Lercanidipine showed a high antihypertensive effect in CRF patients. It has a good tolerability profile and showed an interesting effect on plasmatic lipids. An improvement in renal function, measured through creatine clearance, was detected.
Our present data support the concept that repeated platelet stress during hemodialysis has a deleterious effect on the organization of platelet cytoskeleton, which seems to impair the translocation of signal transduction proteins within platelets compromising the platelet function in uremia.
Recombinant human erythropoietin improves platelet function in uremia through the correction of anemia, but this effect can be seen also before the hematocrit rise. We studied 12 hemodialyzed patients (seven men, five women) who received recombinant human erythropoietin (40 IU kg(-1)i.v., three times weekly) and were evaluated before treatment and after three doses; 24 control subjects were used. Platelet aggregation induced by adenosine 5'-diphosphate (ADP), epinephrine, collagen, arachidonic acid, and ristocetin, and reticulated platelets determined by flow cytometry after staining with thiazole orange were measured. Platelet aggregation induced by all the agonists were impaired in uremic patients (P < 0.01), but ADP and ristocetin-induced aggregations improved after treatment (P < 0.01). Hemodialyzed patients had less reticulated platelets than controls (P < 0.01). Reticulated platelets increased after three doses of treatment (P < 0.01). In conclusion, improvement of platelet function at early stages of recombinant human erythropoietin treatment may be attributed to the increase in young platelets detected as reticulated platelets.
To study the effect of chronic exposure to elevated plasma catecholamines on surface beta 2-adrenoceptor density, we measured these receptors in the lymphocytes of 9 patients with pheochromocytoma as well as in 27 healthy control subjects. Binding experiments were performed on intact lymphocytes using the hydrophilic ligand [3H]-CGP12177. Lymphocyte beta 2-adrenergic response was also measured in three patients. beta 2-adrenoceptor density (p < 0.01), and isoproterenol-stimulated increase in cAMP were reduced in patients with pheochromocytoma. Both parameters normalized (p < 0.05) when patients were reevaluated 4 weeks after tumor removal, coinciding with normalization of plasma epinephrine (r = -0.95, p < 0.01) and to log of plasma norepinephrine (r = -0.58, p < 0.05) in patients. We conclude that chronic catecholamine excess induces a decrease of lymphocyte beta 2-adrenoceptor surface number and response that is reversible upon normalization of plasma catecholamine levels. This regulation is mainly dependent on plasma levels of the hormone epinephrine, but norepinephrine may also play a regulatory role at supraphysiological levels.
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