C. C. T. Smith

Platelet function in patients with hypercholesterolaemia

Abstract. Platelets and plasma lipoproteins, particularly low density lipoprotein, have important roles in atherogenesis. Evidence from several sources suggests that important interactions occur between these individual components of the atherogeneic process. Here we review work from our own laboratory on platelet function in normal individuals and patients heterozygous for familial hypercholesterolaemia (FH). Data is presented on the role of platelet noradrenaline and also on altered cellular signalling in platelets from FH individuals who have plasma low density lipoprotein concentrations which are approximately double those seen in normal subjects.

Platelet noradrenaline release in patients with familial hypercholesterolaemia.

Abstract. We have examined resting and thrombin (0.3 units ml‐1) induced release of noradrenaline by washed platelets from 15 normal subjects and eight patients with heterozygous familial hypercholesterolaemia.

Platelet in vitro responses to urapidil and prazosin.

Urapidil is an antihypertensive agent with aq-, and weak a2-adrenoceptor blocking activity in the nervous system (Jackisch et al. 1987; van Zwieten et al. 1985). Some animal experiments have suggested a modest ,B-adrenoceptor antagonistic action (Freissmuth et al. 1984; Verberne & Rand 1985), but there is no evidence of this in man (Prichard et al. 1989; Tomlinson et al., in preparation). In addition, agonist activity at serotoninix receptors has been reported (Fozard & Mir 1987; Kolassa et al. 1989). Prazosin, a quinazoline derivative, acts preferentially on al-adrenoceptors (Hornung et al. 1979). a2-Adrenoceptor antagonists are known to inhibit catecholamine-induced platelet aggregation (Mills & Roberts 1967; OBrien 1963). In contrast, a2-adrenoceptor agonists (e.g. clonidine) can enhance platelet aggregation (Grant & Scrutton 1980). Thus, an a2-adrenoceptor antagonist which inhibits platelet aggregation may prove useful in reducing platelet activity in some conditions, particularly in hypertension where the involvement of catecholamines in the pathogenesis of the disease is suspected (Hjemdahl 1988). Although ,B-adrenoceptor antagonists also inhibit platelet aggregation (Kerry et al. 1984), this is believed to result from a platelet membrane stabilising effect of the drugs, rather than an action on ,B-adrenoceptors. In the present study, the action of urapidil and prazosin, an al-adrenoceptor blocker, on human platelet aggregation and catecholamine release in vitro has been examined.

Influence of the alpha-adrenoreceptor naftopidil and doxazosin, on adrenaline-induced serotonin platelets: comparison with the antagonists, collagen and efflux by human effects of nifedipine.

Collagen (5 microg/ml) stimulation of washed platelets increased endogenous serotonin (5-HT) release to the medium from 13.88 1.39 to 188.67 26.37 pmol/108 platelets ( P < 0.001). Adrenaline (16 microM) also increased 5-HT release, from 11.0 1.46 to 110.6 29.9 pmol/108 platelets ( P < 0.02). Naftopidil enhanced collagen-induced 5-HT efflux; significant increases occurred with 2 microM (+71.6%, P < 0.01), 10 microM (+89.1%, P < 0.01) and 40 microM (+69.7%, P < 0.01). With 0.4 muM and 2 microM naftopidil, adrenaline-induced 5-HT release was enhanced, albeit non-significantly, whilst with 10 microM and 40 muM naftopidil release was reduced (40 microM,-58.5%, P < 0.05). Doxazosin increased collagen-induced 5-HT release, significant increases being recorded with 7.5 microM (+81.7%, P < 0.05) and 30 microM (+78.4%, P < 0.05). Adrenaline-induced 5-HT release was also increased by doxazosin, but not significantly. Collagen-stimulated 5-HT release was inhibited by nifedipine (7 microM,-38.8%, P < 0.05; 28 microM, -61.2%, P < 0.001). These data suggest that the-antagonists, naftopidil and doxazosin, and the Ca2+ channel blocker, nifedipine, influence agonist-induced platelet 5-HT release through different mechanisms. Thus naftopidil and doxazosin may possess 5-HT transporter-blocking activity. The observation that naftopidil inhibited, adrenaline-induced 5-HT release may indicate that naftopidil also inhibits adrenaline uptake and exchange with dense granular 5-HT, with consequent inhibition of 5-HT release and platelet aggregation. The data obtained with nifedipine are consistent with 5-HT release being reduced as a result of its inhibitory action on platelet Ca2+ mobilisation.

Collagen-induced Platelet Activation In Vitro Increases Plasma Catecholamine Concentration

Collagen-induced Platelet Activation In Vitro Increases Plasma Catecholamine Concentration C. C. T. Smith, B. N. C. Prichard & D. J. Betteridge To cite this article: C. C. T. Smith, B. N. C. Prichard & D. J. Betteridge (1992) Collagen-induced Platelet Activation In Vitro Increases Plasma Catecholamine Concentration, Platelets, 3:4, 217-218 To link to this article: http://dx.doi.org/10.3109/09537109209013186