tetraphosphate-induced contraction is increased in renal but not pulmonary arteries from DOCA-salt hypertensive rats

Matsumoto

Tostes

Webb

2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…Up 4 A induces pulmonary arterial SM contraction through activation of suramin-sensitive P2Y receptors (12). Up 4 A-induced SM contraction was also reported in rat aortic SM (13,14) and human airway SM (15). Furthermore, elevated concentrations of Up 4 A were detected in juvenile hypertensive patients (16).…”

Section: Introductionmentioning

confidence: 82%

Uridine adenosine tetraphosphate induces contraction of circular and longitudinal gastric smooth muscle by distinct signaling pathways

Yuan

Wang

et al. 2013

IUBMB Life

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Extracellular nucleotides uridine-5 0 -triphosphate (UTP) and adenosine-5 0 -triphosphate (ATP) induce contraction of gastric smooth muscle (SM). The dinucleotide uridine adenosine tetraphosphate (Up 4 A), an endothelium-derived contraction factor, induces vascular SM contraction. Its effect on gastric SM contractions, however, is unknown. We addressed the hypothesis that Up 4 A induces gastric SM contraction via a mechanism that may differ between circular and longitudinal muscle (CM and LM, respectively). CM and LM were isolated from rat gastric fundus for the measurement of isometric tension. Up 4 A induced transient contractile responses in both CM and LM, which were similar to those induced by ATP and UTP. Up 4 A failed to induce contraction of either LM or CM in the absence of extracellular Ca 21 or in the presence of nimodipine, an inhibitor of voltagegated Ca 21 channels. P2X1, 2, 4, 5 and 7 and P2Y1, 2, 4 and 6 receptor expression was detected in gastric SM by reverse transcription-polymerase chain reaction. IP 5 I (a P2X receptor antagonist) and a,b-methylene-ATP (a P2X receptor agonist) had no effect on Up 4 Ainduced contractions of either LM or CM, and a,b-methylene-ATP alone failed to induce a contractile response in either tissue. Suramin (a P2Y receptor antagonist), on the other hand, significantly inhibited Up 4 A-induced contraction of CM, but not LM. Up 4 Ainduced contraction of CM, but not LM, was also inhibited by pretreatment with Y-27632, an inhibitor of Rho-associated kinase. We conclude that Up 4 A induces extracellular Ca 21 -dependent contractions of rat gastric LM and CM, and Up 4 A-induced contraction of CM is mediated by suramin-sensitive P2Y receptors and subsequent activation of the Rho-associated kinase pathway. V C 2013 IUBMB Life, 65(7): [623][624][625][626][627][628][629][630][631][632] 2013

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“…Nonetheless, the existence of dinucleoside polyphosphates in the plasma and blood (Luthje and Ogilvie, 1988), also suggested an effect on vasoconstriction or/and vasodilation. When analysing the effect of the vascular tone, dinucleoside polyphosphates such as Ap 4 U produces a biphasic effect although the predominant one at low concentrations is vasoconstriction, infusions of this dinucleotide elicit hypotension and electrolyte retention (Flores et al, 1999;Hansen et al, 2010).…”

Section: Presence and Extracellular Actions Of Dinucleoside Polyphospmentioning

confidence: 99%

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

Carracedo

Crooke

Guzmán-Aránguez

et al. 2016

Progress in Retinal and Eye Research

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a b s t r a c tDinucleoside polyphosphates comprises a group of dinucleotides formed by two nucleosides linked by a variable number of phosphates, abbreviated NpnN (where n represents the number of phosphates). These compounds are naturally occurring substances present in tears, aqueous humour and in the retina. As the consequence of their presence, these dinucleotides contribute to many ocular physiological processes. On the ocular surface, dinucleoside polyphosphates can stimulate tear secretion, mucin release from goblet cells and they help epithelial wound healing by accelerating cell migration rate. These dinucleotides can also stimulate the presence of proteins known to protect the ocular surface against microorganisms, such as lysozyme and lactoferrin. One of the latest discoveries is the ability of some dinucleotides to facilitate the paracellular way on the cornea, therefore allowing the delivery of compounds, such as antiglaucomatous ones, more easily within the eye. The compound Ap 4 A has been described being abnormally elevated in patient's tears suffering of dry eye, Sjogren syndrome, congenital aniridia, or after refractive surgery, suggesting this molecule as biomarker for dry eye condition. At the intraocular level, some diadenosine polyphosphates are abnormally elevated in glaucoma patients, and this can be related to the stimulation of a P2Y 2 receptor that increases the chloride efflux and water movement in the ciliary epithelium. In the retina, the dinucleotide dCp 4 U, has been proven to be useful to help in the recovery of retinal detachments. Altogether, dinucleoside polyphosphates are a group of compounds which present relevant physiological actions but which also can perform promising therapeutic benefits.

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Uridine adenosine tetraphosphate affects contractility of mouse aorta and decreases blood pressure in conscious rats and mice

Abstract: up(4) A has direct biphasic effects on vascular smooth muscle of the mouse aorta but vasoconstriction dominates at low concentrations. In conscious rodents, step-up infusions of Up(4) A elicit hypotension and electrolyte retention.

Cited by 27 publications

References 24 publications

Uridine adenosine tetraphosphate-induced contraction is increased in renal but not pulmonary arteries from DOCA-salt hypertensive rats

Uridine adenosine tetraphosphate-induced contraction is increased in renal but not pulmonary arteries from DOCA-salt hypertensive rats

Uridine adenosine tetraphosphate induces contraction of circular and longitudinal gastric smooth muscle by distinct signaling pathways

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

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