Acute Cardiovascular Effects of (+)-Nantenine, an Alkaloid Isolated from Platycapnos spicata, in Anaesthetised Normotensive Rats

Abstract

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 μg/kg i. v.) and the selective α₂-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 μg/kg, i. v.), a selective α₁-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 N^G -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 α₁-adrenergic and 5-HT_2A receptor blockade but not to the release of nitric oxide (NO) from vascular endothelium, to an α₂-adrenoceptor antagonism or to a calcium antagonist activity.

Abbreviations

BP:blood pressure

HR:heart rate

5-HT:5-hydroxytryptamine

i. v.:intravenous

L-NOARG:N^G -nitro-L-arginine

MAP:mean arterial pressure

NO:nitric oxide

PE:phenylephrine

Key words

Anaesthetised normotensive rats - bradycardia - hypotension - α-adrenoceptor antagonism - 5-HT_2A receptor blocking properties - (+)-nantenine - aporphine alkaloid

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