Endoluminal norepinephrine inhibits smooth muscle activity of the pig pyeloureter by stimulation of beta-adrenoceptors without side effects.
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 microg/ml). In group B, pelvis was perfused with 6 ml/min. norepinephrine solutions (0, 0.001, 0.01, 0.1 and 1 microg/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 microg/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 beta-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.
Mortensen
Jens
J
Clinical Institute, University of Aarhus, Aarhus, Denmark. jmo@dadlnet.dk
Holst
Uffe
U
Jakobsen
Jørn Skibsted
JS
Andreasen
Frederik
F
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007682:Kidney Pelvis / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011312:Pressure; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D013015:Sotalol / Q000494:pharmacology; D013552:Swine; D014513:Ureter / Q000187:drug effects* / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D011943:Receptors, Adrenergic, beta; D013015:Sotalol; D009638:Norepinephrine; D010646:Phentolamine