Abnormal Ca2+ Handling and Increased Mg2+ Permeability in Platelets of Hypertensive Rats.

Oshima, Tetsuya; Nakano, Yukiko; Ozono, Ryoji; Higashi, Yukihito; Sasaki, Shota; Ueda, Atsushi; Oue, Yasuo; Matsuura, Hideo; Kambe, Masayuki

doi:10.1291/hypres.23.651

Cited by 6 publications

(2 citation statements)

References 37 publications

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“…The primary defect in this model seems to occur in the Ca 2 regulatory system in arterial smooth muscle (30). A large Ca 2 influx and a high [Ca 2 ]i have been reported even in the resting state of arteries (9,10,31,32) and platelets (33) from SHR when compared with WKY. The finding that Y-27632 strongly inhibited the K contraction may suggest that this agent inhibits Ca 2 influx via Ltype Ca 2 channels.…”

Section: Discussionmentioning

confidence: 85%

Comparison of Inhibitory Effects of Y-27632, a Rho Kinase Inhibitor, in Strips of Small and Large Mesenteric Arteries from Spontaneously Hypertensive and Normotensive Wistar-Kyoto Rats.

Asano

Nomura

2003

Hypertens Res

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Since Y-27632, a specific inhibitor of Rho kinase, decreases the blood pressure in spontaneously hypertensive rats (SHR), it is suggested that Rho kinase is involved in the pathophysiology of hypertension. However, the effects of Y-27632 on isolated resistance arteries have never been determined. This study aimed to examine the possible role of the Rho/Rho kinase pathway during arterial contraction in isolated resistance arteries from SHR. The profile of arterial relaxant effects of Y-27632 was compared in endothelium-denuded strips of small and large mesenteric arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY). The addition of 10(-6) mol/l norepinephrine (NE) to the strips of small arteries caused an initial peak followed by a tonic contraction in both strains. There was no difference between the two strains in either the initial peak or the tonic contraction. The addition of Y-27632 (0.3-3 micromol/l) to the tonic contraction of these strips caused a concentration-dependent relaxation in both strains. The relaxation was greater in SHR than in WKY. Similar results were observed in strips of large arteries. The relaxant effects of Y-27632 were greater in the large artery than in the small artery. Y-27632 also induced a concentration-dependent relaxation in strips precontracted with 65.9 mmol/l K+ depolarization. In both arteries, this relaxation was greater in SHR. The relaxant effects of Y-27632 were greater in the K+-contracted strips than in the NE-contracted strips. We conclude that Y-27632 shows the greater relaxant effects on the SHR arteries, and the effects are more evident in the large artery and in the K+-contracted strips.

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Section: Discussionmentioning

confidence: 85%

Comparison of Inhibitory Effects of Y-27632, a Rho Kinase Inhibitor, in Strips of Small and Large Mesenteric Arteries from Spontaneously Hypertensive and Normotensive Wistar-Kyoto Rats.

Asano

Nomura

2003

Hypertens Res

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“…Increased cytosolic calcium concentration ([Ca 2 ]i) and abnormal Ca 2 handling have been widely demonstrated in a variety of cell types from patients with essential hyperten-and thrombin-induced aggregation response are increased in platelets from spontaneously hypertensive rats (SHR) (6)(7)(8)(9)(10)(11)(12). However, there is a possibility that the exposure of circulating blood cells to the mechanical shear forces in the circulatory system could alter cellular Ca 2 metabolism or cell function.…”

Section: Introductionmentioning

confidence: 99%

Effect of Amlodipine and Cilazapril Treatment on Platelet Ca2+ Handling in Spontaneously Hypertensive Rats

et al. 2003

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Abnormal Ca2+ handling and enhanced aggregation response have been reported in platelets from spontaneously hypertensive rats (SHR) and patients with essential hypertension, and thought to be involved in the progression of target organ damage of hypertension. It is important to examine whether antihypertensive therapy can improve the abnormal platelet response in hypertension. We investigated the effect of antihypertensive treatment such as amlodipine and cilazapril on Ca2+ handling and aggregation response in SHR platelets. Four-week-old male SHR were divided into three groups. Each group was treated with amiodipine (A: 10 mg/kg/day), cilazapril (C: 10 mg/kg/day) or vehicle (V) for 8 weeks by gavage. At 12-week-old, platelet [Ca2+]i was measured with fura-2 in each group of SHR and age-matched Wistar-Kyoto rats (WKY) as normal control. Systolic blood pressure in amlodipine and cilazapril treated groups were similar with WKY and significantly lower than vehicle treated group (A: 124 +/- 9, C: 126 +/- 9, WKY: 122 +/- 10 and V: 180 +/- 9 mmHg, respectively). The basal [Ca2+]i in the three groups of SHR were similar and higher than WKY (A: 47 +/- 1.7, C: 47 +/- 1.2, V: 48 +/- 3.9 and WKY: 40 +/- 4.0 nmol/l, respectively). There were no significant differences in thrombin (0.1 U/ml)-stimulated [Ca2+]i rise in the presence or absence of extracellular Ca2+ among the three groups of SHR and these were higher than WKY. Intracellular Ca2+ discharge capacity, assessed by the ionomycinstimulation was similar in the all groups. Thrombin-induced maximum platelet aggregation responses in the three groups of SHR were similar and higher than WKY. The antihypertensive treatment of Ca2+ antagonist or ACE inhibitor gave no change in intraplatelet Ca2+ metabolism in SHR. These results support the hypothesis that an abnormal Ca2+ handling in SHR platelet is genetically determined and not improved by hypotensive therapy.

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Electrolytes and pH changes in pre-eclamptic rats

Ebose

Campbell

Okorodudu

2007

Clinica Chimica Acta

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Abnormal Ca2+ Handling and Increased Mg2+ Permeability in Platelets of Hypertensive Rats.

Abstract: In order to test the hypothesis that intracellular Na+ accumulation and cellular Mgz+ deficiency may be involved in the abnormalities in Ca2+ handling and reactivity in spontaneously hypertensive rats (SHR) platelets, the metabolism of Na+, Ca2+

Cited by 6 publications

References 37 publications

Comparison of Inhibitory Effects of Y-27632, a Rho Kinase Inhibitor, in Strips of Small and Large Mesenteric Arteries from Spontaneously Hypertensive and Normotensive Wistar-Kyoto Rats.

Comparison of Inhibitory Effects of Y-27632, a Rho Kinase Inhibitor, in Strips of Small and Large Mesenteric Arteries from Spontaneously Hypertensive and Normotensive Wistar-Kyoto Rats.

Effect of Amlodipine and Cilazapril Treatment on Platelet Ca2+ Handling in Spontaneously Hypertensive Rats

Electrolytes and pH changes in pre-eclamptic rats

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