Involvement of L-arginine/nitric oxide pathway at the paraventricular nucleus of hypothalamus in central neural regulation of penile erection in the rat

Abstract

The objective of this study is to investigate whether the L-arginine=nitric oxide pathway is involved in the neurotransmission of paraventricular nucleus of hypothalamus (PVN) activation-induced penile erection in the rat. Male adult Sprague-Dawley rats anesthetized with pentobarbital were used. The femoral artery was cannulated to measure systemic and mean arterial pressure (SAP and MAP), and heart rate (HR). A 26-gauge needle was inserted into corpus cavernosum to measure the intracavernous pressure (ICP) simultaneously with SAP, MAP and HR on a polygraph. Four groups of study were arranged: (1) stereotaxically delivery of L-arginine (500 nmol=500 nl) into PVN; (2) administration of a mixture (1 ml) containing N G -Nitro-L-arginine methyl ester (L-NAME) 500 nmol and L-arginine 500 nmol into PVN; (3) microinjection of saline 500 nl into PVN as a vehicle control; and (4) intracavernous injection of L-arginine (100 nmol= 50 ml). The ICP, SAP, MAP and HR were monitored for at least 2 h after each administration of the experimental agents. Upon administration of L-arginine into PVN, there was a significant increase of ICP from resting 9.6 AE 2.5 mmHg to peaked at 64.4 AE 9.8 mmHg after a latency of 3016.0 AE 1749.7 s and with a duration of 27.6 AE 15.8 min. There was no change of resting ICP after administration of the mixture of L-NAME and L-arginine into PVN. Application of saline to PVN and intracavernous injection of L-arginine failed to increase ICP. Based on elicitation of penile erection upon administration of L-arginine into PVN, and elimination of this L-arginine induced penile erection by co-administration of L-NAME with L-arginine, the results of this study suggest that L-arginine=nitric oxide pathway may be involved in the neurotransmission of PVN activation-induced penile erection in the rat.

Erectile Function and Sexual Behavior: A Review of the Role of Nitric Oxide in the Central Nervous System

“…These findings confirm that l -arginine-induced penile erection is mediated by its conversion to NO because of the selective substrate stereospecificity of NO synthase (e.g., the l -amino acid only is converted to NO and citrulline). In line with these studies l -arginine (500 nmol/0.5µL) injected into the PVN (i) increases intracavernous blood pressure in male rats kept under pentobarbital anesthesia [ 43 ], (ii) increases reflex penile erections in awake rats [ 42 ], and (iii) both these responses were abolished by the concomitant administration of L-NAME (500 nmol) [ 42 , 43 ]. At variance from l -arginine, nitroglycerin is able to induce penile erection either when given i.c.v.…”

“…NO synthase was also detected and found involved in the activation of luteinizing hormone-releasing hormone (LH-RH) neurons in the medial preoptic area ([ 31 ] and references therein). The localization of a Ca 2+ -dependent NO synthase in PVN oxytocinergic neurons [ 8 ] in close proximity with dopamine [ 32 , 33 ], serotonin (5-HT) [ 34 ] and excitatory amino acid projections [ 35 ] and the above-mentioned possible involvement of NO in the release of CRH that controls corticotrophin (ACTH) release, and of LH-RH that control the release of both follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the adenohypophysis, led the authors of this review and other research groups to investigate on a possible role of NO in the central control of erectile function and sexual behavior first in the PVN [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] and in the medial preoptic area [ 44 , 45 ] and later in other brain areas. It is now clear that NO plays a role in the control of erectile function and sexual behavior not only at the hypothalamic and medial preoptic area level, but also in other extrahypothalamic brain areas.…”

Animal models of erectile dysfunction

“…[ 18 ] Penile erection is recorded after giving electric or chemical stimulation. [ 19 ] This model is of great value to elicit the role of various neurotransmitters involved in penile erection.…”

Projections from bed nuclei of the stria terminalis, magnocellular nucleus: Implications for cerebral hemisphere regulation of micturition, defecation, and penile erection

“…Abundant evidence implicates Barrington's nucleus and the paraventricular nucleus in control of micturition (for reviews see Appenzeller, 1990;de Groat and Steers, 1990;Blok and Holstege, 1996;de Groat, 1998;Holstege, 1998) and penile erection (e.g., Chen and Chang, 2002;Giuliano and Rampin, 2000;Rampin and Giuliano, 2000;Sachs, 2000;Steers, 2000;Melis et al, 2001). Recently, these two nuclei also have been implicated in the coordination of colonic functions like defecation (Pavcovich et al, 1998;Vizzard et al, 2000).…”