Endothelium-derived nitric oxide and cyclooxygenase products modulate corpus cavernosum smooth muscle tone.
Relaxation of penile corpus cavernosum smooth muscle is controlled by nerve and endothelium derived substances. In this study, endothelium-dependent relaxation of corporal smooth muscle was characterized and the role of arachidonic acid products of cyclooxygenase in endothelium-dependent relaxation was examined. Endothelium removal from rabbit corpora was performed by infusion with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate and was confirmed by transmission electron microscopy. Strips of human and rabbit corporal tissues were studied in the organ chambers for isometric tension measurement. The accumulation of cyclic guanosine monophosphate (cGMP) and the release of eicosanoids from corporal tissue was measured by radioimmunoassay and correlated to smooth muscle relaxation. Our study showed that relaxation of corpus cavernosum tissue to acetylcholine, bradykinin and substance P was endothelium-dependent; potentiated by indomethacin; and inhibited by NG-monomethyl-L-arginine, methylene blue or LY83583. Relaxation to papaverine and sodium nitroprusside was endothelium-independent, and unaffected by NG-monomethyl-L-arginine. Relaxation to vasoactive intestinal polypeptide was partially endothelium-dependent; potentiated by indomethacin; attenuated by NG-monomethyl-L-arginine or methylene blue. The tissue level of cGMP was enhanced by acetylcholine and nitric oxide. Methylene blue inhibited both basal and drug-stimulated levels of cGMP. The release of eicosanoids was enhanced by acetylcholine and blocked by indomethacin. In conclusion, nitric oxide or a closely related substance accounts for the activity of endothelium-derived relaxing factor in the corporal tissue. Inhibition of the release of eicosanoids potentiates the relaxing effect of nitric oxide. Nitric oxide increases tissue cGMP which appears to modulate corporal smooth muscle relaxation.
Department of Urology, Boston University Medical Center, Massachusetts.
K M
KM
Azadzoi
N
N
Kim
M L
ML
Brown
I
I
Goldstein
R A
RA
Cohen
I
I
Saenz de Tejada
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002793:Cholic Acids / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D010413:Penis / Q000378:metabolism / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011817:Rabbits; D013373:Substance P / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D002793:Cholic Acids; D015777:Eicosanoids; D018377:Neurotransmitter Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D010208:Papaverine; D011451:Prostaglandin-Endoperoxide Synthases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D000109:Acetylcholine; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate; D001920:Bradykinin; D007213:Indomethacin