Effects of arginase inhibitors on the contractile and relaxant responses of isolated human penile erectile tissue.
OBJECTIVE
An impairment in the local availability of nitric oxide (NO) may impair male erectile function. The activity of l-arginine-degrading arginase enzymes may attenuate the relaxation of cavernous smooth muscle by reducing local NO production. Arginase enzymes compete with the nitric oxide synthases for the common substrate, the amino acid l-arginine. Very little data are available regarding the significance of arginase enzymes in the control of human penile erectile tissue. The aim of the present study was to elucidate the effects of drugs known to inhibit arginase activity on the relaxation of isolated human corpus cavernosum (HCC) and the production of cyclic GMP.


METHODS
Using the organ bath technique, the effects of the arginase inhibitors DFMO, H-Orn-OH·HCl, H-lle-OH and nor-NOHA (10 nM–10 μM) on the tension induced by NE (1 μM) and the relaxation induced by electrical field stimulation (EFS) of HCC were investigated. HCC strips were also exposed to increasing concentrations of the compounds, and the production of cGMP was determined by means of a radioimmunoassay.


RESULTS
Only marginal effects of the arginase inhibitors were registered on the tension induced by NE and the relaxation exerted by EFS. Mean reversion of tension ranged from 18 to 8%. Only DFMO and nor-NOHA amplified the EFS-induced relaxation by 11 and 29%, respectively. These effects were not paralleled by an increase in tissue levels of cGMP.


CONCLUSIONS
Arginase inhibitors appeared to be ineffective in reversing the adrenergic tension and increasing the electrically induced relaxation of isolated HCC.
Department of Urology and Uro-Oncology, Hannover Medical School, 30625 Hannover, Germany. j.m.lorenzen@gmail.com
Johan M
JM
Lorenzen
Stefan
S
Ückert
Friedemann
F
Scheller
Hermann
H
Haller
Markus A
MA
Kuczyk
D000328:Adult; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D009924:Organ Culture Techniques; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D010413:Penis / Q000187:drug effects / Q000502:physiology; D057829:Gender-Affirming Procedures; D055815:Young Adult
D004791:Enzyme Inhibitors; C404735:N(omega)-hydroxynorarginine; D009569:Nitric Oxide; D001120:Arginine; D001119:Arginase; D006152:Cyclic GMP; D000518:Eflornithine