CARDIOVASCULAR EFFECTS OF AGMATINE, A CLONIDINE-DISPLACING SUBSTANCE,IN CONSCIOUS RABBITS

Agmatine has been identified as a ''clonidine-displacing substance'' i n extracts from bovine brain. We studied its effect on cardiovascular regulation and the role played in this effect by alpha(2)-adrenoceptor s. In conscious rabbits, agmatine 10 mu g kg(-1) injected intracistern ally (i.c.) caused no change, whereas agmatine 30, 100 and 300 mu g kg (-1) i.c. increased renal sympathetic nerve firing, the plasma concent ration of noradrenaline and adrenaline and arterial blood pressure. He art rate tended to be decreased. Yohimbine 1.5 mu g kg(-1) i.c. caused no change, whereas yohimbine 5, 15 and 50 mu g 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 [H-3]-noradrenaline, agmatine 1 to 100 mu M did not modify the electrically evoked overflow of tritium (either 4 p ulses 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 3 0 nM (4 pulses at 100 Hz), and this inhibition was not affected by agm atine 10 and 100 mu M. Agmatine did not change the basal efflux of tri tium. The results show that agmatine, like yohimbine, causes central s ympathoexcitation when given i.c., 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 alpha(2)-autoreceptors in rabbit b rain cortex. alpha(2)-Adrenoceptors, therefore, are probably not invol ved 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.