Effects of the nitric oxide synthase inhibitor N^G‐nitro‐L‐arginine on the erectile response to cavernous nerve stimulation in the rabbit

Abstract

Using a rabbit model, the involvement of the L-arginine/nitric oxide pathway in penile erection was investigated. The mean basal intracavernous pressure was 21 cm H2O. Cavernous nerve stimulation (4-8 V, 20-30 Hz) increased the pressure to approximately 130 cm H2O. This response was highly reproducible and usually associated with full penile erection. The pressure increase could be quantified in terms of: (1) the slope of the initial, ascending part of the pressure increase; (2) delta P, which was defined as the maximal pressure obtained by the stimulation minus the basal pressure before the stimulation; (3) T90, which was defined as the time to reach 90 per cent of delta P. Intrapenile administration of the L-arginine/nitric oxide synthesis inhibitor NG-nitro-L-arginine had no effect on systemic arterial blood pressure. However, NG-nitro-L-arginine (0.22 and 2.19 mg), administered via the same route, abolished the erectile response induced by cavernous nerve stimulation; T90 increased and slope and delta P decreased significantly. NG-nitro-D-arginine (2.19), on the other hand, had no inhibitory effect. L-arginine (21.07 mg), given either directly or after NG-nitro-L-arginine had no consistent effect on the functional response to cavernous nerve stimulation. The results suggest that pharmacologically induced effects on intracavernous pressure in the rabbit can be described quantitatively, and that this model may be useful to study the mechanisms controlling penile erection in vivo. The pronounced inhibitory action of NG-nitro-L-arginine demonstrates the important role of the arginine/nitric oxide pathway in mediating relaxation of penile smooth muscles necessary for erection.

Hypercontractility and impaired sildenafil relaxations in the BKCachannel deletion model of erectile dysfunction

“…In mice, the NO-producing enzyme NO synthase has been found in the dorsal penile nerve and its branches in the mouse penis (9) as well as in intrinsic nerves of the erectile tissue (14). The majority of NO effects are mediated through the soluble guanylate cyclase (sGC) and its product, cGMP (2,8,16,33). cGMP acts as a modifying agent on ion channels, phosphodiesterases, and protein kinases (19).…”

“…NO effects are mediated through the soluble guanylate cyclase (sGC) and its product, cGMP (2,8,16,33). cGMP acts as a modifying agent on ion channels, phosphodiesterases, and protein kinases (19).…”

“…It affects 30 million men in the United States (5), and its prevalence increases with age and diseases like diabetes and hypertension (4,24,31). Erectile function and a proper penile erection occurs in response to nerve stimulation and the release of nitric oxide (NO) from parasympathetic nonadrenergic-noncholinergic (NANC) nerves as well as from the vascular endothelium (2,13,16,27). In mice, the NO-producing enzyme NO synthase has been found in the dorsal penile nerve and its branches in the mouse penis (9) as well as in intrinsic nerves of the erectile tissue (14).…”

Regulation of the nitric oxide pathway genes by tetrahydrofurandiols: Microarray analysis of MCF-7 human breast cancer cells

“…In the ovary, increases in NO correlate with increases in estrogen, regulates follicular development [36] and ovulation [37]. In the male rabbits, NO induces penile erection [38]. NOS activity localized to the rat penile neurons innervate the corpora cavernosa and eNOS present in the endothelium of penile vasculature act as a physiological mediator of erectile function [39].…”

Discovery of NO in the penis

“…Holmquist et al 15 Figure 3 Relaxation of rabbit corporal smooth muscle by EFS (insert and K) and its inhibition by NG-nitro-L-arginine m; nG-amino-L-arginine n; oxyhemoglobin '; and methylene blue J. (with permission).…”