Acute cardiovascular effects of (+)-nantenine, an alkaloid isolated from Platycapnos spicata, in anaesthetised normotensive rats.
This is the first study of the in vivo potential activity of (+)-nantenine (a natural aporphinoid alkaloid) on the rat cardiovascular system. In anaesthetized normotensive rats, acute intravenous ( i. v.) administration of (+)-nantenine (3 - 6 mg/kg) produced a dose-dependent fall in mean arterial pressure (MAP), accompanied by a significant decrease in heart rate (HR). In addition, (+)-nantenine (5 mg/kg i. v.) did not modify the cardiovascular effects induced by angiotensin II (0.2 microg/kg i. v.) and the selective alpha (2)-adrenoceptor agonist B-HT 920 (0.2 mg/kg i. v.) [unlike nifedipine (0.8 mg/kg i. v.) and yohimbine (1 mg/kg i. v.), respectively] but markedly attenuated [like prazosin (0.2 mg/kg i. v.)] the hypertension evoked by phenylephrine (PE, 25 microg/kg, i. v.), a selective alpha (1)-adrenergic receptor agonist and, like ketanserin (1 mg/kg i. v.), the second phase (rise in MAP) of the cardiovascular response caused by 5-hydroxytryptamine (5-HT, 0.3 mg/kg i. v.). On the other hand, pre-treatment of anaesthetised rats with NG-nitro- L-arginine ( L-NOARG, 5 mg/kg i. v.) did not significantly affect the cardiovascular effects of (+)-nantenine. These results indicate that the hypotension and bradycardia elicited by this aporphine alkaloid in anaesthetised normotensive rats seem to be due, at least in part, to a combined alpha (1)-adrenergic and 5-HT (2A) receptor blockade but not to the release of nitric oxide (NO) from vascular endothelium, to an alpha (2)-adrenoceptor antagonism or to a calcium antagonist activity. Abbreviations. BP:blood pressure HR:heart rate 5-HT:5-hydroxytryptamine i. v.:intravenous L-NOARG: NG-nitro- L-arginine MAP:mean arterial pressure NO:nitric oxide PE:phenylephrine
Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, Spain. fforallo@usc.es
Francisco
F
Orallo
D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001060:Aporphines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D028101:Papaveraceae; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D000470:Alkaloids; D000959:Antihypertensive Agents; D001060:Aporphines; D010936:Plant Extracts; C041615:nantenine