Contribution of cGMP but not peroxynitrite to negative feedback regulation of penile erection elicited by nitric oxide in the hippocampal formation of the rat.
We established previously that nitric oxide (NO) in the hippocampal formation (HF) participates actively in negative feedback regulation of penile erection. This study further evaluated whether this process engaged soluble guanylyl cyclase (sGC)/cGMP cascade or peroxynitrite in the HF. Intracavernous pressure (ICP) recorded from the penis in adult, male Sprague-Dawley rats anesthetized with chloral hydrate was employed as our experimental index for penile erection. Microinjection bilaterally of a NO-independent sGC activator, YC-1 (0.1 or 1 nmol) or a cGMP analog, 8-Bromo-cGMP (0.1 or 1 nmol), into the HF elicited a significant reduction in baseline ICP. Bilateral application into the HF of equimolar doses (0.5 or 1 nmol) of a sGC inhibitor, LY83583 or a NO-sensitive sGC inhibitor, ODQ significantly antagonized the decrease in baseline ICP induced by co-administration of the NO precursor, L-arginine (5 nmol), along with significant enhancement of the magnitude of papaverine-induced elevation in ICP. In contrast, a peroxynitrite scavenger, L-cysteine (50 or 100 pmol), or an active peroxynitrite decomposition catalyst, 5,10,15,20-tetrakis-(N-methyl-4'-pyridyl)-porphyrinato iron (III) (10 or 50 pmol), was ineffective in both events. These results suggest that NO may participate in negative feedback regulation of penile erection by activating the sGC/cGMP cascade in the HF selectively.
Chan
J Y H
JY
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, ROC.
Chan
S H H
SH
Chang
A Y W
AY
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005246:Feedback / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009569:Nitric Oxide / Q000502:physiology*; D010410:Penile Erection / Q000187:drug effects*; D030421:Peroxynitrous Acid / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014690:Venous Pressure / Q000187:drug effects
D000634:Aminoquinolines; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D007191:Indazoles; D030421:Peroxynitrous Acid; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C041715:6-anilino-5,8-quinolinedione; D006152:Cyclic GMP