Actions of endothelin on isolated corpus cavernosum from rabbit and man.
The effects of endothelin, a vasoconstrictor peptide produced by vascular endothelial cells, were investigated in isolated rabbit and human corpus cavernosum (CC). Preparations from both rabbit and man were potently contracted by endothelin in a concentration-dependent manner. The contractions developed slowly, could not be reversed despite frequent washings, and were only partly inhibited by the Ca2+ channel blocker nimodipine. Even in Ca2(+)-free medium containing the chelator EGTA a small contractile component persisted. In rabbit CC, the contractions in Ca2(+)-free medium were not affected by nimodipine, the Ca2(-)-channel agonist BAY K 86(44), or by depletion of intracellular Ca2(+) stores sensitive to noradrenaline (NA) and caffeine, but were almost abolished by the protein kinase C inhibitor H7. In both rabbit and man, carbachol and vasoactive intestinal polypeptide concentration-dependently relaxed preparations contracted by endothelin. The relaxations induced by carbachol were antagonized by atropine. Endothelin enhanced concentration-dependently the contractions induced by exogenously applied NA in rabbit CC. The enhancement was more pronounced at low concentrations of NA. This study shows that endothelin potently contracts isolated penile erectile tissue. The contraction seems to be mediated mainly by influx of Ca2+ through the cell membrane, which partly occurs through a pathway other than voltage-operated calcium channels. However, involvement of other mechanisms cannot be excluded. The results suggest that endothelin can play a role in penile erectile mechanisms.
Department of Clinical Pharmacology, University Hospital of Lund, Sweden.
F
F
Holmquist
K E
KE
Andersson
H
H
Hedlund
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009553:Nimodipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009994:Osmolar Concentration; D010413:Penis / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D016232:Endothelins; D010455:Peptides; D014660:Vasoactive Intestinal Peptide; D009553:Nimodipine; D002217:Carbachol; D009638:Norepinephrine