[Evaluation of acute and chronic effects of ketanserin in the treatment of hypertension and hypothesis on a new mechanism of action].
Ketanserin is a specific antagonist of the 5-HT2 serotoninergic receptors; it is located on the smooth muscle cells of the vessel wall, and its stimulation causes vasoconstriction. The aim of this study is to evaluate the antihypertensive effect of ketanserin in patients with essential and secondary hypertension. Both systolic and diastolic blood pressure significantly decreased, in 18 patients, after chronic treatment with oral therapy (40-80 mg/day), and in 37 patients, after acute administration of sublingual (20 mg) and intravenous (10 mg) ketanserin. Acute administration of ketanserin was less effective than nifedipine (10 mg) in severe hypertension. Ketanserin, compared to placebo, permitted the normalization of blood pressure in 6/10 patients. Cardiovascular effects of ketanserin were studied with the ECOCG method in 8 patients with hypertension: peripheral resistances decreased, but left ventricular function and structure did not change. The effect of ketanserin on Na transmembrane transport systems in erythrocytes was studied both in vivo and in vitro, in order to evaluate the ketanserin action mechanism. The Na/K pump decreased and Na/Li countertransport increased, while different concentrations of serotonin did not change the transmembrane transport systems. In conclusion, ketanserin has a direct effect on transmembrane transport systems, not mediated by the serotonin receptors. This effect, with an antagonist of 5-HT2 serotoninergic and alpha 1 adrenergic receptor action, can cause a hypotensive effect.
Sechi
L A
LA
Istituto di Clinica Medica Generale e Terapia Medica, Università degli Studi di Sassari.
D000328:Adult; D000368:Aged; D001669:Biochemical Phenomena; D001671:Biochemistry; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D007650:Ketanserin / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use; D011188:Potassium / Q000097:blood; D012083:Renin / Q000097:blood; D012964:Sodium / Q000097:blood
D007650:Ketanserin; D012964:Sodium; D012083:Renin; D009543:Nifedipine; D011188:Potassium
Valutazione degli effetti acuti e cronici della ketanserina nel trattamento dell'ipertensione e ipotesi su un nuovo meccanismo di azione.