Relative roles of cyclooxygenase and nitric oxide synthase pathways in ischemia-induced increased contraction of cavernosal smooth muscle

Purpose: To study the mechanism of chronic ischemia-induced increased caver nosal smooth muscle contraction in an animal model of vasculogenic erectile dysfunction. Materials and Methods: New Zealand White rabbits were divided into control (n = 6, fed with a regular diet), hypercholesterolemic (n = 9, fed with a d iet containing 0.5% cholesterol) and chronic cavernosal ischemia (CCI, n = 10, underwent balloon de-endothelialization of iliac arteries and received a diet containing 0.5% cholesterol) groups, After 16 weeks, the relationshi p between iliac artery blood flow and cavernosal smooth muscle contraction was studied. The roles of cyclooxygenase and nitric oxide (NO) pathways in chronic ischemia-induced increased smooth muscle contraction were also exam ined. Results: Iliac artery blood flow in the CCI group was significantly reduced compared with the control and hypercholesterolemic groups. Hypercholestero lemia alone did not affect cavernosal smooth muscle contraction. Atheroscle rosis-induced chronic cavernosal arterial insufficiency did not affect cont raction to norepinephrine while causing a significant increase in electrica l field stimulation-induced neurogenic contraction. Inhibition of the cyclo oxygenase pathway by indomethacin decreased electrical field stimulation-in duced contraction in all animals but failed to normalize the differences be tween CCI and control groups. In the presence of indomethacin, L-arginine d ecreased electrical field stimulation-induced contraction in the control an d hypercholesterolemic groups but not in the CCI group. In the presence of indomethacin, treatment with nitric oxide synthase (NOS) inhibitor, N-G-mon omethyl-L-arginine (L-NMMA), increased electrical field stimulation-induced contraction in all groups. This effect of L-NMMA on smooth muscle contract ion was significantly greater in the control and hypercholesterolemic group s compared with the CCI group. After tissue treatment with L-NMMA, the magn itude of contraction in cavernosal tissue from control and hypercholesterol emic groups was similar to those observed in the CCI group. Conclusions: Mechanism of chronic ischemia-induced increased cavernosal smo oth muscle contraction involves increased output of constrictor eicosanoids and impairment of the inhibitory influence of NO pathway in cavernosal tis sue.