Nitrergic Control of Peripheral Sympathetic Responses in the Human Corpus Cavernosum: A Comparison with Other Species

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 15; pp. 8226 - 8231
• Main Authors: Cellek, Selim, Moncada, Salvador
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 22.07.1997; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Animals; Biological Sciences; Cocaine; Drug interactions; Electric Stimulation; Guanethidine - pharmacology; Histamines; Humans; Innervation; Male; Medical research; Mice; Muscle Contraction - drug effects; Muscle tonus; Muscle, Smooth - innervation; Muscle, Smooth - physiology; Muscles; Muscular system; Nerves; Nervous system; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - physiology; Nitroarginine - pharmacology; Norepinephrine; Norepinephrine - antagonists & inhibitors; Norepinephrine - pharmacology; Original recordings; Oxadiazoles - pharmacology; Oxyhemoglobins - pharmacology; Penis - innervation; Penis - physiology; Pharmaceuticals; Pharmacology; Quinoxalines - pharmacology; Rabbits; Rats; Species Specificity; Sympathetic Nervous System - physiology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.15.8226

Noradrenergic contractions induced by electrical field stimulation (EFS) of the rabbit anococcygeus muscle and the human and rabbit corpus cavernosum did not occur until termination of stimulation, even when EFS was applied for long periods (10 min). After treatment with a nitric oxide synthase inhibitor, a scavenger of NO, or a specific inhibitor of the soluble guanylate cyclase, EFS-induced contraction began as soon as stimulation commenced and its magnitude and duration were increased. In the presence of a cGMP-phosphodiesterase inhibitor, the lag period between the end of EFS and the onset of contraction was longer, and the response was smaller. Even when the concentration of endogenous noradrenaline was increased with cocaine, the contraction still did not occur during EFS and the lag period was unchanged, although the response was enhanced. When tissue tone was elevated, relaxation occurred during EFS followed by a contraction. After blockade of neuronal noradrenaline release with guanethidine, contractions of the tissues to increasing concentrations of exogenous noradrenaline were significantly reduced by EFS, an effect that was reversible by inhibition of NO synthase. In contrast, in the rat and mouse anococcygeus muscles contraction began immediately with EFS, and nitrergic stimulation by EFS did not affect the responses elicited by high concentrations of exogenous noradrenaline. These results suggest that the human and rabbit genitourinary organs have a powerful nitrergic innervation that does not merely modulate, but actually controls, the sympathetic responses. Our observations may increase understanding of the balance between nitrergic and sympathetic systems in humans, disruption of which may contribute to certain pathological conditions.