Effects of various nitric oxide-donating drugs on adrenergic tension of human seminal vesicles in vitro.
OBJECTIVE
To evaluate the effects of the nitric oxide (NO)-donating compounds sodium nitroprusside (SNP), S-nitroso-glutathione (GSNO), S-nitroso-N-acetylcysteine (SNAC), S-nitroso-N-acetylcysteine-ethylester (SNACET), and linsidomine (SIN-1) on the adrenergic tension of isolated human seminal vesicle strip preparations. The significance of the NO-cyclic guanosine monophosphate (cGMP) pathway in the regulation of smooth muscle tone in the human genitourinary tract has been well established. However, information on the significance of NO-mediated signal transduction in the functional control of the mammalian seminal vesicles is still sparse.


METHODS
Seminal vesicle strip preparations were applied to an organ bath system under standard conditions. Tension was induced by the addition of 10 microM norepinephrine. After stable tension plateaus had been reached, the drugs were added in a cumulative manner (0.01 to 100 microM) and the isometric responses of the tissue registered. The effects of the compounds on the phasic contractility of the tissue preparations were also evaluated. The adenylyl cyclase-stimulating agent forskolin was used as a reference compound known to interfere with the cyclic adenosine monophosphate pathway.


RESULTS
Adrenergic tension was dose dependently attenuated by the drugs. The rank order of potency, from greater to lesser, was GSNO, SNAC, SNP, SIN-1, forskolin, and SNACET. The rank order (from greater to lesser) with regard to the inhibitory effects of the compounds on the frequency of phasic contractions of the tissue induced by the addition of norepinephrine was GSNO, SNAC, SNP, and SIN-1; the effects of SIN-1, forskolin, and SNACET on the frequency of contractions were nearly equipotent.


CONCLUSIONS
Our results strongly support the hypothesis that the contractility of the human seminal vesicle is under the control of the NO-cGMP pathway. This finding may give a rationale for the use of S-nitrosothiols, such as GSNO and SNAC, in the pharmacotherapy of hyperexcitatory disturbances of ejaculation (premature ejaculation).
Machtens
Stefan
S
Department of Urology, Hannover Medical School, Hannover, Germany.
Ckert
Stefan
S
Stief
Christian G
CG
Tsikas
Dimitrios
D
Frlich
J rgen C
Jr
Jonas
Udo
U
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000368:Aged; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D004542:Ejaculation / Q000187:drug effects; D007172:Erectile Dysfunction / Q000188:drug therapy; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D012669:Seminal Vesicles / Q000187:drug effects* / Q000502:physiology; D012735:Sexual Dysfunction, Physiological / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D005576:Colforsin; D026422:S-Nitrosoglutathione; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; D008981:Molsidomine; D006152:Cyclic GMP; D009638:Norepinephrine