Enhancement of apomorphine-induced penile erection in the rat by a selective alpha(1D)-adrenoceptor antagonist

Abstract

1. Effects of A-322312 (alpha(1B)-adrenoceptor (AR) antagonist), A-119637 (alpha(1D)-AR antagonist), prazosin (non-selective alpha(1)-AR antagonist), and yohimbine (alpha(2)-AR antagonist) were studied in rat corpus cavernosum (CC) and cavernous artery (Acc) preparations. Effects of intracavernous (i.c.) or intraperitoneal (i.p.) administration of alpha(1)-AR antagonists on apomorphine-induced erections were investigated. 2. A-119637 attenuated electrically induced contractions in isolated CC (-logIC(50); 8.12+/-0.15), and relaxed noradrenaline (NA)-contracted preparations by more than 90% at 10(-7) M. At the same concentration, the -logEC(50) value for NA in Acc was altered from 6.79+/-0.07 to 4.86+/-0.13. In the CC and Acc, prazosin similarly inhibited contractile responses. 3. Inhibitory effects of A-322312 (10(-7) M) in electrically activated CC were 32.3+/-5.1%, whereas no effect on concentration-response curves for NA was observed in the Acc. Yohimbine (10(-8) M and 10(-7) M), enhanced electrically-induced contractions in isolated CC by 20 to 50%. At 10(-6) M, inhibitory effects of yohimbine were obtained. 4. A-119637 (0.3 micromol kg(-1), i.p.) tripled the number of erections, and produced a 6 fold increase in the duration of apomorphine-induced erectile responses. A-322312, prazosin, or yohimbine did not enhance erections induced by apomorphine. None of the alpha(1)-AR antagonists significantly increased ICP upon i.c. administration. Decreases in blood pressure were seen with A-119637 and prazosin. 5. The present findings show that there is a functional predominance of the alpha(1D)-AR subtype in the rat erectile tissue, and that blockade of this receptor facilitates rat penile erection induced by a suboptimal dose of apomorphine.

Figure 1

(A) Effects of α-adrenoceptor antagonists or vehicle (10⁻¹⁰ M – 10⁻⁶ M; N=7) on contractions induced by electrical field stimulation (18 Hz, 20 V), or (B) by noradrenaline (NA; 3×10⁻⁶ M, N=6) in the rat isolated corpus cavernosum. Effects are expressed as per cent enhancement/inhibition/relaxation of contraction, and values are given as mean±standard error of the mean.

Figure 2

(A) Effects of prazosin (10⁻⁹ – 10⁻⁷ M), or (B) A-119637 (10⁻⁹ – 10⁻⁷ M), on contractions induced by noradrenaline (NA; 10⁻⁹ – 10⁻⁴ M, N=5) in the rat isolated cavernous artery (Acc). NA-induced contractile effects are expressed as per cent of K⁺ (124 mM) contraction, and values are given as mean±standard error of the mean.

Figure 3

Number and duration of erectile responses induced by intraperitoneal administration of α₁-adrenoceptor antagonists (0.3 μmol kg⁻¹) or vehicle (N=6 each) during submaximal stimulation with apomorphine (25 μg kg⁻¹, s.c.). The results are presented as mean values±standard error of the mean. ^*P<0.05.

Figure 4

A tracing showing intracavernous pressure changes by subcutaneous apomorphine (25 μg kg⁻¹) in rats pretreated with intraperitoneal α_1D-adrenoceptor antagonists (A-119637, 0.3 μmol kg⁻¹) or vehicle.

Figure 5

Area under the curve of erectile responses induced by intraperitoneal or intracavernous administration of α₁-adrenoceptor antagonists or vehicle during submaximal stimulation with apomorphine (25 μg kg⁻¹, s.c.). The results are presented as mean values±standard error of the mean. ^*P<0.05.

Figure 6

Number and duration of erectile responses induced by intracaverrnous administration of α₁-adrenoceptor antagonists (0.3 μmol kg⁻¹, N=6 each) or vehicle (N=7) during submaximal stimulation with apomorphine (25 μg kg⁻¹, s.c.). The results are presented as mean values±standard error of the mean. ^*P<0.05.