[In vitro study of the modulation of human ureteral tonus by nitric oxide and zaprinast, a phosphodiesterase inhibitor].
OBJECTIVE
To assess the role of nitric oxide (NO) and its second messenger, cGMP, on the mechanisms underlying human ureteral smooth muscle relaxation.


METHODS
Proximal segments of ureter were dissected from nephrectomy, then cut into rings and suspended in organ chambers. Isometric tone was recorded at baseline and after preincubation with KCl (120 mumol). The Increasing concentration (10-8-10-4 M) of NO donors, Sodium nitroprusside, (SNP) and molsidomine (SIN-1) and a type V phosphodiesterase inhibitor, Zaprinast were added to the organ chambers and a dose response curve was constructed from each experiment.


RESULTS
Dose-dependent relaxation was seen with all compounds. This was, however, more pronounced with SNP as compared with SIN-1. Zaprinast alone had marginal relaxant effect but markedly potentiated the relaxing effect of the NO donor SNP (p < 0.05). Inhibition of NO synthesis by the arginine analogue L-NA increased electrical-induced contraction (98 +/- 4% vs 122 +/- 3%, p < 0.001).


CONCLUSIONS
Activation of the soluble guanylate cyclase by NO donors markedly relaxed significantly human ureteral smooth muscle but inhibition of phosphodiesterase did not affect the in vitro relaxation. Our results suggest that cGMP is an important second messenger in the transduction signalling pathway leading to relaxation of human ureteral smooth muscle. By contrast, basal activity of phosphodiesterase seems to be marginal under physiological condition.
Saighi
D
D
Service d'Urologie, CHU Cochin, Paris, France. d.saighi@wanadoo.fr
Zerbib
M
M
Thiounn
N
N
Flam
T
T
Conquy
S
S
Jacob
L
L
Dall'Ava-Santucci
J
J
Debré
B
B
Dinh-Xuan
A T
AT
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000494:pharmacology*; D004558:Electric Stimulation; D006801:Humans; D066298:In Vitro Techniques; D009129:Muscle Tonus / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D011688:Purinones / Q000494:pharmacology*; D014513:Ureter / Q000187:drug effects* / Q000502:physiology
D011688:Purinones; D009569:Nitric Oxide; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast
Etude in vitro de la modulation du tonus urétéral humain par le monoxyde d'azote et un inhibiteur des phosphodiestérases, le zaprinast.