Enhanced contractility of rabbit corpus cavernosum smooth muscle by oxidized low density lipoproteins.
We have investigated the effect of oxidatively-modified low density lipoproteins (ox-LDL) on the contractility of rabbit trabecular smooth muscle. Low density lipoproteins (LDL) were isolated from fresh human plasma pooled from multiple donors and oxidized by exposure to copper. Corpus cavernosum strips from New Zealand White rabbits were studied in organ chambers for isometric tension measurement. Corporeal strips in which moderate tone was induced by phenylephrine, contracted when exposed to ox-LDL, but not when exposed to either native LDL (nLDL) or LDL protected from oxidation by butylated hydroxytoleune (BHT-LDL). Removal of the endothelium, or treatment of the corporeal strips with N(omega)-nitro-L-arginine (nitric oxide synthase inhibitor), methylene blue of LY83583 (guanylate cyclase inhibitors/superoxide producing agents), did not prevent ox-LDL-induced contraction. ox-LDL, dose-dependently, enhanced the contractile response of corporeal strips to low and moderate concentrations by phenylephrine. nLDL had no significant effect on phenylephrine-induced contraction of corporeal strips. ox-LDL, nLDL or BHT-LDL had no effect on relaxation induced by the endothelium-dependent dilator, acetylcholine, or the nitric oxide donor, nitroprusside. In conclusion, this present study demonstrates significant pro-contractile effects of ox-LDL on corporeal smooth muscle, this effect is independent of the endothelium or the nitric oxide/cGMP pathway. The pro-contractile effect of ox-LDL may interfere with penile smooth muscle relaxation, necessary for the initiation and maintenance of penile erection.
Ahn
T Y
TY
Department of Urology, Boston University School of Medicine, Massachusetts, USA.
Gómez-Coronado
D
D
Martínez
V
V
Cuevas
P
P
Goldstein
I
I
Sáenz de Tejada
I
I
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010413:Penis / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits
D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002084:Butylated Hydroxytoluene; D010656:Phenylephrine; D019335:Nitroarginine; D003300:Copper; C041715:6-anilino-5,8-quinolinedione; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D011188:Potassium