Mechanisms of prostaglandin E1-induced relaxation in penile resistance arteries.
OBJECTIVE
The current in vitro study was performed to investigate intracellular mechanisms underlying prostaglandin E1 (PGE1) elicited vasodilation in isolated penile resistance arteries and evaluate whether there may be interactions with the nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) pathway.


METHODS
Second or third order branches of the horse deep intracavernous penile artery were mounted in microvascular myographs. The vasodilator effects of PGE1 and cyclic adenosine 3',5'-monophosphate (cAMP) elevating agents were evaluated in the absence and the presence of inhibitors of the adenylate cyclase/cAMP and the NO/cGMP pathways.


RESULTS
PGE1, the adenylate cyclase activator forskolin, and the phosphodiesterase types 3 and 4 inhibitors milrinone and rolipram, respectively, dose dependently relaxed penile resistance arteries with rolipram being the most potent of the 4 relaxant agents. Threshold concentrations of rolipram markedly enhanced PGE1 elicited relaxations. The inhibition of cAMP dependent protein kinase decreased relaxant responses to PGE1, forskolin and rolipram. Neither mechanical endothelial cell removal nor the blockade of NO synthase or guanylate cyclase altered PGE1 relaxant responses. However, combined treatment with blockers of cAMP dependent protein kinase and cGMP dependent protein kinase unmasked an inhibitory effect of the latter on relaxations induced by PGE1 and forskolin.


CONCLUSIONS
These results provide evidence for cAMP involvement in PGE1 elicited vasodilation of penile resistance arteries. They underline the importance of the adenylate cyclase/cAMP pathway in the relaxation of penile erectile tissue. Moreover, cAMP elevating agents seem to cross-activate cGMP dependent protein kinase, thus, interacting downstream with the NO/cGMP cascade.
Ruiz Rubio
José L
JL
Departmento de Fisiología, Facultad de Farmacia, Universidad Complutense and Departmento de Urología, Hospital Universitario Ramón y Cajal, Madrid, Spain.
Hernández
Medardo
M
Rivera de los Arcos
Luis
L
Martínez
A Cristina
AC
García-Sacristán
Albino
A
Prieto
Dolores
D
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D006152:Cyclic GMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006736:Horses; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D010413:Penis / Q000098:blood supply*; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology
D009569:Nitric Oxide; D000527:Alprostadil; D006152:Cyclic GMP