Endoluminal Norepinephrine Inhibits Smooth Muscle Activity of the Pig Pyeloureter by Stimulation of β‐Adrenoceptors without Side Effects

Abstract

It has been demonstrated in pigs that endoluminal administration of norepinephrine reduces the increase in renal pelvic pressure during perfusion. The purposes were to describe concentration-response relationship and receptor mechanism of the effect of norepinephrine on muscle function of pyeloureter and to reveal possible side effects on cardiovascular and renal functions. Renal pelvis was perfused, while pelvic pressure, cardiovascular and renal functional parameters were recorded. In group A, a pelvic pressure increase was examined during pressure flow studies with norepinephrine solutions (0, 1, 5, 50 and 100 μ g/ml). In group B, pelvis was perfused with 6 ml/min. norepinephrine solutions (0, 0.001, 0.01, 0.1 and 1 μ g/ml). In group C, pelvis was perfused with 6 ml/min. norepinephrine, norepinephrine + sotalol 10 -6 mol/l and norepinephrine + phentolamine 10 -6 mol/l. Norepinephrine solutions of 0, 10 -8 , 10 -7 , 10 -6 , 10 -5 and 10 -4 mol/l were used. In group A, all norepinephrine solutions lowered the pelvic pressure increase significantly. Large increases in plasma and urine norepinephrine occurred with 50 and 100 μ g/ml, but cardiovascular and renal functions remained unchanged. In group B, a significant diminishing pelvic pressure increase with all solutions was seen with a significant difference between all solutions. In group C, norepinephrine demonstrated a concentration-response curve with EC 50 between 10 -8 and 10-7 mol/l (10 -7.27 ± 0.40 ). Sotalol had a smooth muscle inhibitory effect on the pyeloureter and inhibited the effect of norepinephrine increasing EC 50 by about a factor 10 (10 -6.40 ± 1.17 ). No convincing effect of phentolamine was observed. Endoluminal norepinephrine probably stimulates β -adrenoceptors and inhibits a renal pelvis pressure increase to perfusion in a dose-related way without side effects. Endoluminal norepinephrine is safe in pigs and may be useful under endoscopy of the pyeloureter.Our previous studies [1,2] have shown that endoluminal norepinephrine diminishes a pressure increase to perfusion in the renal pelvis of the pig. The significant decrease of the pressure flow relationship [3,4] was obtained without systemic side effects [1]. The literature on this topic is sparse. The findings in two other studies [5,6] apparently are in contrast with ours, but the explanation may purely be differing experimental conditions. Selmy et al .[5] perfused renal pelvis with norepinephrine at a concentration of 100 μ g/ml using a flow rate of 2 ml/min. and found some increases in pelvic pressure and ureteral peristaltic frequency. Danuser et al . [6] perfused renal pelvis with phenylepinephrine at concentrations of 0.1-3 mg/ml using a flow rate of 0.5 ml/min. and found increased peristaltic frequency and amplitude in the mid-portion of the ureter. We used unphysiological high flow rates [1,2] to examine the effect of norepinephrine while performing a provocative test of the pyeloureter, and we found that the weakest norepinephrine concentration of 5 μ g/ml exerts a m...

Endoluminal isoproterenol reduces renal pelvic pressure during semirigid ureterorenoscopy: a porcine model

“…[11] showed that noradrenaline has a relaxing potency on the tension of the human ureter induced by KCl. The relaxing potency of noradrenaline has been confirmed in other studies [16,17]. Wanajo et al.…”

“…Although the effect on α -adrenoceptors is predominant, Park et al [11] showed that noradrenaline has a relaxing potency on the tension of the human ureter induced by KCl. The relaxing potency of noradrenaline has been confirmed in other studies [16,17]. Wanajo et al [12] showed that various β -adrenoceptor agonists (salbutamol, procaterol and terbutaline) relaxed the KCl-induced tonic contractions in isolated porcine ureteric preparations, as did the two β 3 -adrenoceptor agonists CL-316243 and CGP-12177A.…”