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)
Cardiovascular and sympathetic nervous system effects of the mixed alpha 2-adrenoceptor and imidazoline receptor agonist rilmenidine were studied in conscious rabbits chronically instrumented for the recording of the firing rate of renal sympathetic fibers. Separate experiments were carried out on pithed rabbits with electrically stimulated (2 Hz) sympathetic outflow. Drugs were administered intravenously in a cumulative manner. In conscious rabbits, rilmenidine 0.1, 0.3 and 1.0 mg kg-1 dose-dependently lowered blood pressure, renal sympathetic nerve activity, heart rate and the plasma concentration of noradrenaline and adrenaline. The effect on blood pressure and plasma catecholamines was maximal after 0.3 mg kg-1 whereas heart rate and renal sympathetic nerve activity decreased further after rilmenidine 1.0 mg kg-1. Yohimbine 0.1 and 0.5 mg kg-1, when injected subsequently, attenuated and at the higher dose abolished all effects of rilmenidine. The effects of rilmenidine were also antagonized by the alpha 2-adrenoceptor antagonist 2-(2,3-dihydro-2-methoxy-1,4-benzodioxin-2-yl)-4,5-dihydro-1H-imid azole HCl (RX821002; 0.1 and 0.5 mg kg-1). Yohimbine 0.1 and 0.5 mg kg-1 did not attenuate or attenuated only slightly the decrease of heart rate and renal sympathetic nerve activity produced by infusion of vasopressin. In pithed rabbits with electrically-stimulated sympathetic outflow, yohimbine 0.1 submaximally and yohimbine 0.5 mg kg-1 maximally increased the plasma noradrenaline concentration. The experiments show by direct measurement of sympathetic nerve firing and plasma catecholamines that rilmenidine causes sympathoinhibition in conscious rabbits, presumably through central sites of action.(ABSTRACT TRUNCATED AT 250 WORDS)
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