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

Matsumoto, Takayuki; Tostes, Rita C.; Webb, R.

doi:10.1152/ajpheart.00084.2011

Cited by 32 publications

(47 citation statements)

References 57 publications

(113 reference statements)

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“…148 Burnstock and Ralevic Up 4 A was enhanced (Matsumoto et al, 2011). P2Y 2 receptor gene haplotypes are associated with essential hypertension in Japanese men (Wang et al, 2010b).…”

Section: A Hypertensionmentioning

confidence: 96%

“…The concentration of Up 4 A, a dinucleotide claimed to be an endothelium-dependent vasoconstrictor, is increased in plasma of juvenile hypertensives and may contribute to the early development of primary hypertension (Jankowski et al, 2007). Up 4 A-induced contractions, mediated by P2X 1 , P2Y 2 , or P2Y 4 receptors, were increased in renal, basilar, and femoral, but not in pulmonary arteries from DOCA-salt hypertensive rats (Matsumoto et al, 2011(Matsumoto et al, , 2012. The authors attributed this to enhanced P2Y signaling in the renal artery, because contractions mediated by P2Y 2 , P2Y 2/4 , and P2Y 6 receptor agonists were also enhanced; there was no change in renal artery protein expression of P2Y 2 , P2Y 4 , and P2Y 6 receptors in DOCAsalt hypertension, but ERK activation stimulated by (Inscho, 2009) and human subcutaneous veins (Lind et al, 1997).…”

Section: A Hypertensionmentioning

confidence: 96%

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Purinergic Signaling and Blood Vessels in Health and Disease

2013

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“…148 Burnstock and Ralevic Up 4 A was enhanced (Matsumoto et al, 2011). P2Y 2 receptor gene haplotypes are associated with essential hypertension in Japanese men (Wang et al, 2010b).…”

Section: A Hypertensionmentioning

confidence: 96%

Section: A Hypertensionmentioning

confidence: 96%

Purinergic Signaling and Blood Vessels in Health and Disease

2013

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“…Increased activation of ERK1/2 in various arteries contributes to augmented vascular contraction and subsequent cardiovascular disease pathologies [30,29]. In addition, we recently demonstrated that the activation of ERK1/2 plays a role in the contractile phenotype modulation of VSMCs [8].…”

Section: Introductionmentioning

confidence: 91%

Activation of Toll-like receptor 3 increases mouse aortic vascular smooth muscle cell contractility through ERK1/2 pathway

Hardigan

Spitler

Matsumoto³

et al. 2015

Pflugers Arch - Eur J Physiol

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Activation of Toll-like receptor 3 (TLR3), a pattern recognition receptor of the innate immune system, is associated with vascular complications. However, whether activation of TLR3 alters vascular contractility is unknown. We, therefore, hypothesized that TLR3 activation augments vascular contractility and activates vascular smooth muscle cell (VSMC) contractile apparatus proteins. Male mice were treated with polyinosinic-polycytidylic acid (Poly I:C group, 14 days), a TLR3 agonist; control mice received saline (vehicle, 14 days). At the end of protocol, blood pressure was measured by tail cuff method. Aortas were isolated and assessed for contractility experiments using a wire myograph. Aortic protein content was used to determine phosphorylated/total interferon regulatory factor 3 (IRF3), a downstream target of TLR3 signaling, and ERK1/2 using Western blot. We investigated the TLR3/IRF3/ERK1/2 signaling pathway and contractile-related proteins such as phosphorylated/total myosin light chain (MLC) and caldesmon (CaD) in aortic VSMC primary cultures. Poly I:C-treated mice exhibited (vs. vehicle-treated mice) (1) elevated systolic blood pressure. Moreover, Poly I:C treatment (2) enhanced aortic phenylephrine-induced maximum contraction, which was suppressed by PD98059 (ERK1/2 inhibitor), and (3) increased aortic levels of phosphorylated IRF3 and ERK1/2. Stimulation of mouse aortic VSMCs with Poly I:C resulted in increased phosphorylation of IRF3, ERK1/2, MLC, and CaD. Inhibition of ERK1/2 abolished Poly I:C-mediated phosphorylation of MLC and CaD. Our data provide functional evidence for the role of TLR3 in vascular contractile events, suggesting TLR3 as a potential new therapeutic target in vascular dysfunction and regulation of blood pressure.

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“…Moreover, other factors such as endothelium-derived hyperpolarizing factor (EDHF) and cyclooxygenase (COX)-mediated substances (prostanoids) are important in the regulation of vascular tone. [19][20][21]24) Indeed, several studies have suggested that 1) vascular responses to extracellular nucleotides/nucleosides are altered in the vasculature of hypertensive individuals, 11,16,29,30) and 2) these endogenous ligand-induced responses are mediated by arterial endothelium-derived factors under various conditions. 13,14,30,31) However, very few studies have investigated the vasorelaxant activity of ATP/ADP/adenosine along with the modulative effects of NO and COX-derived substances on the same arteries in hypertensive individuals.…”

Section: 18)mentioning

confidence: 99%

“…Several studies have suggested that the expression and signaling responses of these receptors is altered under disease conditions. 4,11,[13][14][15][16][17] Moreover, these receptors can mediate a variety of responses to several nucleotides, resulting in the existence of multiple receptors with overlapping ligand preferences. …”

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confidence: 99%

A Comparative Study of Vasorelaxant Effects of ATP, ADP, and Adenosine on the Superior Mesenteric Artery of SHR

Watanabe

Matsumoto

Ando

et al. 2016

Biological & Pharmaceutical Bulletin

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We investigated superior mesenteric arteries from spontaneously hypertensive rats (SHR) to determine the relaxation responses induced by ATP, ADP, and adenosine and the relationship between the relaxant effects of these compounds and nitric oxide (NO) or cyclooxygenase (COX)-derived prostanoids. In rat superior mesenteric artery, relaxation induced by ATP and ADP but not by adenosine was completely eliminated by endothelial denudation. In the superior mesenteric arteries isolated from SHR [vs. age-matched control Wistar Kyoto rats (WKY)], a) ATP-and ADP-induced relaxations were weaker, whereas adenosine-induced relaxation was similar in both groups, b) ATP-and ADP-induced relaxations were substantially and partly reduced by N G -nitro-L-arginine [a NO synthase (NOS) inhibitor], respectively, c) indomethacin, an inhibitor of COX, increased ATP-and ADP-induced relaxations, d) ADP-induced relaxation was weaker under combined inhibition by NOS and COX, and e) adenosine-induced relaxation was not altered by treatment with these inhibitors. These data indicate that levels of responsiveness to these nucleotides/adenosine vary in the superior mesenteric arteries from SHR and WKY and are differentially modulated by NO and COX-derived prostanoids.Key words adenosine; ADP; ATP; relaxation; spontaneously hypertensive rat Extracellular nucleotides and their metabolites including ATP, ADP, and adenosine play pivotal roles in (patho)-physiological processes, including immune responses, inflammation, cardiac fibrosis, atherosclerosis, hypertension, and diabetes.1-10) They also exert a variety of effects on the vasculature, such as platelet activation and alteration in smooth muscle contraction and relaxation, by activating plasmalemmal receptors (e.g., purinoceptors). 1,2,8,11,12) Purinoceptors are classified into two subtypes, namely P1 and P2, based on their pharmacological properties and molecular cloning characteristics.11,12) Adenosine and its phosphates ATP and ADP are endogenous ligands for P1 and P2 receptors, respectively. Several studies have suggested that the expression and signaling responses of these receptors is altered under disease conditions. 4,11,[13][14][15][16][17] Moreover, these receptors can mediate a variety of responses to several nucleotides, resulting in the existence of multiple receptors with overlapping ligand preferences. 11,18)Therefore, it is difficult to understand the effect of nucleotides on vascular function under pathophysiological conditions. Hypertension is a leading risk factor for cardiovascularassociated morbidity and mortality. An important and contributory element in sustained hypertension is an increase in vascular tone, potentially resulting from concurrently reduced relaxation and augmented contraction induced by various endogenous ligands. [19][20][21][22][23][24][25][26] Hypertension-associated vascular dysfunction is partly regulated by endothelium-derived factors. [21][22][23][24] There is a fine balance between endothelium-derived relaxing and contracting factors, a disturba...

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

Cited by 32 publications

References 57 publications

Purinergic Signaling and Blood Vessels in Health and Disease

Purinergic Signaling and Blood Vessels in Health and Disease

Activation of Toll-like receptor 3 increases mouse aortic vascular smooth muscle cell contractility through ERK1/2 pathway

A Comparative Study of Vasorelaxant Effects of ATP, ADP, and Adenosine on the Superior Mesenteric Artery of SHR

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