Pharmacological evidence of a role for platelet activating factor as a modulator of vasomotor tone and blood pressure

Lopes-Martins, Rodrigo Álvaro Brandão; Catelli, Marcelo Flores; Araujo, Claudia V. de; Estato, Vanessa; Cordeiro, Renato S.B.; Tibiriçá, Eduardo

doi:10.1016/0014-2999(96)00310-x

Cited by 9 publications

(8 citation statements)

References 31 publications

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“…The pulmonary circulation is modulated by a variety of endogenous agents such as nitric oxide, eicosanoids, and PAF (4,19,24,28,34). In the fetus, pulmonary vascular resistance is high due to a greater production of mediators of pulmonary vasoconstriction (16,21).…”

Section: Discussionmentioning

confidence: 99%

Platelet-activating factor receptors in lamb lungs are downregulated immediately after birth

Ibe

Sander

Raj

2000

American Journal of Physiology-Heart and Circulatory Physiology

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Platelet-activating factor (PAF) is a phospholipid with diverse biological functions mediated by a G protein-coupled receptor. We determined PAF receptor binding in lung membranes of four groups of perinatal lambs. Membrane protein (100 microg/ml) was incubated for 60 min at 30 degrees C with 0.5-24 nM of acetyl-[(3)H]PAF in 30 mM Tris buffer, pH 7.2, containing 0.25% BSA, 10 mM MgCl(2), and 125 mM choline chloride. PAF bound to membrane was isolated and quantified by scintillation spectrometry, followed with Scatchard analysis for receptor density (B(max)). The B(max) (means +/- SE, fmol/mg protein) were 445.8 +/- 12.3, 244.2 +/- 3.3, 250.6 +/- 3.6, and 419. 9 +/- 8.6 for the fetal, 90-min-old, <1-day-old, and 6- to 12-day-old lambs, respectively. The B(max) for the 90-min-old and <1-day-old lambs were not different but were significantly lower than those of either the term fetal or 6- to 12-day-old lambs. These data show a significant decrease in PAF binding to its receptor and in PAF B(max) in lung membranes of immediate newborn lambs. The dissociation constants (K(D), nM) were 7.7 +/- 0.52, 11.5 +/- 0.34, 6.9 +/- 0.48, and 5.0 +/- 0.53 for fetal, 90-min-old, <1-day-old, and 6- to 12-day-old newborn lamb lungs, respectively. The K(D) of the 90-min-old lamb was the highest of all. PAF receptor gene measured by RT-PCR showed a significant downregulation of PAF receptor gene mRNA in lungs of lambs <1 day old, suggesting a transcriptional regulation of PAF receptor gene expression in the immediate newborn period. We speculate that decreased PAF receptor binding immediately after birth will facilitate the fall in pulmonary vascular resistance in the immediate newborn period.

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Section: Discussionmentioning

confidence: 99%

Platelet-activating factor receptors in lamb lungs are downregulated immediately after birth

Ibe

Sander

Raj

2000

American Journal of Physiology-Heart and Circulatory Physiology

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“…In previous studies, we have already provided strong evidence that PAF has a physiological role in the regulation of the cardiovascular system, specifically in modulating systemic vascular resistance in the anaesthetised rabbit (Lopes-Martins et al 1996, 1997. Thus, in the present study we used similar pharmacological approaches in order to blunt the potential effects of endogenously released PAF on renal vascular reactivity: blockade of PAF cellular effects using specific PAF receptor antagonists and inhibition of PAF biosynthesis with mepacrine, which is a phospholipase A 2 (PLA 2 ) inhibitor.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, using the experimental model of the anaesthetised rabbit, we provided pharmacological evidence that PAF has a physiological role in the regulation of the cardiovascular function, specifically in the modulation of vascular resistance and, hence, of arterial pressure and blood flow (Lopes-Martins et al 1996, 1997. These results suggest that PAF could be released following acute increases in blood pressure, with this mediator then acting via a negative feedback mechanism which downregulates vascular smooth muscle tone (Lopes-Martins et al 1996).…”

Section: Introductionmentioning

confidence: 97%

“…These results suggest that PAF could be released following acute increases in blood pressure, with this mediator then acting via a negative feedback mechanism which downregulates vascular smooth muscle tone (Lopes-Martins et al 1996). This mechanism could constitute an additional paracrine/ autocrine system of modulation of the smooth muscle cell contractility to the ones exerted by well-known vasoactive substances of endothelial origin such as nitric oxide (NO) and prostacyclin (PGI 2 ; for review see Persson 1996).…”

Section: Introductionmentioning

confidence: 99%

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Involvement of platelet-activating factor in the modulation of vascular tone in the isolated perfused rabbit kidney

Cailleaux¹,

Lopes-Martins²,

Aimbire³

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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The hypothesis that platelet-activating factor (PAF) plays a role in the modulation of the vasomotor tone and blood pressure was put forward by our group in previous in vivo studies in anaesthetised rabbits. The present study was undertaken to investigate the putative role of this lipid mediator in the vascular reactivity of the renal circulation, using the experimental model of the isolated perfused rabbit kidney. Dose-response curves to noradrenaline-induced vasoconstriction were performed before and after continuous infusions of two different PAF-receptor antagonists (WEB 2086 and yangambin) and of the phospholipase A2 inhibitor mepacrine. The increases in renal perfusion pressure elicited by noradrenaline were potentiated by all the above-mentioned treatments in a dose-dependent manner. Moreover, prostaglandin F2alpha-induced vasoconstriction was also potentiated by the administration of the PAF receptor antagonists and mepacrine. Furthermore, the administration of PAF into the renal circulation induced dose-related and long-lasting vasodilator responses, which were blocked by the PAF receptor antagonists. Nevertheless, PAF-induced renal vasodilation was also abolished by a pretreatment with mepacrine or with the cyclooxygenase inhibitor indomethacin, suggesting that it enhances the secondary formation of vasodilator arachidonic acid metabolites. The data indicate that PAF is involved in the modulation of the vasomotor tone in the renal circulation, through the release of cyclooxygenase products, constituting an additional mechanism of modulation of smooth muscle cell contractility to the ones exerted by well-known vasoactive substances of endothelial origin such as nitric oxide.

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“…As PAF is a phospholipidic mediator synthesized by endothelial and smooth muscle cells, its hypotensive effect may be attributed to the dilation of resistance vessels, suggesting its involvement in modulating endothelial dysfunction and vascular smooth muscle tone [ 7 ]. Furthermore, Lopes-Martins et al found that intravenous administration of the PAF receptor antagonist WEB 2086 significantly potentiated the increased systemic vascular resistance induced by noradrenaline or by central activation of the sympathetic nervous system with glutamate, demonstrating that PAF is involved in the modulation of vasomotor tone and, hence, arterial blood pressure by a negative feedback mechanism triggered by important increases in vascular tone [ 9 ]. In addition, fatty acids of the PAF family containing C16 (PAFC16) or C18 (PAFC18) carbon chains promoted renal vasodilation with a decrease in renal vascular resistance and systemic hypotension [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the involvement of platelet-activating factor in the control of hypertension by aerobic training. A randomized controlled trial

Prado,

Castro,

Carvalho

et al. 2024

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Although studies have demonstrated the effectiveness of exercise in controlling systemic arterial hypertension (SAH), the mechanisms involved in this effect are still poorly understood. Thus, this study investigated the impact of aerobic training on the relationship between platelet-activating factor (PAF) circulating levels and blood pressure in hypertensives. Seventy-seven hypertensive subjects were enrolled in this randomized controlled trial (age 66.51 ± 7.53 years, body mass 76.17 ± 14.19 kg). Participants were randomized to two groups: the intervention group (IG, n = 36), composed of hypertensive individuals submitted to an aerobic training protocol, and the control group (CG, n = 41), composed of non-exercised hypertensives. Body mass index, arterial blood pressure, quality of life, respiratory muscle strength, and functional capacity were assessed before and after 12 weeks. PAF and plasma cytokine levels were also evaluated respectively by liquid chromatography coupled with mass spectrometry and enzyme-linked immunosorbent assay. Aerobic training promoted a significant reduction in blood pressure while functional capacity, expiratory muscle strength, and quality of life, PAFC16:0 and PAFC18:1 plasma levels were increased in comparison to the CG (p < 0.05). In addition, multiple correlation analysis indicated a positive correlation [F (3.19) = 6.322; p = 0.001; R 2 adjusted = 0.499] between PAFC16:0 levels and expiratory muscle strength after aerobic training. Taken together, our findings indicate that PAF may be involved in the indirect mechanisms that control SAH, being mainly associated with increased respiratory muscle strength in hypertensive subjects undergoing aerobic training.

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Pharmacological evidence of a role for platelet activating factor as a modulator of vasomotor tone and blood pressure

Cited by 9 publications

References 31 publications

Platelet-activating factor receptors in lamb lungs are downregulated immediately after birth

Platelet-activating factor receptors in lamb lungs are downregulated immediately after birth

Involvement of platelet-activating factor in the modulation of vascular tone in the isolated perfused rabbit kidney

Investigation of the involvement of platelet-activating factor in the control of hypertension by aerobic training. A randomized controlled trial

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