Cardiovascular effects of agmatine, a “clonidine-displacing substance”, in conscious rabbits

Abstract

Agmatine has been identified as a “clonidine-displacing substance” in extracts from bovine brain. We studied its effect on cardiovascular regulation and the role played in this effect by α₂-adrenoceptors.

In conscious rabbits, agmatine 10 μg kg⁻¹ injected intracisternally (i.e.) caused no change, whereas agmatine 30, 100 and 300 μg kg⁻¹ i.e. increased renal sympathetic nerve firing, the plasma concentration of noradrenaline and adrenaline and arterial blood pressure. Heart rate tended to be decreased. Yohimbine 1.5 μg kg⁻¹ i.e. caused no change, whereas yohimbine 5, 15 and 50 μg kg⁻¹ increased renal sympathetic nerve activity, the plasma concentration of noradrenaline and adrenaline, blood pressure and heart rate. In rabbit brain cortex slices preincubated with [³H]-noradrenaline, agmatine 1 to 100 μM did not modify the electrically evoked overflow of tritium (either 4 pulses at 100 Hz or 36 pulses at 3 Hz). The evoked overflow was reduced by 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline (UK 14304) 0.03 to 30 nM (4 pulses at 100 Hz), and this inhibition was not affected by agmatine 10 and 100 μM. Agmatine did not change the basal efflux of tritium.

The results show that agmatine, like yohimbine, causes central sympathoexcitation when given i.e., but agmatine differs from yohimbine in that it does not increase heart rate. Agmatine acts neither as an agonist nor as an antagonist at the α₂-autoreceptors in rabbit brain cortex. α₂-Adrenoceptors, therefore, are probably not involved in its cardiovascular effects. An action at imidazoline receptors in the medulla oblongata or some other hitherto unknown mechanism may be responsible for the sympathoexcitation.