The effects of drugs on pacemaker regions of isolated rabbit renal pelvis

Acetylcholine failed to change the frequency of spontaneous contractions in the proximal region of isolated rabbit renal pelvis, but significantly increased the contractile frequency in the middle and distal regions, which then reached similar levels to those of the proximal region. Pretreatment with reserpine caused a decrease in the frequency of spontaneous contractions in the proximal, but not in the middle or distal regions. Reserpine-pretreated tissues developed hypersensitivity to catecholamines, while acetylcholine produced effects similar to those observed in control preparations. Atropine and N-methyl-scopolamine antagonized the action of acetylcholine in both the middle and the distal regions, suggesting that the action was exerted through muscarinic receptors. Adrenaline and alpha-stimulating drugs, but not isoprenaline, significantly increased the contractile frequency of all three tissues: the increase in the proximal region reached levels in excess of its fundamental maximal frequency. Phentolamine caused a significant decrease in the frequency of the proximal region and fully inhibited the stimulating action of catecholamines, indicating that this stimulation was mediated by alpha-adrenoceptors. The myogenic nature of pacemaking cells was confirmed by the effect of tetrodotoxin, ouabain and verapamil. The decrease in frequency in the pacemaker region of the proximal pelvis whether caused by reserpine or phentolamine indicates a significant role of catecholamines in modulating pacemaker activity.