Contribution of cGMP but not peroxynitrite to negative feedback regulation of penile erection elicited by nitric oxide in the hippocampal formation of the rat

• Published in: Neuropharmacology 2004, Vol.46 (1), p.126-132
• Main Authors: Chan, J.Y.H., Chan, S.H.H., Chang, A.Y.W.
• Format: Article
• Language: English
• Subjects: Aminoquinolines - pharmacology; Animals; Cyclic GMP - analogs & derivatives; Cyclic GMP - pharmacology; Cyclic GMP - physiology; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Activators - pharmacology; Enzyme Inhibitors - pharmacology; Feedback - physiology; Hippocampal formation; Hippocampus - drug effects; Hippocampus - physiology; Indazoles - pharmacology; Intracavernous pressure; Male; Microinjections; Negative feedback regulation of penile erection; Nitric oxide; Nitric Oxide - physiology; Penile Erection - drug effects; Peroxynitrite; Peroxynitrous Acid - physiology; Rats; Rats, Sprague-Dawley; Soluble guanylyl cyclase/cGMP cascade; Venous Pressure - drug effects
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(03)00303-4

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.