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Differential contributions of nitric oxide synthase isoforms at hippocampal formation to negative feedback regulation of penile erection in the rat
Author(s) -
Chang Alice Y. W.,
Chan Julie Y. H.,
Chan Samuel H. H.
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704657
Subject(s) - hippocampal formation , microinjection , papaverine , chemistry , nitric oxide synthase , nitric oxide , endocrinology , medicine
We established previously that a novel negative feedback mechanism for the regulation of penile erection, which is triggered by ascending sensory inputs initiated by tumescence of the penis, exists in the hippocampal formation (HF). This study further evaluated the participation of nitric oxide (NO) and the contribution of nitric oxide synthase (NOS) isoforms at the HF in this process. Adult, male Sprague‐Dawley rats that were anaesthetized and maintained with chloral hydrate were used, and intracavernous pressure (ICP) recorded from the corpus cavernosum of the penis was employed as our experimental index for penile erection. Microinjection bilaterally of a NO donor, S‐nitroso‐ N ‐acetylpenicillamine (0.25 or 1 nmoles), or the NO precursor, L ‐arginine (1 or 5 nmoles), into the hippocampal CA1 or CA3 subfield or dentate gyrus elicited a significant reduction in baseline ICP. Bilateral hippocampal application of a NO trapping agent, 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl‐3‐oxide (10 nmoles), significantly potentiated the elevation in ICP induced by intracavernous administration of papaverine (400 μg). Microinjection bilaterally into the HF of equimolar doses (0.5 or 2.5 pmoles) of two selective neuronal NOS inhibitors, 7‐nitroindazole or N ω ‐propyl‐ L ‐arginine; or equimolar doses (50 or 250 pmoles) of two selective inducible NOS inhibitors, aminoguanidine or S‐methylisothiourea, significantly enhanced the magnitude and/or duration of the papaverine‐induced elevation in ICP. In contrast, hippocampal application of a potent endothelial NOS inhibitor, N 5 ‐(1‐iminoethyl)‐ L ‐ornithine (18 or 92 nmoles), was ineffective. Neither of these inhibitors, furthermore, affected baseline ICP. These results suggest that NO generated via both neuronal and inducible NOS at the HF may participate in negative feedback regulation of penile erection.British Journal of Pharmacology (2002) 136 , 1–8; doi: 10.1038/sj.bjp.0704657