Pharmacological modulation of ureteric peristalsis in a chronically instrumented conscious pig model: effect of adrenergic and nitrergic modulation.
OBJECTIVE
To evaluate the role of adrenergic and nitrergic signaling on ureteric peristaltic frequency and contraction force in vivo using a large animal model.


METHODS
Twelve female pigs (72 ± 4 kg) were chronically instrumented with an electronic pressure-monitoring catheter in the right ureter. Nephrostomy, cystostomy, and arterial and venous catheters were left in situ. Ureteral peristalsis was recorded before and after the administration of propranolol, isoprenaline, doxazosin, urapidil, phenylephrine, LNNA (Nω-nitro-L-arginine), and L-arginine.


RESULTS
α1-Adrenergic receptor stimulation resulted in an increased P max and peristaltic frequency. However, α1-inhibition decreased P max alone. Similarly, β-adrenergic stimulation decreased P max and peristaltic frequency, whereas β-inhibition increased only P max. LNNA administration increased P max in the distal ureter and hydrostatic pressure in the pyelocalyceal system. L-Arginine did not affect P max or frequency, but resulted in a significantly higher diuresis. Either agonist or antagonist of NO did not affect peristaltic frequency and length of contraction.


CONCLUSIONS
Activation of α- and β-adrenergic receptors, respectively, stimulates and inhibits ureteric peristalsis. The biological effect of NO on ureteric motility is regionally determined and corresponds to the distribution of NOS-positive nerves. Inhibition of NOS activity increases P max in the distal ureter and tonic activity of the ureteric muscle resulting in higher hydrostatic pressure in the renal pelvis.
Department of Urology, Haga Teaching Hospital, The Hague, The Netherlands.
H
H
Roshani
HagaZiekenhuis, Leyweg 275, The Hague, The Netherlands. saskiaweltings@gmail.com.|Department of Urology, Haga Teaching Hospital, The Hague, The Netherlands. saskiaweltings@gmail.com.
S
S
Weltings
Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
N F
NF
Dabhoiwala
Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
W H
WH
Lamers
D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D003243:Consciousness; D005260:Female; D023421:Models, Animal; D019335:Nitroarginine / Q000494:pharmacology*; D010528:Peristalsis / Q000187:drug effects*; D000071756:Soluble Guanylyl Cyclase / Q000187:drug effects*; D013552:Swine; D014513:Ureter / Q000187:drug effects* / Q000502:physiology*
D018663:Adrenergic Agents; D019335:Nitroarginine; D001120:Arginine; D000071756:Soluble Guanylyl Cyclase
Adrenergic; Motility; Nitrergic; Peristalsis; Ureter