Neurogenic nitric oxide mediates relaxation of canine corpus cavernosum

PURPOSE: The aim of the present study is to analyze mechanisms underlying neurogenic relaxation of the corpus cavernosum which are believed to participate in penile erection. MATERIALS AND METHODS: Mechanical responses to nerve stimulation by electrical pulses and nicotine were measured in strips of canine corpus cavernosum precontracted with phenylephrine. Cyclic guanosine monophosphate (GMP) contents in the strips were also measured by radioimmunoassay. Immunohistochemistry for nitric oxide synthase (NOS) and vasoactive intestinal polypeptide (VIP) was performed. RESULTS: Transmural electrical stimulation and nicotine produced relaxations in the isolated canine corpus. The neurogenic relaxation was abolished by N omega-nitro-L-arginine, a NOS inhibitor, and the inhibition was reversed by L-arginine. Relaxations induced by nerve stimulation and exogenous nitric oxide (NO) were depressed by oxyhemoglobin and methylene blue. Vasoactive intestinal polypeptide (VIP)-induced relaxations were not influenced by these inhibitors. In the controls strips and those made unresponsive to VIP by its repeated application, the responses to nerve stimulation did not differ. The content of cyclic GMP in the tissue increased in response to nicotine, the effect being abolished by the NO synthase inhibitor. Immunohistochemical study demonstrated neurons containing NOS and VIP. CONCLUSIONS: It appears that the relaxation induced by nerve stimulation is mediated solely by NO liberated from the nerve that activates soluble guanylate cyclase and increases the production of cyclic GMP in smooth muscle, whereas VIP does not play a role in the regulation of muscle tone under the experimental conditions used.     

Nitrergic relaxation of the horse corpus cavernosum. Role of cGMP

A rotatable central composite design is used to evaluate the effects of lubricants and compression force on the physical characteristics of effervescent tablets. Effervescent tablets lubricated with a combination of spray dried L-leucine and polyethylene glycol 6000 are prepared by direct compression and examined. Residual force, crushing strength and disintegration time are considered as response variables and related to the L-leucine and polyethylene glycol concentrations and to the compression force. The calculated models are used to assess the influence of the production factors on tablet properties. As increasing amounts of L-leucine, showing good lubricating properties, reduce the crushing strength and prolong tablet disintegration, the L-leucine concentration is kept at a low level. An optimum tablet formulation contains 2% L-leucine and 3% polyethylene glycol 6000. The tablets have a tensile strength of 0.47 MPa and disintegrate in less than 2 min. Predicted and experimental results are in agreement within a 95% CI.     

Relaxation of corpus cavernosum and raised intracavernous pressure by berberine in rabbit

1. In the present study, we have investigated the effect of berberine in rabbit isolated corpus cavernosum and measured the intracavernous pressure (ICP) change after intracavernosal injection of berberine in rabbit. 2. Berberine alone suppressed the basal tone and induced a concentration (0.1-100 microM)-dependent relaxation in phenylephrine (PE)-precontracted corpus cavernosum. 3. Tetrodotoxin (0.1 and 1 microM) treatment had no significant effect on the berberine-induced relaxation. Phentolamine (1 and 10 microM), propranolol (1 and 3 microM) and atropine (1 and 3 microM) were also without effect. These results suggest that berberine might cause relaxation of the cavernosal strip by direct action on the corpus cavernosum, not by a neuronal effect. Furthermore, muscarinic- and beta-adrenoceptors were not involved. 4. Berberine-induced relaxations were significantly reduced by endothelium removal and by exposure to L-NG-nitro arginine methyl ester (0.1 and 0.3 mM), but not indomethacin (30 microM). 5. In endothelium-deprived corpus cavernosal tissues, berberine-induced relaxations were significantly reduced in high K+ medium (KCl = 60 mM), by charybdotoxin (ChTX) and 4-aminopyridine (4-AP) but not by glibenclamide and apamin. 6. After intracavernous injection of berberine (1, 2, 3 and 5 mg kg(-1)), the ICP rose from 12.7+/-3.6 to 13.2+/-5.4, 25.3+/-6.1, 46.5+/-8.2, and 63.4+/-10.2 mmHg, respectively. The duration of tumescence ranged from 11.5 - 43.7 min. 7. The results show that berberine possesses a relaxant effect on rabbit corpus cavernosal tissues which is attributable to both endothelium-dependent and-independent properties. While the former component is apparently due to the release of NO from sinusoidal endothelium, the endothelium-independent mechanism involved in berberine relaxation is probably linked to ChTX- and 4-AP-sensitive K+ channel activation in the cavernosal vasculature.     

Nitrergic neurotransmission mediates the non-adrenergic non-cholinergic responses in the clitoral corpus cavernosum of the rabbit

The corpus cavernosum is the erectile tissue in the penis and clitoris. Although nitrergic neurotransmission has been characterized in detail in the penile corpus cavernosum, functional studies on the inhibitory non-adrenergic non-cholinergic (NANC) transmission in the clitoral corpus cavernosum have been lacking. Here we demonstrate that electrical field stimulation (EFS) induces NANC relaxation responses in the clitoral corpus cavernosum of the rabbit. These responses were inhibited by NG-nitro-L-arginine methylester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) or tetrodotoxin. The inhibitory effect of L-NAME was partially reversed by L-arginine but not by D-arginine. EFS-induced relaxations were enhanced by an inhibitor of type V cyclic GMP phosphodiesterase, zaprinast. These results suggest that nitrergic neurotransmission is responsible for the NANC relaxation responses in the clitoral corpus cavernosum of the rabbit.     

Metabolic responses of rabbit corpus cavernosum tissue to various forms of stimulation

The present study was designed to investigate the effect of various forms of stimulation on the levels of high energy phosphates (ATP + CP) in the rabbit corpora cavernosa. Prestimulation with the alpha agonist phenylephrine (200 microM) for five minutes caused a significant decrease in both ATP and Creatine phosphate (CP) when compared with control tissue. Field stimulation (64 Hz) of the precontracted tissue induced an immediate decrease in tension by approximately 50%. The level of ATP + CP after field stimulated-relaxation was not significantly different from that from the initial prestimulation. Field stimulation (FS) from basal tone (2 g) caused a contraction and a significant decrease in both ATP and CP. Phentolamine (10 microM) (alpha-adrenergic antagonist) induced a significant decrease in the 2 g basal tension and a significant increase in the intracellular concentrations of both ATP and CP from that of control levels. In summary, the contractile response to both neuronal and pharmacologic stimulation was similar to that of other smooth muscle, producing a decrease in high energy phosphates. Field stimulated relaxation did not change the level of high energy phosphates from that of prestimulated levels. Finally, our data indicates that in the presence of the alpha blocker phentolamine (10 microM), high energy phosphate levels (ATP + CP) increase significantly. This indicates that in the corpus cavernosum, there is significant basal tone that is linked to significant tonic alpha receptor stimulation and is maintained by a net consumption of ATP.     

Autoradiographic localization of nitric oxide synthase binding sites in normal and diabetic rat corpus cavernosum

OBJECTIVES: To investigate density and distribution of nitric oxide synthase (NOS) binding sites in rat cavernosal tissue, and to assess any changes brought about by the onset of diabetes mellitus. METHODS: Hyperglycaemic non-ketonuric diabetes mellitus was induced in 5 rats using streptozotocin. The penises were excised from these rats 2 months after the administration of streptozotocin and stored at -70 degrees C. Longitudinal serial sections (6 microns) were cut in a cryostat and thaw mounted onto gelantinized microscope slides. Low- and high-resolution autoradiography was performed using a radioligand for NOS. Densitometric analysis was performed on the autoradiographs and the results compared with those obtained from 5 age-matched no-diabetic rats. RESULTS: NOS binding was primarily localized to the endothelium lining the cavernosal lacunar spaces. Significantly increased binding of NOS was seen in the diabetic cavernosal tissue 2 months after induction of diabetes mellitus. CONCLUSIONS: NOS binding is present on the endothelium of the rat corpus cavernosum and is increased in diabetic rats 2 months after streptozotocin administration. This increase in NOS binding may be part of the endothelial dysfunction which is reported in the corpus cavernosum of diabetic patients or rats.     

Evidence that different mechanisms underlie smooth muscle relaxation to nitric oxide and nitric oxide donors in the rabbit isolated carotid artery

1. The endothelium-dependent relaxants acetylcholine (ACh; 0.03-10 microM) and A23187 (0.03-10 microM), and nitric oxide (NO), applied either as authentic NO (0.01-10 microM) or as the NO donors 3-morpholino-sydnonimine (SIN-1; 0.1-10 microM) and S-nitroso-N-acetylpenicillamine (SNAP; 0.1-10 microM), each evoked concentration-dependent relaxation in phenylephrine stimulated (1-3 microM; mean contraction and depolarization, 45.8+/-5.3 mV and 31.5+/-3.3 mN; n=10) segments of rabbit isolated carotid artery. In each case, relaxation closely correlated with repolarization of the smooth muscle membrane potential and stimulated a maximal reversal of around 95% and 98% of the phenylephrine-induced depolarization and contraction, respectively. 2. In tissues stimulated with 30 mM KCl rather than phenylephrine, smooth muscle hyperpolarization and relaxation to ACh, A23187, authentic NO and the NO donors were dissociated. Whereas the hyperpolarization was reduced by 75-80% to around a total of 10 mV, relaxation was only inhibited by 35% (n=4-7 in each case; P<0.01). The responses which persisted to ACh and A23187 in the presence of 30 mM KCl were abolished by either the NO synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME; 100 microM) or the inhibitor of soluble guanylyl cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 microM; 10 min; n=4 in each case; P<0.01). 3. Exposure to ODQ significantly attenuated both repolarization and relaxation to ACh, A23187 and authentic NO, reducing the maximum changes in both membrane potential and tension to each relaxant to around 60% of control values (n=4 in each case; P<0.01). In contrast, ODQ almost completely inhibited repolarization and relaxation to SIN-1 and SNAP, reducing the maximum responses to around 8% in each case (n=3-5; P<0.01). 4. The potassium channel blockers glibenclamide (10 microM), iberiotoxin (100 nM) and apamin (50 nM), alone or in combination, had no significant effect on relaxation to ACh, A23187, authentic NO, or the NO donors SIN-1 and SNAP (n=4 in each case; P>0.05). Charybdotoxin (ChTX; 50 nM) almost abolished repolarization to ACh (n=4; P<0.01) and inhibited the maximum relaxation to ACh, A23187 and authentic NO each by 30% (n=4-8; P<0.01). Application of ODQ (10 microM; 10 min) abolished the ChTX-insensitive responses to ACh, A23187 and authentic NO (n=4 in each case; P<0.01 5. When the concentration of phenylephrine was reduced (to 0.3-0.5 microM) to ensure the level of smooth muscle contraction was the same as in the absence of potassium channel blocker, ChTX had no effect on the subsequent relaxation to SIN-1 (n=4; P>0.05). However, in the presence of tone induced by 1-3 microM phenylephrine (51.2+/-3.3 mN; n=4), ChTX significantly reduced relaxation to SIN-1 by nearly 50% (maximum relaxation 53.2+/-6.3%, n=4; P<0.01). 6. These data indicate that NO-evoked relaxation of the rabbit isolated carotid artery can be mediated by three distinct mechanisms: (a) a cyclic GMP-dependent, voltage-independent pathway, (b) cyclic GMP-mediated smooth muscle repolarization and (c) cyclic GMP-independent, ChTX-sensitive smooth muscle repolarization. Relaxation and repolarization to both authentic and endothelium-derived NO in this large conduit artery appear to be mediated by parallel cyclic GMP-dependent and -independent pathways. In contrast, relaxation to the NO-donors SIN-1 and SNAP appears to be mediated entirely via cyclic GMP-dependent mechanisms.     

Isolation and partial characterization of a polypeptide from Phoneutria nigriventer spider venom that relaxes rabbit corpus cavernosum in vitro

The venom of the Brazilian spider Phoneutria nigriventer was fractionated using a C18 microBondapack reverse-phase high-performance liquid chromatography column. The resulting fractions were assayed in the rabbit perfused corpus cavernosum tissue to identify those fractions responsible for the corpus cavernosum relaxation. Two fractions (A and B) with retention times of 18.1 and 36.7 min, respectively, induced relaxation of corpus cavernosum strips. Fraction A was selected for further biochemical characterization. Repurification of this fraction revealed the presence of a polypeptide (named PNV4) which migrates in sodium dodecyl sulphate-polyacrylamide gel electrophoresis as a single band consistent with a mol. wt close to 16,600. The amino acid composition of PNV4 showed the presence of 147 residues, a high content of Cys and a calculated mol. wt of 17,213 + Trp. The N-terminal amino acid sequence of PNV4 determined for its first 48 residues was AELTSCFPVGHECDGDASNCNCCGDDVYCGCGWGRWNCKCKVADQSYA.     

Effects of castration on adrenergic, cholinergic and nonadrenergic, noncholinergic responses of isolated corpus cavernosum from rabbit

OBJECTIVE: To investigate the effects of castration and testosterone on the constricting effect of phenylephrine and endothelium-dependent and -independent relaxing effects of different agonists in the corpus cavernosum of male rabbits. MATERIALS AND METHODS: Twenty rabbits were castrated and 10 received testosterone replacement for 1 month after castration; 10 further rabbits underwent a sham operation and acted as controls. One month after operation the rabbits were killed and their penises excised. Strips of corpus cavernosum were used for isometric tension measurements in organ chambers; concentration-response relationships for phenylephrine, carbachol, adenosine and sodium nitroprusside were obtained by adding the reagent cumulatively to the bath. RESULTS: The phenylephrine-induced contractions were markedly lower, with no change in the pD2 values (i.e. the negative logarithm of the concentration for half-maximal response), in cavernosal strips obtained from castrated rabbits than in those from controls. Endothelium-dependent relaxation elicited by carbachol increased in the castrated group but the relaxation induced by sodium nitroprusside did not change and those elicited by adenosine were strongly depressed when compared with controls. There were no significant changes in the pD2 values of agonist-induced relaxation responses in all groups. The relaxation elicited by electrical-field stimulation at lower frequencies increased in strips from castrated rabbits but at higher frequencies were unchanged when compared with controls. Castration-induced changes in the relaxation response of cavernosal strips were significantly restored by in vivo testosterone replacement but those induced by phenylephrine were not. CONCLUSION: The lack of testosterone has an effect on the reactivity of the corpus cavernosum, indicating that testosterone has an important role in erectile function by a pre- or post-synaptic action on the corpus cavernosum.     

Role of nitric oxide and nitric oxide-independent relaxing factor in contraction and relaxation of rabbit blood vessels

The objective of the present study was to estimate the maximal velocity (Vmax) and Michaelis affinity constant (Km) for the oxidation of pyrene to 1-hydroxypyrene using rat liver post-mitochondrial fractions. The approach involved the determination of the concentrations of 1-hydroxypyrene formed during 5 min incubations of pyrene (initial concentrations: 0.0025-0.5 microM), and correcting for the rate of 1-hydroxypyrene disappearance (2.16 x 10(-5) per (mg protein/l)/min) during the incubation period. The Vmax and Km for pyrene metabolism in the rat corresponded to 0.0577 +/- 0.0108 micromol/min per g liver and 27.73 +/- 13.54 microM, respectively. The intrinsic clearance (CL(int)) of pyrene in the rat estimated in the present study (0.041-0.111 l/min per kg) was within the range of the previously reported CL(int) in humans (0.037-0.125 l/min per kg). The results of this study suggest that CL(int) of pyrene in humans can be predicted from such data obtained in the rat.     

Lovastatin maintains nitric oxide--but not EDHF-mediated endothelium-dependent relaxation in the hypercholesterolemic rabbit carotid artery

The endothelium contributes to the regulation of vascular tone by producing nitric oxide (NO) and the endothelium-derived hyperpolarising factor (EDHF). In hypercholesterolemia, endothelium-dependent relaxation is impaired but can be restored by treatment with lovastatin (LOVAS). We investigated the effects of LOVAS on NO and EDHF-mediated relaxation. Rabbits were fed 1% cholesterol diet for 4 weeks and 0.5%) cholesterol for the following 12 weeks (CHOL-group). The LOVAS group additionally received 10 mg of lovastatin over the last 12-week period. Experiments were performed in carotid artery rings. Relaxant responses to acetylcholine (ACh) were recorded in the presence of indomethacin. Nitro-L-arginine (NOARG, 100 microM) and potassium chloride (KCl, 35 mM) were used to differentiate between NO- and EDHF-mediated relaxations. Cholesterol impaired ACh-induced relaxations and this effect was prevented by LOVAS (control 100+/-1%, CHOL 81+/-6%, LOVAS 98+/-1%). In the presence of NOARG, relaxations to ACh were not different between the LOVAS and CHOL groups (control 78+/-4%, CHOL 64+/-6%, LOVAS 64+/-5%). When KCl was used, ACh-induced relaxations were similar in the LOVAS and control group (control 75+/-5%, CHOL 49+/-6%, LOVAS 76+/-2%). In arteries treated with NOARG and KCl together, no relaxations were observed. Relaxations of arteries from the control group were not affected by 18 h preincubation with lovastatin (10 microM). Lovastatin selectively maintains nitric oxide-mediated endothelium-dependent relaxation in hypercholesterolemic rabbit carotid arteries.     

Patterns of messenger RNA expression for alpha1-adrenoceptor subtypes in human corpus cavernosum

PURPOSE: The present study evaluated the expression of alpha1-adrenoceptor subtypes in human corpus cavernosum. MATERIALS AND METHODS: The mRNA encoding alpha1a, alpha1b and alpha1d subtypes were assessed by RNA-directed complementary cDNA synthesis followed by Taq DNA amplification. The level of alpha1 mRNA was calculated in arbitrary optical density units and normalized with respect to the length of the respective cDNA fragments. RESULTS: We found that alpha1a, alpha1b and alpha1d adrenoceptor subtypes are expressed in human corpus cavernosum, with a predominant expression of the alpha1a subtype. CONCLUSION: These results suggest that alpha1a-adrenoceptor subtype is important and that understanding the biochemical and functional characteristics of this subtype may lead to the development of specific antagonists in the treatment of impotence.     

Evidence that additional mechanisms to cyclic GMP mediate the decrease in intracellular calcium and relaxation of rabbit aortic smooth muscle to nitric oxide

1. The role of cyclic GMP in the ability of nitric oxide (NO) to decrease intracellular free calcium concentration [Ca2+]i and divalent cation influx was studied in rabbit aortic smooth muscle cells in primary culture. In cells stimulated with angiotensin II (AII, 10(-1) M), NO (10(-10) - 10(-6) M) increased cyclic GMP levels measured by radioimmunoassay and decreased [Ca2+]i and cation influx as indicated by fura-2 fluorimetry. 2. Zaprinast (10(-4) M), increased NO-stimulated levels of cyclic GMP by 3-20 fold. Although the phosphodiesterase inhibitor lowered the level of [Ca2+]i reached after administration of NO, the initial decreases in [Ca2+]i initiated by NO were not significantly different in magnitude or duration from those that occurred in the absence of zaprinast. 3. The guanylyl cyclase inhibitor, H-(1,2,4) oxadiazolo(4,3-a) quinoxallin-1-one (ODQ, 10(-5) M), blocked cyclic GMP accumulation and activation of protein kinase G, as measured by back phosphorylation of the inositol trisphosphate receptor. ODQ and Rp-8-Br-cyclic GMPS, a protein kinase G inhibitor, decreased the effects of NO, 10(-10) - 10(-8) M, but the decrease in [Ca2+]i or cation influx caused by higher concentrations of NO (10(-7) - 10(-6) M) were unaffected. Relaxation of intact rabbit aorta rings to NO (10(-7) - 10(-5) M) also persisted in the presence of ODQ without a significant increase in cyclic GMP. Rp-8-Br-cyclic GMPS blocked the decreases in cation influx caused by a cell permeable cyclic GMP analog, but ODQ and/or the protein kinase G inhibitor had no significant effect on the decrease caused by NO. 4. Although inhibitors of cyclic GMP, protein kinase G and phosphodiesterase can be shown to affect the decrease in [Ca2+]i and cation influx via protein kinase G, these studies indicate that when these mechanisms are blocked, cyclic GMP-independent mechanisms also contribute significantly to the decrease in [Ca2+]i and smooth muscle relaxation to NO.     

Role of nitric oxide and vasoactive intestinal polypeptide in vagally mediated relaxation of the gastric corpus in the anaesthetized ferret

We have examined the role of protein kinase C (PKC) in the stimulation of protein synthesis by insulin using two complementary approaches. In the first, fibroblasts were pretreated with phorbol esters to down-regulate PKC. In these cells, the effects of insulin and of phorbol esters on protein synthesis were completely abolished, although serum still elicited an effect approaching that seen in control cells. Secondly, we used newly developed inhibitors of PKC which, again, blocked the effects of insulin and phorbol esters without greatly reducing the response to serum. Thus PKC apparently plays an important role in the stimulation of translation by insulin.     

Penile fracture: MRI demonstration of a urethral tear associated with a rupture of the corpus cavernosum

We report a case of traumatic urethral tear associated with a rupture of the corpus cavernosum, demonstrated on MRI. We discuss the potential role of a non-invasive preoperative assessment by MRI.     

Ovarian regulation of postcoital gonadotropin release in the rabbit: reexamination of a functional role for 20 alphadihydroprogesterone

In the rabbit, it has proposed that an ovarian progestin, 20 alpha-dihydroprogesterone (20alphaP), released at mating, is essential for a normal postcoital LH surge. However, we measured plasma levels of LH and 20alphaP after mating in rabbits and observed that the frequency, magnitude and time-course of changes in circulating levels of 20alphaP seemed inappropiate to account for the rapid and major surge of LH secretion. This prompted us to re-evalute the role of the ovary in regulating postcoital LH secretion. In chronically ovariectomized (greater than 30 days) does pretreated with estrogen, mating induced a normal LH surge in only 1 of 10 animals, indicating that an ovarian product in addition to estrogen is required for a normal postcoital LH surge. However, when 20alphaP was injected soon after mating in chronically ovariectomized does pretreated with estrogen, only 2 of 9 displayed normal LH surges; this proportion is not different from that (1/10) observed with estrogen treatment alone. To demonstrate that the estrogen treatment, which produced supraphysiologic plasma estradiol levels, did not itself block LH release, 6 intact anestrus females were treated with the same estrogen regimen. Estrus was induced in 5 and each displayed a large post-coital LH surge and ovulated. As a final test of the 20alphaP hypothesis, 5 spontaneously estrous does were ovariectomized within 15 min post coitum to abolish acute increases in circulating ovarian hormones. Three animals released LH in amounts and temporal pattern indistinguishable from intact estrous does. A fourth released smaller amounts of LH. Two of 4 sham-operated does also had normal LH surges. These findings indicate that ovarian hormones are required before mating to support the capacity of the LH secretory mechanism to respond to coitus. Chronic alteration in the hormonal milieu by ovariectomy appears to produce a change in the hypothalamo-hypophysial complex that is not reversed by estrogen, alone. More importantly, these results demonstrate clearly that neither 20alphaP nor any other ovarian hormone is required post coitum, at least after 15 min, for normal LH release.     

Quantitative analysis of smooth muscle fibers in corpus cavernosum of human fetuses

PURPOSE: Quantify objectively the normative distribution and the percentage of smooth muscle fibers in the corpus cavernosum of human fetuses with 24 weeks post-conception (WPC) of gestational age. MATERIAL AND METHODS: We studied 7 penises taken from 7 fresh human fetuses. We analyzed 5 randomized sections from each penis and in every section we analyzed 3 fields, totaling 15 fields per penis and 105 fields for the final results. Immunohistological staining for the smooth muscle fibers was used to accentuate the differences between the intracavernous structures (smooth muscle fibers and collagen fibers). The fields studied were digitized with a final magnification of 450X and a computerized analysis of the smooth muscle fibers was performed with image analyzer software. The percentage of smooth muscle fibers per standard square area was estimated and the mean value was used for each penis. RESULTS: The distribution of smooth muscle fibers in the corpus cavernosum of human fetuses with 24 WPC of gestational age ranged from 17.52% to 27.76% of the total area. The mean value was 22.72% and the standard deviation was 3.56. CONCLUSIONS: Our results show that the percentage of smooth muscle cells in corpus cavernosum of human fetuses with 24 WPC of gestational age is significantly smaller when compared with the data available for adult cadavers.     

The expression of functional postsynaptic alpha2-adrenoceptors in the corpus cavernosum smooth muscle

1. The purpose of this study was to determine if corpus cavernosum smooth muscle expresses functional postsynaptic alpha2-adrenoceptors (AR). 2. The alpha2-adrenoceptor agonist UK 14,304 elicited concentration-dependent contractions in rabbit corpus cavernosum smooth muscle (CCSM). The half-maximal response occurred at 0.32+/-0.03 microM and the maximum contraction at 10 microM UK 14,304. 3. Pretreatment of CCSM strips with selective alpha2-adrenoceptor antagonists, rauwolscine and RS-15385, produced rightward shifts in the dose-response curves to UK 14,304 (pA2 values 7.1 and 8.5, respectively). In contrast, these antagonists did not alter contraction induced by the alpha1-adrenoceptor agonist phenylephrine (PE) or oxymetazoline. UK 14,304-induced contractions were also inhibited by prazosin (pA2 = 9.08). 4. UK 14,304-induced contractions, unlike those to PE, were highly dependent on the presence of extracellular Ca2+. 5. [3H]-rauwolscine bound to CCSM membranes with high affinity (Kd = 1.5 nM). [3H]-rauwolscine binding was displaced by unlabelled rauwolscine, RS-15385, UK 14,304 and prazosin, but not by PE. 6. UK 14,304 inhibited forskolin and prostaglandin E1 (PGE1)-induced increases in intracellular cyclic AMP concentration in primary cultures of rabbit CCSM cells. 7. These results demonstrate that CCSM expresses Gi-coupled postsynaptic alpha2-adrenoceptors, and activation of these receptors causes contraction of trabecular smooth muscle.