Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats

Mukohda, Masashi; Okada, Muneyoshi; Hara, Yukio; Yamawaki, Hideyuki

doi:10.1254/jphs.12088fp

Cited by 32 publications

(26 citation statements)

References 33 publications

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“…Because previous reports demonstrated that NO-mediated endothelium-dependent relaxation was impaired in the artery from SHR [6,11,12], this observation may support the idea that the effect of omentin was endothelial NOdependent. However, since our previous results suggested the NO-independent component of vasodilation by omentin in isolated blood vessel [15], we cannot completely exclude the possibility that omentin may reduce the agonists-induced increases in BP via NO-independent mechanisms.…”

Section: Discussionsupporting

confidence: 74%

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A Novel Adipocytokine, Omentin, Inhibits Agonists-Induced Increases of Blood Pressure in Rats

Kazama

Okada

Hara

et al. 2013

The Journal of Veterinary Medical Science

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ABSTRACT. Omentin is a recently identified adipocytokine, and we previously demonstrated that omentin played anti-inflammatory roles in vascular endothelial and smooth muscle cells. We also demonstrated that omentin induced vasodilation in rat isolated blood vessels. However, effects of omentin on blood pressure (BP) Adipocytes can secrete a variety of cytokines, termed adipocytokine. Obesity with an accumulation of visceral fat is one of the main risk factors for cardiovascular diseases, including hypertension. Adipocytes enlarged by obesity may increase or decrease the production and secretion of adipocytokine. Adipocytokine is thought to regulate obesity-related hypertension by directly acting on vascular system [13,14].Omentin is a recently identified adipocytokine consisting of 313 amino acids [9]. Secretion and plasma concentration of omentin decrease in the obese patients, but increase after a weight loss [2]. We previously demonstrated that omentin was anti-inflammatory in cultured vascular endothelial and smooth muscle cells [5,16]. In addition, we demonstrated that omentin induced vasodilation in rat isolated blood vessels via stimulating endothelial nitric oxide (NO) production [15]. While it is presumed that omentin could regulate blood pressure (BP) in vivo, effects of omentin on BP remain to be determined. Here, we for the first time provided the evidence that omentin can regulate BP in rats. MATERIALS AND METHODS Materials:Reagent sources were as follows: recombinant omentin (BioVendor, Candler, NC, U.S.A.); noradrenaline (NA) and angiotensin II (Ang II) (Sigma-Aldrich, St. Louis, MO, U.S.A.); dimorpholamine (Eisai Co., Ltd., Tokyo, Japan); N G -nitro-l-arginine methyl ester (L-NAME) (Dojindo, Kumamoto, Japan).Physical parameters of rats: Physical parameters of normal Wistar rats (Clea Japan Inc., Tokyo, Japan) or L-NAME-treated Wistar rats (6-10-week-old) were measured. Body weight, heart rate (HR), systolic blood pressure (BP) (SBP), mean BP (MBP) and diastolic BP (DBP) represent the average value (Table 1). Noninvasive BP in conscious rats was measured using a tail-cuff method after heating the rats (38°C) (Softron, Tokyo, Japan) [6,11,12]. L-NAME was dissolved in drinking water and given to rats (80 mg/kg, 1 day).Direct BP measurement: BP and HR of male Wistar rats (130-350 g, 6-10-week-old) were measured under urethane (1.5 g/kg, i.p.) anesthesia as described previously [7,17]. Briefly, the catheter filled with a heparin-saline solution was inserted into carotid artery with a small incision. Catheter was connected to MLT0670 BP transducer (ADInstruments, Colorado Springs, CO, U.S.A.). SBP, MBP and DBP were measured and recorded using ML117 BP Amp (ADInstruments), ML825 PowerLab 2/25 (ADInstruments) system and Chart5 software (ADInstruments). HR was calculated by a cyclic measurement of BP recording. After omentin (0.06-1.8 µg/kg) or saline was intravenously applied for 5 min through the catheter inserted into saphenous vein, NA (0.02-2 µg/kg), Ang II (0.01-10 µg/kg) or dimorpholamine (3 mg/...

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Section: Discussionsupporting

confidence: 74%

“…Body weight, heart rate (HR), systolic blood pressure (BP) (SBP), mean BP (MBP) and diastolic BP (DBP) represent the average value (Table 1). Noninvasive BP in conscious rats was measured using a tail-cuff method after heating the rats (38°C) (Softron, Tokyo, Japan) [6,11,12]. L-NAME was dissolved in drinking water and given to rats (80 mg/kg, 1 day).…”

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confidence: 99%

A Novel Adipocytokine, Omentin, Inhibits Agonists-Induced Increases of Blood Pressure in Rats

Kazama

Okada

Hara

et al. 2013

The Journal of Veterinary Medical Science

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“…[36][37][38][39] To test our hypothesis, we performed vascular functional studies as well as experiments to identify the molecular mechanisms involved. Animals and Experimental Design Male SHR and control WKY were obtained at the age of 4 weeks (Hoshino Laboratory Animals, Inc., Ibaraki, Japan).…”

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confidence: 99%

Relaxation Induced by Atrial Natriuretic Peptide Is Impaired in Carotid but Not Renal Arteries from Spontaneously Hypertensive Rats Due to Reduced BK<sub>Ca</sub> Channel Activity

Matsumoto

Watanabe

Yamada

et al. 2015

Biological & Pharmaceutical Bulletin

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Atrial natriuretic peptide (ANP) plays an important role in vascular functions such as blood pressure regulation and relaxant activity. Individual vascular beds exhibit differences in vascular reactivity to various ligands, however, the difference in responsiveness to ANP between carotid and renal arteries and the molecular mechanisms of its vasorelaxant activity in a pathophysiological state, including hypertension, remain unclear. We therefore investigated this issue by exposing carotid and renal artery rings obtained from spontaneously hypertensive rats (SHR) to ANP. In the SHR artery (vs. control WKY artery), the ANP-induced relaxations were reduced in carotid artery but not renal artery. Acetylcholine-induced relaxations were reduced in both arteries in SHR (vs. WKY). Sodium nitroprusside-induced relaxation was similar in both arteries between the groups. In carotid arteries, the ANP-induced relaxation was not affected by endothelial denudation or by treatment with inhibitors of nitric oxide synthase, cyclooxygenase, the voltage-dependent potassium channel, or ATP-sensitive potassium channel in arteries from both SHR and WKY. In the carotid artery from WKY but not SHR, the ANP-induced relaxation was significantly reduced by inhibition of the large-conductance calcium-activated potassium channel (BK Ca ). The BK Ca activator-induced relaxation was reduced in the SHR artery (vs. WKY). These results suggest that ANP-induced relaxation is impaired in the carotid artery from SHR and this impairment may be at least in part due to the reduction of BK Ca activity rather than endothelial components.Key words atrial natriuretic peptide (ANP); carotid artery; potassium channel; relaxation; spontaneously hypertensive rat (SHR) Hypertension contributes markedly to global cardiovascular morbidity and mortality.1-3) Vascular dysfunction is a hallmark of hypertension and frequently leads to the development of atherosclerosis, stroke, and peripheral arterial disease.1,4) In vascular dysfunction, abnormalities of vascular smooth muscle cells and endothelial cells are key factors in the development of hypertension-associated vascular complications. 5-7)It has been shown that endogenous vasoactive peptides such as angiotensin II, endothelin-1, urotensin II, and natriuretic peptides play an important role in the regulation of vascular tone in (patho) physiological conditions. 8-11) Several reports suggested that the signalings of vasoactive peptides, including their production, metabolism, and affected vascular functions, are altered in arteries from hypertensive patients and animal models.6,10,12) Therefore, the manipulation of vasoactive peptide signaling is one of the most important strategies against the development of vascular dysfunction in hypertension.Atrial natriuretic peptide (ANP) has received particular attention since its effects on the cardiac function and blood pressure regulation have been reported through various mechanisms, including diuretic, natriuretic, and vasorelaxation. [13][14][15][16][17][18][19][20][2...

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“…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 disturbance of this balance can contribute to changes in blood pressure.…”

Section: 18)mentioning

confidence: 99%

“…22,25,[32][33][34] Functional Studies Vascular isometric force was essentially recorded as described in our previous studies. 13,17,22,25,26,28,[32][33][34] Concentration-response curves to ATP (10 for 20 min prior to PE application. To investigate the effect of endothelium on relaxations, we analyzed concentrationresponse curves in the presence/absence of endothelium of superior mesenteric arteries from Wistar rat at 17 weeks of age.…”

Section: 18)mentioning

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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Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats

Cited by 32 publications

References 33 publications

A Novel Adipocytokine, Omentin, Inhibits Agonists-Induced Increases of Blood Pressure in Rats

A Novel Adipocytokine, Omentin, Inhibits Agonists-Induced Increases of Blood Pressure in Rats

Relaxation Induced by Atrial Natriuretic Peptide Is Impaired in Carotid but Not Renal Arteries from Spontaneously Hypertensive Rats Due to Reduced BK<sub>Ca</sub> Channel Activity

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

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