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