Platelet eicosanoids and the effect of captopril in blood pressure regulation

Mezei, Zsófia; Kis, Béla; Gecse, A; Telegdy, Gyula; Ábrahám, György; Sonkodi, S.

doi:10.1016/s0014-2999(97)01402-7

Cited by 18 publications

(15 citation statements)

References 31 publications

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“…51 12-HHTrE is a lipoxygenase metabolite and nonenzymatic degradation product of prostanoids thromboxane A2 and prostaglandin H2 that has vasoconstrictive effects. 52,53 Given the findings from our study and from previous experimental trials, these results provide a strong biological basis on how eicosanoids affect human BP regulation through several different mechanisms.…”

Section: Discussionsupporting

confidence: 64%

Eicosanoid Inflammatory Mediators Are Robustly Associated with Blood Pressure in the General Population

Palmu

Watrous²,

Mercader³

et al. 2020

Preprint

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Epidemiological and animal studies have associated systemic inflammation with blood pressure (BP). However, the mechanistic factors linking inflammation and BP remain unknown. Fatty acid derived eicosanoids serve as mediators of inflammation and have been suggested to also regulate renal vascular tone, peripheral resistance, renin-angiotensin system, and endothelial function. We therefore hypothesize that specific pro- and anti-inflammatory eicosanoids are linked with BP. We studied a population sample of 8099 FINRISK 2002 participants randomly drawn from the Finnish population register (53% women, mean age 48±13 years) and, for external validation, a sample of 2859 Framingham Heart Study (FHS) Offspring study participants (55% women, mean age 66±9 years). Using non-targeted liquid chromatography-mass spectrometry, we profiled 545 distinct high-quality eicosanoids and related oxylipin mediators in plasma. Adjusting for conventional hypertension risk factors, we observed 187 (34%) metabolites that were significantly associated with systolic BP (P < Bonferroni-corrected threshold of 0.05/545). We used forward selection linear regression modeling in FINRISK to define a general formula for individual eicosanoid risk score. Individuals of the top risk score quartile in FINRISK had a 9.0 mmHg (95% CI 8.0-10.1) higher systolic BP compared with individuals in the lowest quartile in fully adjusted models. Observed metabolite associations were consistent across FINRISK and FHS. In conclusion, plasma eicosanoids demonstrate strong associations with BP in the general population. As eicosanoid compounds affect numerous physiological processes that are central to BP regulation, they may offer new insights regarding pathogenesis of hypertension, as well as serve as potential targets for therapeutic intervention.

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Section: Discussionsupporting

confidence: 64%

Eicosanoid Inflammatory Mediators Are Robustly Associated with Blood Pressure in the General Population

Palmu

Watrous²,

Mercader³

et al. 2020

Preprint

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“…Ten minutes later, the enzyme reaction was stopped by bringing the pH of the incubation mixture to 3 with formic acid. The ''C-eicosanoids were separated by means of overpressure thin-layer chromatography and determined quantitatively by liquid scintillation, as described previously (16).…”

Section: Study Of the Platelet Aa Cascadementioning

confidence: 99%

Valproate Treatment and Platelet Function: The Role of Arachidonate Metabolites

et al. 1999

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Summary:Purpose: Valproate (VPA) is an extensively used drug in the therapy of epilepsies. One of the most frequently reported side effects of VPA is hemorrhagic diathesis. Some authors emphasized the decreased platelet count as the basis of VPA-induced hemorrhagic diathesis, but some reports suggested that a significant proportion of patients with normal platelet count may still have an altered platelet function. The mechanism of the VPA-induced platelet dysfunction has not yet been elucidated. A determining element of platelet functions is the arachidonate cascade. Present ex vivo experiments were designed to determine whether a relation exists between the incidence of hemostasis caused by VPA and the effect of this drug on the arachidonate cascade of platelets.Methods: Platelets were isolated from patients receiving long-term VPA treatment (serum level, 36.04 f 16.12 pg/ml; n = 10) or carbamazepine (CBZ) treatment (serum level, 5.24 + 2.67 yg/ml; n = 10) and were labeled with ['4C]arachidonic acid. (CBZ-treated patients were chosen as a control group, because CBZ causes blood dyscrasias similar to those elicited by VPA, but there has been no report that CBZ induces a platelet dysfunction.) The ''C-eicosanoids were separated by means of overpressure thin-layer chromatography and determined quantitatively by liquid scintillation.Results: Even when the mean plasma concentration of the drug was low, VPA treatment reduced the activity of the arachidonate cascade in platelets. VPA effectively inhibited the cyclooxygenase pathway and the synthesis of the strong platelet aggregator thromboxane A,.Conclusions: Inhibition of the platelet arachidonate cascade may contribute to the platelet-function alterations caused by VPA.

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“…Platelets were isolated from blood drawn from the abdominal aorta of male Wistar rats (body weight: 185 ±15 g), under light ether anesthesia according to our method described earlier [8]. After the last centrifugation, the platelets were resuspended (10 8 or 10 9 platelets/ml) in serum–free tissue culture Medium 199.…”

Section: Methodsmentioning

confidence: 99%

“…The enzyme reaction was started by the application of tracer substrate, 1–[ 14 C]–arachidonic acid (3.7 kBq, 0.172 pmol), to the incubation mixture. Ten minutes later, the synthesized metabolites were extracted and quantitatively determined by our earlier described method [8]. Animal experiments were performed with the permission of the Ethical Committee for the Protection of Animals in Research (Albert Szent–Györgyi Medical University, Hungary).…”

Section: Methodsmentioning

confidence: 99%

Effects of Inflammatory Neuropeptides on the Arachidonate Cascade of Platelets

Gecse

Kis²,

Mezei³

et al. 1999

Int Arch Allergy Immunol

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Background: During neurogenic inflammation, neuro–peptides (substance P, SP, calcitonin gene–related peptide, CGRP, and neurokinin A) are released from nerve endings, and these peptides initiate inflammatory reactions in the microcirculation. Platelets are one of the most important elements of the microcirculation. Methods: Our in vitro experiments were carried out to determine the effects of inflammatory neuropeptides (SP, and CGRP) on the arachidonate cascade of isolated rat platelets. Cells were labeled with 1–¹⁴C–arachidonic acid, then the eicosanoids were separated with overpressure thin–layer chromatography or high–performance liquid chromatography and were quantitatively determined with a liquid scintillation analyzer. Results: SP (10^–9 and 10^–8 mol/l) significantly increased the activity of the arachidonate cascade. The lipoxygenase pathway was significantly stimulated by SP (10^–11, 10^–9 and 10^–8 mol/l), while the cyclooxygenase system was inhibited by 10^–12 mol/l, and stimulated by 10^–9 mol/l SP. The dose–response curve of TxA₂ to SP exhibited a similar pattern to that detected for the cyclooxygenase pathway. Among the vasodilator cyclooxygenase metabolites, only the synthesis of PGE₂ was significantly elevated by SP (10^–9 mol/l ). CGRP either in low (10^–12–10^–11 mol/l) or in high concentrations (10^–6 mol/l) activated the cyclooxygenase pathway, while it had no effect on the lipoxygenase pathway. CGRP (8–37), a specific CGRP1 receptor antagonist, inhibited the effects of CGRP. Conclusions: Our data suggest that the arachidonate metabolites of platelets may play a role in the process of neurogenic inflammation.

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Platelet eicosanoids and the effect of captopril in blood pressure regulation

Cited by 18 publications

References 31 publications

Eicosanoid Inflammatory Mediators Are Robustly Associated with Blood Pressure in the General Population

Eicosanoid Inflammatory Mediators Are Robustly Associated with Blood Pressure in the General Population

Valproate Treatment and Platelet Function: The Role of Arachidonate Metabolites

Effects of Inflammatory Neuropeptides on the Arachidonate Cascade of Platelets

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