Cardiovascular effects of agmatine, a "clonidine-displacing substance", in conscious rabbits.
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 alpha 2-adrenoceptors. In conscious rabbits, agmatine 10 micrograms kg-1 injected intracisternally (i.c.) caused no change, whereas agmatine 30, 100 and 300 micrograms kg-1 i.c. 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 micrograms kg-1 i.c. caused no change, whereas yohimbine 5, 15 and 50 micrograms 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 microM 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 microM. Agmatine did not change the basal efflux of tritium. The results show that agmatine, like yohimbine, causes central sympathoexcitation 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 brain cortex. alpha 2-Adrenoceptors, therefore, are probably not involved in its cardiovascular effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Szabo
B
B
Pharmakologisches Institut, Albert-Ludwigs-Universität, Freiburg, Germany.
Urban
R
R
Limberger
N
N
Starke
K
K
D000200:Action Potentials / Q000187:drug effects; D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002946:Cisterna Magna; D003000:Clonidine / Q000493:pharmacokinetics*; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007267:Injections; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008297:Male; D011817:Rabbits; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D000376:Agmatine; D003000:Clonidine