Nitric oxide release in penile corpora cavernosa in a rat model of erection

Abstract

1. Nitric oxide (NO) levels were measured in the corpus cavernosum of urethane-anaesthetized rats by using differential normal pulse voltammetry with carbon fibre microelectrodes coated with a polymeric porphyrin and a cation exchanger (Nafion). A NO oxidation peak could be recorded at 650 mV vs. a Ag-AgCl reference electrode every 100 s. 2. This NO signal was greatly decreased by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), given by local and systemic routes, and enhanced by the NO precursor L-arginine. Treatment with L-arginine reversed the effect of L-NAME on the NO peak. 3. Both the NO signal and the intracavernosal pressure (ICP) were increased by electrical stimulation of cavernosal nerves (ESCN). However, the rise in the NO levels long outlived the rapid return to baseline of the ICP values at the end of nerve stimulation. 4. The ICP and the NO responses to ESCN were suppressed by local and systemic injections of L-NAME. Subsequent treatment with L-arginine of L-NAME-treated animals restored the NO signal to basal levels and the NO response to ESCN. The ICP response to ESCN was restored only in part by L-arginine. 5. The observed temporal dissociation between the NO and ICP responses could be accounted for by several factors, including the buffering of NO by the blood filling the cavernosal spaces during erection. 6. These findings indicate that an increased production of NO in the corpora cavernosa is necessary but not sufficient for maintaining penile erection and suggest a complex modulation of the NO-cGMP-cavernosal smooth muscle relaxation cascade.

Figure 1. Voltammograms recorded in the corpus cavernosum of two urethane-anaesthetized rats before (BL) and after infusion of different NO solutions in the vicinity of the electrode (A) and electrical stimulation of the cavernous nerve (ESCN) (B)

Traces 1-3 in B are consecutive recordings in the same animal, at 100 s intervals, following ESCN. It usually takes 2-3 scans after nerve stimulation for the NO signal to reach maximal values (in this example, in the second scan, trace 2); it then decays slowly (trace 3).

Figure 2. Effects of intracavernosal (ICI) or intravenous (SYS) injections (dotted lines) of the NO precursor L-arginine and the NOS inhibitor L-NAME, alone or in combination, on the size of the NO signal recorded in the corpus cavernosum

Data are means ±s.e.m.; 7-11 animals per group; * P < 0.05 vs. baseline levels. The doses used were as follows: ICI, a 60 μl infusion of 40 μM L-arginine or 30 μM L-NAME; SYS, L-arginine, 25 mg kg⁻¹; SYS, L-NAME, 3 mg kg⁻¹. The initial drop in the voltammetric signal following the ICI of vehicle denotes a transient dilution effect.

Figure 3. Effects of cavernous nerve stimulation (ESCN)

A, changes in the NO electrochemical signals recorded in the corpus cavernosum. Data are means ±s.e.m.; n = 12

Figure 4. Effects of pretreatments with L-arginine or L-NAME on the response of the NO voltammetric signal to ESCN

Data are means ±s.e.m.; 6-9 animals per group; *P < 0.05 vs. baseline preinjection levels. See legends to Figs 2 and 3 for further details.

Figure 5. Effects of L-arginine on the NO signal recorded before and after ESCN in L-NAME pretreated rats

Data are means ±s.e.m.; 5 animals per group; *P < 0.05 vs. baseline preinjection levels. See legends to Figs 2 and 3 for further details.

Figure 6. Size of the NO voltametric signal recorded in PBS or rat arterial blood immediately after adding NO to a final concentration of either 2 or 10 μmol l⁻¹

Data are means ±s.e.m. of 3 electrodes; * P < 0.01 vs. PBS. Note the change in scale.