Simultaneous Measurements of Cytosolic Free Calcium Level and Prostaglandin Synthesis Reveal a Correlation between Them in Perfused Monolayer of Cultured Rat Vascular Smooth Muscle Cells: Effects of Bradykinin and Angiotensin II.

Takeuchi, Kazuhisa; Abe, Keishi; Maeyama, Kazutaka; Sato, Makito; Yasujima, Minoru; Watanabe, Takehiko; Yoshinaga, Kaoru

doi:10.1620/tjem.165.183

Cited by 5 publications

(6 citation statements)

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“…The most probable alternative mechanism is Ca 2ϩ -dependent activation of phospholipase A 2 , which is well described in VSMCs. 21 cis-Unsaturated NEFAs have multiple effects on membrane transport, including effects on Ca 2ϩ flux. 28 Consequently, the effects of NEFAs on intracellular Ca 2ϩ levels in VSMCs were examined.…”

Section: Discussionmentioning

confidence: 99%

“…This relationship is steep and saturable within the physiological range of intracellular Ca 2ϩ . 21 Thus, the Ca 2ϩ response to oleic acid may be sufficient to elicit full phospholipase A 2 activation. Although additional studies are required to further delineate the signaling mechanism, these data suggest that oleic and linoleic acids can evoke a Ca 2ϩ -dependent activation of phospholipase A 2 in VSMCs with hydrolysis of arachidonic acid from complex lipids which leads to the generation of COX products.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, additional experiments were performed to determine if oleic and linoleic acids raise intracellular Ca 2ϩ in VSMCs, which could activate phospholipase A 2 and lead to the generation of COX products. 20,21 As illustrated in Figure 3, the addition of oleic or linoleic acids to VSMCs at 100 mol/L concentrations was associated with significant increases in intracellular Ca 2ϩ detected by the FLIPR. In contrast, equimolar concentrations of stearic and elaidic acids had no effect on calcium flux.…”

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confidence: 98%

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Lipids Stimulate the Production of 6-keto-prostaglandin F _1α in Human Dorsal Hand Veins

et al. 2001

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Abstract-Obese hypertensives have increased nonesterified fatty acids (NEFAs) and ␣-adrenergic vascular reactivity.Raising NEFAs locally with intralipid and heparin augments dorsal hand venoconstrictor responses to phenylephrine, an ␣ 1 -adrenoceptor agonist. The enhanced venoconstrictor responses were reversed by indomethacin. The findings suggest that raising NEFAs leads to the generation of cyclooxygenase (COX) product(s) that enhance vascular reactivity. To test this notion, 6-keto-PGF 1␣ and TxB 2 , the stable metabolites of prostaglandin H 2 (PGH 2 ); prostacyclin (PGI 2 ); and thromboxane (TxA 2 ), were measured Ϸ1.5 to 2 cm downstream of a dorsal hand vein infusion of intralipid and heparin (nϭ10) or saline and heparin (nϭ5) for 2 hours each. During the third hour, intralipid and heparin (experimental) and saline and heparin (control) were continued, and either saline (control) or indomethacin (intervention) were infused. Intralipid and heparin raised local 6-keto PGF 1␣ concentrations by 350% to 500% (PϽ0.005), but saline and heparin did not (PϭNS). TxB 2 levels did not change significantly with any infusion. Infusion of indomethacin during the third hour of intralipid and heparin lowered plasma 6-keto-PGF 1␣ (PϽ0.05), whereas infusion of saline with intralipid and heparin did not (PϭNS). Oleic and linoleic acids at 100 mol/L, increased 6-keto-PGF 1␣ in vascular smooth muscle cells (VSMCs) through a protein kinase C and extracellular, signal-regulated kinase independent pathway. However, oleic and linoleic acids increased intracellular Ca 2ϩ in VSMCs. The data indicate that NEFAs induce the production of COX products, perhaps via Ca 2ϩ -dependent activation of phospholipase A 2 . The COX product(s) may contribute to increased vascular ␣-adrenergic reactivity among insulin-resistant individuals when NEFAs are elevated. Key Words: fatty acids Ⅲ prostaglandins Ⅲ muscle, vascular, smooth Ⅲ cyclooxygenase O bese hypertensives have increased vascular ␣-adrenergic reactivity and tone as well as elevated non-esterified fatty acids (NEFAs) which are resistant to suppression by insulin. [1][2][3] In lean normotensives, raising NEFAs with intralipid and heparin enhances local and systemic sensitivity to phenylephrine, an ␣ 1 -adrenoceptor agonist. 4 -6 In the hand vein studies, raising NEFAs locally enhanced ␣ 1 -adrenergic vasoconstriction and endotheliumdependent dilation via an indomethacin-sensitive mechanism, which implicates cyclooxygenase (COX) product(s) in the altered vascular reactivity. 6 cis-Unsaturated NEFAs, eg, oleic acid, activate a sequential signaling pathway that includes protein kinase C (PKC), reactive oxygen species (ROS), and extracellular signal-regulated kinases (ERKs). 7,8 ERKs can induce a Ca 2ϩ -independent activation of phospholipase A 2 with hydrolysis of arachidonic acid from complex lipids, 9 leading to the subsequent generation of eicosanoid products. Alternatively, linoleic but not oleic acid can be elongated and desaturated to arachidonic acid. 10 Arachidonic acid is converted b...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 98%

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Lipids Stimulate the Production of 6-keto-prostaglandin F _1α in Human Dorsal Hand Veins

et al. 2001

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“…On the other hand, ang II has been shown to stimulate vasodilator PG synthesis in vascular smooth muscle (Alexander and Gimbrone 1976; Hassid and Williams 1983; Takeuchi et al 1985) via PLA2/cyclooxygenase. We have also shown that ang II simultaneously stimulates an increase in cytosolic free calcium and PG (prostacyclin) synthesis, indicating that ang II receptor can be linked to both PLC and PLA2 pathways at the same time (Takeuchi et al 1991b). Moreover, ang II is also known to induce a biphasic vascular response of initial contraction (due to an increase in cytosolic calcium (Ca2+)) and subsequent dilatation (due to production of vasodilator PG) (Blumberg et al 1977).…”

Section: Discussionmentioning

confidence: 82%

A Case of Secondary Aldosteronism Similar to Bartter's Syndrome with No Abnormality in Renal Chloride Reabsorption.

Takeuchi

Imai

Omata

et al. 1993

Tohoku J. Exp. Med.

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We had a 20-year-old male patient of secondary aldosteronism similar to Bartter's syndrome, which had proved to be evident after the remission of nephrotic syndrome. In the patient, hypokalemic alkalosis and hyperreninemic hyperaldosteronemia were observed, although the blood pressure was normal. Hyperplasia of juxtaglomerular cells was observed and no abnormalities indicating either glomerulonephritis or renal artery stenosis were found; the pressor response to intravenously infused angiotensin (ang) II was markedly decreased ; urinary prostaglandin (PG) E2, kallikrein and kinin excretion were elevated. The inhibition of PG synthesis with indomethacin decreased renal PG production and partially corrected both hypokalemia and pressor responsiveness to ang II. Thus, this case is considered to be a case of Bartter's syndrome. Contrary to the previously reported observations, the effective fractional chloride reabsorption rate in the renal distal tubules was normal (>80%) and not changed by PG inhibition. Plasma atrial natriuretic peptide level was normal. An interaction between renin-angiotensin and PG systems appears to play a prior role in this case. To explain the pathophysiology, we have hypothesized an abnormal function of ang II receptor signal transduction which excessively stimulates PLA2, resulting in overproduction of PG synthesis in tissues.prostaglandin ; nephrotic syndrome ; angiotensin II receptor ; kallikrein-kinin system ; atrial natriuretic peptide Secondary aldosteronism refers to an appropriately increased production of adrenal aldosterone in response to activation of the renin-angiotensin (R-A) system, while primary aldosteronism is due to an adrenal adenoma autonomously secreting mineralocorticoids.Secondary aldosteronism, therefore, occurs in such a pathophysiologic condition as a decrease in effective plasma volume (i.e.,

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“…Watanabe et al [40] showed that the correlation between the agonist-stimulated rises in [Ca 2+]i and production of PGIz in three vascular endothelial cell lines varied with the agonist and the cell line. Takeuchi et al [38] demonstrated the correlation between bradykinin-stimulated intracellular calcium level and prostaglandin synthesis in rat vascular smooth muscle cells, and many investigators have demonstrated that airway smooth muscle con- Bradykinin (M) Fig. 4.…”

Section: Discussionmentioning

confidence: 98%

Arachidonic acid metabolites and glucocorticoid regulatory mechanism in cultured porcine tracheal smooth muscle cells

Tanaka

Watanabe

Tamaru

et al. 1995

Lung

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To elucidate the signal transduction system in the production of prostaglandin E2 (PGE2) by porcine tracheal smooth muscle cells in culture (PTSMC), we examined the pattern of arachidonic acid metabolites released from PTSMC and the relationship between bradykinin-stimulated rises in intracellular calcium concentration ([Ca2+]i) and PGE2 production by PTSMC. We next examined the effect of dexamethasone on these parameters. Bradykinin induced a dose-dependent increase in both the rise in [Ca2+]i and PGE2 production by PTSMC. The increase in [Ca2+]i paralleled an increase in PGE2 production. High-performance liquid chromatography (HPLC) revealed that dexamethasone-treated PTSMC were suppressed to release arachidonic acid metabolites such as PGE2 and prostaglandin F2 alpha (PGF2 alpha). Incubation of PTSMC with 10(-6)M dexamethasone for 24 h significantly suppressed both the rise in [Ca2+]i and PGE2 production by PTSMC in response to bradykinin, and also significantly suppressed bradykinin-stimulated release of radioactivity from PTSMC prelabeled with 3H-labeled arachidonic acid (3H-AA). When PTSMC pretreated with dexamethasone were incubated with 170 nM prostaglandin H2 (PGH2) or 20 microM arachidonic acid; PTSMC synthesized less PGE2 than control PTSMC. Results suggest that bradykinin stimulates PTSMC to produce PGE2 via the signal transduction system including Ca2+, and dexamethasone appeared to suppress PGE2 production by reducing the activity of cytosolic phospholipase A2 (cPLA2) and PGE2 synthase. However, we failed to demonstrate the suppression of the activity of cyclooxygenase in PTSMC by dexamethasone. Since the elevation of [Ca2+]i is necessary for the contraction of airway smooth muscles, dexamethasone seems to reduce the contraction of airway smooth muscles by suppressing the rise in [Ca2+]i and the release of arachidonic acid metabolites. Reduced production of arachidonic acid metabolites may also contribute to improvement in the bronchial inflammation.

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Simultaneous Measurements of Cytosolic Free Calcium Level and Prostaglandin Synthesis Reveal a Correlation between Them in Perfused Monolayer of Cultured Rat Vascular Smooth Muscle Cells: Effects of Bradykinin and Angiotensin II.

Cited by 5 publications

References 22 publications

Lipids Stimulate the Production of 6-keto-prostaglandin F _1α in Human Dorsal Hand Veins

Lipids Stimulate the Production of 6-keto-prostaglandin F _1α in Human Dorsal Hand Veins

A Case of Secondary Aldosteronism Similar to Bartter's Syndrome with No Abnormality in Renal Chloride Reabsorption.

Arachidonic acid metabolites and glucocorticoid regulatory mechanism in cultured porcine tracheal smooth muscle cells

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Simultaneous Measurements of Cytosolic Free Calcium Level and Prostaglandin Synthesis Reveal a Correlation between Them in Perfused Monolayer of Cultured Rat Vascular Smooth Muscle Cells: Effects of Bradykinin and Angiotensin II.

Cited by 5 publications

References 22 publications

Lipids Stimulate the Production of 6-keto-prostaglandin F 1α in Human Dorsal Hand Veins

Lipids Stimulate the Production of 6-keto-prostaglandin F 1α in Human Dorsal Hand Veins

A Case of Secondary Aldosteronism Similar to Bartter's Syndrome with No Abnormality in Renal Chloride Reabsorption.

Arachidonic acid metabolites and glucocorticoid regulatory mechanism in cultured porcine tracheal smooth muscle cells

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Product

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Lipids Stimulate the Production of 6-keto-prostaglandin F _1α in Human Dorsal Hand Veins

Lipids Stimulate the Production of 6-keto-prostaglandin F _1α in Human Dorsal Hand Veins