Effect of aldosterone on isolated human penile corpus cavernosum tissue

OBJECTIVE

To clarify the physiological effects of aldosterone on human penile corpus cavernosum (hPCC) tissue, as aldosterone has a wider physiological action than just the maintenance of electrolyte balance, and there are mineralocorticoid receptors, i.e. aldosterone receptors, in hPCC tissue.

MATERIALS AND METHODS

Specimens of hPCC were obtained from 10 patients (mean age 38 years, range 21–75), with informed consent and approval by the local ethics committee. One patient had a penectomy because of penile cancer, and nine had a penile biopsy because of erectile dysfunction. Patients with diabetes mellitus, hypertension or ischaemic heart disease were excluded. In a pharmacological study we evaluated the effect of aldosterone on the isolated hPCC tissues.

RESULTS

Aldosterone caused no significant change in resting tension and did not affect the nitric oxide‐dependent relaxation reaction. However, the dose–response curve of noradrenaline was shifted to the left when the strip preparation was treated with aldosterone (1 × 10^?5m ) for 20 min before administering noradrenaline. Moreover, the shift to the left was completely blocked when spironolactone (anti‐aldosterone agent) was added as a pre‐treatment. Pre‐treatment with aldosterone also significantly extended the mean (sem ) time required to reach 50% relaxation of a noradrenaline‐induced contraction, of 9.3 (1.5) min, vs the control, of 5.2 (1.0) min (P = 0.002).

CONCLUSION

Aldosterone has no direct contractile action or a relaxant action on human penile cavernous tissue, but acts to significantly enhance the noradrenaline‐induced contraction. The effect on the noradrenaline‐induced contraction is probably caused by aldosterone enhancing the affinity of the α‐receptors for noradrenaline in hPCC. We suggest that aldosterone acts to enhance contraction of hPCC tissue, and is one of the restraining factors for human penile erection.     

Regulation of adrenergic activity in penile corpus cavernosum

The regulation of adrenergic activity in the penis was investigated by studying human and rabbit corpus cavernosum strips in organ chambers and measuring the release of norepinephrine from adrenergic nerve terminals. Electrical field stimulation of corporal strips caused frequency-dependent contractions which were potentiated by cocaine and attenuated by the alpha 1 adrenoceptor antagonist prazosin (10(-7) M), but not by the alpha 2 adrenoceptor antagonist rauwolscine (10(-7) M). Norepinephrine caused concentration-dependent contractions of corporal strips, which were attenuated by prazosin and rauwolscine. Acetylcholine and physostigmine attenuated adrenergic nerve mediated contractions and also significantly reduced electrically-induced norepinephrine release. These effects were reversed by atropine. Atropine alone enhanced electrically-induced norepinephrine release. Rauwolscine inconsistently enhanced adrenergic nerve mediated contractions but augmented norepinephrine release caused by electrical stimulation. The alpha 2 adrenoceptor agonist clonidine inhibited electrically-induced norepinephrine release. Vasoactive intestinal polypeptide (VIP) attenuated adrenergically-mediated contractions, but had no effect on electrically-induced release of norepinephrine. It is concluded that: 1) contraction of corporal smooth muscle is mediated by postjunctional alpha 1 adrenoceptors; 2) adrenergic activity is modulated by prejunctional alpha 2 adrenoceptors and cholinergic nerves via prejunctional muscarinic receptors; and 3) the putative nonadrenergic noncholinergic neurotransmitter, VIP, has no apparent role in the regulation of adrenergic nerves.     

Comparison of the relaxant effects of alfuzosin,phentolamine and sildenafil on rabbit isolated corpus cavernosum

OBJECTIVE: To compare the direct relaxant effects of alfuzosin, phentolamine and sildenafil in rabbit isolated corpus cavernosum (CC) pre-contracted with phenylephrine or KCl. MATERIALS AND METHODS: Penile erectile tissue was obtained from male New Zealand White rabbits (22-26 weeks old). The CC was cut into longitudinal strips and mounted under 2 g resting tension in 5-mL jacketed organ baths containing a modified Krebs solution bubbled with 95% O2, 5% CO2 and maintained at 37 degrees C. Tissue strips were pre-contracted by 60 mmol/L KCl or 10 micro mol/L phenylephrine. After obtaining a stable plateau of contractions, test compounds were added to the organ bath. The relaxant potencies were expressed as the percentage of inhibition of the plateau of contraction induced by 10 micro mol/L phenylephrine. RESULTS: Alfuzosin showed a concentration-dependent relaxing effect on rabbit CC pre-contracted by 10 micro mol/L phenylephrine, with a mean (sd) pIC50 of 7.64 (0.06). The relaxant effect was unaffected by pre-incubation with 100 micro mol/L Nomega-nitro-l-arginine methyl ester (L-NAME). Phentolamine had a potency similar to alfuzosin, with a pIC50 of 7.44 (0.08). Both alfuzosin and phentolamine were completely ineffective on the plateau of contraction induced by 60 mmol/L KCl. In contrast to alfuzosin, sildenafil was equipotent in relaxing the rabbit CC against each contractile agent, with pIC50 values of 7.25 (0.09) and 7.23 (0.22) with 10 micro mol/L phenylephrine and 60 mmol/L KCl, respectively. The relaxant response to sildenafil was partly blocked by pretreatment with 100 micro mol/L L-NAME, with pIC50 values of 7.94 (0.09) and 6.63 (0.32) without and with L-NAME, respectively. Sildenafil, incubated for 45 min at 10 micro mol/L, had no relaxant effect on the resting tension of the preparation or on the concentration-response curve to phenylephrine. CONCLUSIONS: The direct relaxant effect of alfuzosin is mediated through alpha1-adrenoceptor blockade. The relaxations induced by phentolamine and alfuzosin are independent of nitric oxide, whereas those induced by sildenafil are, at least partly, sensitive to L-NAME and a selective soluble guanylate cyclase inhibitor, indicating the involvement of nitric oxide and soluble guanylate cyclase. Alfuzosin and phentolamine effectively counteract alpha1-adrenoceptor-mediated contractions of rabbit CC. If valid for human CC, such an effect may contribute to an improved erectile function in patients treated for benign prostatic hyperplasia.     

Effect of avanafil on rat and human corpus cavernosum

We compared the activity of a new phosphodiesterase‐5 inhibitor (PDE5i) avanafil with sildenafil and tadalafil in human and rat corpus cavernosum (CC) tissues. The effect of avanafil with several inhibitors and electrical field stimulation (EFS) was evaluated on CC after pre‐contraction with phenylephrine. With the PDE5i, sildenafil and tadalafil, concentration–response curves were obtained and cyclic guanosine monophosphate (cGMP) levels were measured in tissues. Avanafil induced relaxation with maximum response of 74 ± 5% in human CC. This response was attenuated by NOS inhibitor and soluble guanylate cyclase (sGC) inhibitor. Avanafil potentiated relaxation responses to acetylcholine and EFS in human CC and enhanced SNP‐induced relaxation and showed 3‐fold increase in cGMP levels. When compared with sildenafil, avanafil and tadalafil were effective at lower concentrations in human CC. In addition, Sprague–Dawley rats underwent in vivo intracavernosal pressure (ICP) and mean arterial pressure (MAP) measurements. Avanafil increased ICP/MAP that was enhanced by SNP and cavernous nerve (CN) stimulation in rat CC tissues. Also avanafil showed maximum relaxation response of 83 ± 7% in rat CC with 3‐fold increase in cGMP concentration. Taken together, these results of our in vivo and in vitro studies in human and rat suggest that avanafil promotes the CC relaxation and penile erection via NO‐cGMP pathway.     

5-HT4 receptors in isolated human corpus cavernosum?

The novel serotonin subtype-4 (5-HT4) receptor agonist, SC53116 (SC), produced a limited relaxation of noradrenaline (NA) pre-contracted human corpus cavernosum (CC) smooth muscle in vitro. This effect was not significantly attenuated by the 5-HT4 antagonist SDZ250557 (SDZ). In the presence of (+/-) pindolol (1 microM) and methysergide (1 microM), employed to mask 5-HT1 and beta-adrenergic, and 5-HT2 receptors respectively, SC failed to relax NA pre-contracted CC strips to a greater extent than saline. Functional cAMP dependent relaxation pathways were demonstrated by a significant reduction in NA induced tone by prostaglandin E1 (PGE1) and isopropylnoradrenaline (IPNA), the action of the latter compound was effectively eliminated in the presence of (+/-) pindolol. Relaxation of NA induced tone caused by the nitric oxide donor nitro-glycerine (NTG) was significant and similar in the absence and presence of the 5-HT and beta-adrenergic antagonists. The results of this present study indicate that human corporal smooth muscle does not contain 5-HT4 receptors and that, although compounds like SC act to relax non-vascular smooth muscle via cAMP dependent mechanisms, 5-HT4 receptor agonists may be expected to be of limited utility in triggering cAMP dependent relaxation responses in human CC.     

Regulation of pre-synaptic alpha adrenergic activity in the corpus cavernosum

The neurotransmitters and vasoactive substances regulating tone in the smooth muscle of the penile arteries/arterioles and the trabeculae of the corpora cavernosa are critical mediators of the state of penile erection. Contemporary research reveals a coordinated, intricate interplay between the pathways of vasorelaxation and vasoconstriction representing a most efficient physiological mechanism to initiate and maintain penile erection. This paper will focus on the role of the adrenergic constrictor pathways in penile erection and, more specifically, on the pre-junctional adrenergic mechanisms that regulate smooth muscle constriction. All neurogenic constrictor responses are related to the release of norepinephrine from adrenergic nerves that act on post-junctional alpha-1 and pre-junctional and post-junctional alpha-2 receptor subtypes. Based on the current state of knowledge, there are at least three pre-junctional mechanisms regulating penile smooth muscle tone. First, norepinephrine release from the adrenergic nerves binds to the pre-junctional alpha-2 adrenoceptor on the adrenergic nerves and negatively regulates norepinephrine release. Blockade of this reaction by selective alpha-2 receptor antagonists (e.g. yohimbine or delequamine) will enhance norepinephrine release. Second, norepinephrine release from the adrenergic nerves binds to the pre-junctional alpha-2 adrenoceptor on the non-adrenergic, non-cholinergic (NANC) nerves and inhibits nitric oxide synthesis and release. Blockade of this reaction by selective alpha-2 receptor antagonists (e.g. yohimbine or delequamine) will enhance nitric oxide release, facilitating erection. Finally, cholinergic nerves pre-junctionally inhibit norepinephrine release from the adrenergic nerve and stimulate the NANC nerve to increase nitric oxide synthesis and release. These observations indicate that different neurotransmitters regulate the adrenergic neurotransmission pathway. Based on the above concepts for pre-junctional and post-junctional regulation of smooth muscle tone, the most efficacious strategy to reduce adrenergic activity and facilitate penile erection is to combine alpha-1 and alpha-2 adrenergic receptor antagonists. In this case, any enhancement of norepinephrine release is of little importance because the alpha-1 receptor antagonist will impede this vasoconstrictor response. This will also enhance the release of nitric oxide, which increases smooth muscle relaxation and decreases contraction resulting in penile erection.     

Experimental study of verapamil on the relaxation of isolated human corpus cavernosum tissues

Aim： To evaluate the relaxant effect of verapamil on human corpus cavernosum in vitro and to assess the drug＇s potential as a treatment for erectile dysfunction （ED）. Methods： Preparations of the human corpus cavernosum were obtained from recently deceased young men who had had normal erectile function. The isometric tension and detailed curves were recorded when contractions induced by 10 mmol/L phenylephrine were reduced by different doses of verapamil or the vehicle control （sterile water）. The tension of human corpus cavernosum preparations are described as a percentage of their top tension before adding verapamil or the vehicle. ANOVA and least significant difference tests were used for statistical analysis. Results： Doses of 1μmol/L, 10 μmol/L and 100 μmol/L verapamil resulted in relaxation of （35.28 ± 7.96）%, （55.91 ± 6.41）%, （85.68 ± 4.16）% after 30 min, respectively. The vehicle control at the same time point produced relaxation of （-0.06 ± 10.57）% （P 〈 0.05）. Conclusion： Verapamil is significantly effective in relaxing normal human corpus cavernous smooth muscle induced by phenylephrine in vitro and the relaxant effect depends on the concentration of verapamil. （Asian J Androl 2006 Mar; 8： 195-198）     

Ultrastructural effect of sildenafil citrate on corpus cavernosum and other genital organs in female rats

Aim: To determine the ultrastructural effects of sildenafil on the female genital organs. Methods: Twenty female cycling Wistar albino rats weighing 250±20 g were randomly divided into two groups of 10 each. Rats of one group were gavaged with 0.5 mg·kg-1·d-1 of sildenafil 3 days in a week for 4 weeks and the other served as the controls. After cessation of treatment animals were sacrificed by cervical dislocation under methoxyflurane anaesthesia. The clitoris, vagina, uterus and bartholin glands were taken at the estrous and were fixed with 10 % formalin solution for light microscopy and 2.5 % glutaraldehyde and osmic acid for electron microscopy. Results: Under the light microscope, the fibrocollageous tissue was found increased, the capillaries enlarged and the connecting tissue elements increased in the corpus cavernosum in the treated group. On electron microscopy, increased connective tissue, fibroblasts with notched nucleus, shorten immature collagen fibers without striation were seen. Abundant     

Effects of vasoactive drugs on isolated rabbit corpus cavernosum penis

Recently, intracavernous injection of some vasoactive drugs has been performed for the diagnosis and treatment of impotence. Despite extensive studies the mechanism of erection is still obscure. Therefore, the author studied the effects of some vasoactive drugs on isolated rabbit corpus cavernosum penis. Norepinephrine, phenylephrine or clonidine caused contraction of isolated rabbit corpus cavernosum strips in a concentration-dependent manner. This contractile effect was more potent with norepinephrine and phenylephrine than with clonidine. Prazosin was more effective than yohimbine in inhibiting norepinephrine-induced contractions. Papaverine and verapamil strongly relaxed the strips contracted by norepinephrine. Prostaglandin E1 also showed a relaxant effect. Low concentrations of isoproterenol caused relaxation, but in high concentrations it caused contraction. Acetylcholine relaxed norepinephrine-contracted strips in a concentration-dependent manner. Although the relaxant effect of acetylcholine was weaker than that of papaverine at high concentrations, acetylcholine and papaverine were almost equally effective at low concentrations. Vasoactive intestinal polypeptide relaxed the strips, and it was significantly more potent than papaverine. These findings suggest that both postsynaptic alpha 1-adrenoceptors and alpha 2-adrenoceptors are present in rabbit corpus cavernosum penis, and that alpha 1-adrenoceptors are predominant. The flaccid state of the rabbit penis seems to be maintained mainly by alpha 1-adrenoceptors. Verapamil seems to be useful for the diagnosis and treatment of impotence as papaverine. Acetylcholine and vasoactive intestinal polypeptide may be neurotransmitters involved in erection.     

Effect of hydrogen sulphide‐donating sildenafil (ACS6) on erectile function and oxidative stress in rabbit isolated corpus cavernosum and in hypertensive rats

OBJECTIVE

To study the effect of the H₂S‐donating derivative of sildenafil (ACS6) compared to sildenafil citrate and sodium hydrosulphide (NaHS) on relaxation, superoxide formation and NADPH oxidase and type 5 phosphodiesterase (PDE5) expression in isolated rabbit cavernosal tissue and smooth muscle cells (CSMCs), and in vivo on indices of oxidative stress induced with buthionine sulphoximine (BSO).

MATERIALS AND METHODS

Relaxation was studied in an organ bath in response to carbachol and after incubation with interleukin‐1β for 12 h. CSMCs were incubated with tumour‐necrosis factor‐α or the thromboxane A₂ (TXA₂) analogue, U46619, with or with no sildenafil citrate, ACS6 or NaHS for 16 h. Superoxide formation and the expression of p47^phox (an active subunit of the NADPH oxidase complex) and PDE5 protein was then assessed using Western blotting. Rats were also treated with BSO (with or with no sildenafil citrate or ACS6) for 7 days; cavernosal cGMP, cAMP, glutathionine and plasma TXA₂ and 8‐isoprostane F_2α was measured by enzyme‐linked immunosorbent assay.

RESULTS

ACS6 and sildenafil citrate relaxed cavernosal smooth muscle equipotently; NaHS alone had little effect at up to 100 µm . The formation of superoxide and expression of p47^phox and PDE5 was reduced by ACS6, sildenafil citrate and NaHS (order of potency: ACS6 > sildenafil citrate > NaHS). The effects of ACS6 were blocked by inhibitors of protein kinase A (PKA) and PKG. In rats treated with BSO, both ASC6 and sildenafil citrate reduced the increased plasma levels of TXA₂ and 8‐isoprostane F_2α but increased cGMP, cAMP and glutathionine levels in corpus cavernosum.

CONCLUSIONS

By virtue of a dual action on PKA and PKG activation, ACS6 not only promotes erection, acutely, but might also have a long‐term beneficial effect through inhibition of oxidative stress and downregulation of PDE5.     

Hemihypertrophy of the human corpus cavernosum.

Hemihypertrophy of the right corpus cavernosum and its accompanying thickened tunica albuginea are responsible for the left lateral deviation in congenital curvature of the penis. Surgical correction is more predictable when the lengths of the dorsal and ventral curvatures of the corpora cavernosa are known.     

Fine structure of the human corpus cavernosum

This paper demonstrates the ultrastructure of the human corpus cavernosum from eight male transexuals (aged 20 to 30 years) undergoing penectomy. The presence of collagen, smooth muscle, endothelial cells lining cavernous spaces, mast cells, and different types of nerve terminals, including those of a nonadrenergic and noncholinergic type, are illustrated.     

Purinergic modulation of human corpus cavernosum relaxation

The activation of P2Y(6) receptors has been previously reported to cause vascular smooth muscle constriction and relaxation. The aim of our study was to determine the effect of P2Y(6) receptor subtype activation on human cavernosal function. Cavernosal tissue was obtained from 23 patients undergoing gender reassignment surgery. Immunohistochemistry (IHC) and Western blotting were used to determine the presence of P2Y(6) receptors in corpus cavernosal tissue. The effects of UDP (a selective P2Y(6) receptor agonist) before and after the addition of distilled water (control), cibacron blue 3GA (CB, a P2Y(6) receptor antagonist; 10(-4) m) or N-nitro-L-arginine methyl esther (L-NAME, a NO synthase inhibitor; 10(-4) m) were assessed on phenylephrine (PE; 10(-4) m) pre-contracted cavernosal strips using organ baths. Electrical field stimulation (EFS; 0.5-32 Hz) was performed in the absence and presence of CB to determine neuronal-mediated P2Y(6) receptor responses. IHC and Western blotting revealed the presence of P2Y(6) receptors on cavernosal sections. UDP at 10(-4) m and 10(-3) m induced a 5% and 16% relaxation of the PE-mediated response (both p < 0.0001), respectively, which was significantly blocked by CB (48% reduction of the UDP 10(-3) m response, p < 0.002) but not affected by L-NAME. EFS-induced relaxations of pre-contraction strips were not significantly altered by CB. We have found the presence of P2Y(6) receptors in human cavernosal tissues, that when activated induce cavernosal smooth muscle cell relaxation via non-neuronal and non-nitric oxide dependent mechanism. Further investigation is needed to establish whether P2Y(6) receptors play a physiological role in penile erection.     

Relaxant effects of some benzothiazolinone derivatives on isolated rabbit corpus cavernosum

 In the present study, two 6-(fluorobenzoyl)-3-piperazinomethyl-2-benzothiazolinone derivatives were synthesized and their relaxant effects on isolated rabbit corpus cavernosum investigated. Compounds Y-16 and Y-21 can alter the ability of corpus cavernosum smooth muscle to contract. Strips of rabbit corpus cavernosum smooth muscle were mounted in isolated tissue baths for measurement of isometric contractile force. Compounds (10⁻⁶–10⁻³ M) did not cause contraction but induced relaxation in precontracted corpus cavernosum smooth muscle. Neither N-nitro-l-arginine methylester (L-NAME) nor indomethacin affected the relaxant effect of these compounds. Glibenclamide and tetraethylammonium chloride (TEA) also did not influence the relaxation induced by the compounds. In conclusion, in isolated rabbit corpus cavenosum, Y16 and Y21 have a relaxant potency equal or superior to known vasoactive agents. Further investigations are needed to show the importance of these effects for the diagnosis and treatment of erectile dysfunction. Received: 5 December 2000 / Accepted: 5 March 2001     

Inhibition of sympathetic neuroeffector transmission in human corpus cavernosum

Study Type – Aetiology (case control) Level of Evidence 2b What's known on the subject? and What does the study add? In the present study the mechanisms regulating EFS‐evoked neurogenic contraction in the human corpus cavernosum (HCC) were investigated. Overall, our data adds to current knowledge that the NO‐independent heme dependent activation of sGC and the RhoA/Rho‐kinase signaling pathways play an important role in the regulation of neurogenic contractile activity in HCC tissue.

OBJECTIVE

• ? To investigate the mechanisms of adrenergically mediated smooth muscle contraction in the human corpus cavernosum (HCC) using an organ bath approach.

METHODS

• ? Human corpus cavernosum specimens were obtained from patients (aged 59–72 years) with erectile dysfunction (ED), undergoing penile prosthesis implantation surgery.
• ? Isolated HCC strips (1 × 1 × 6 mm) were suspended in tissue bath chambers for isometric tension recording.
• ? The effects of various drugs on neurogenic contractions evoked by electrical field stimulation (EFS) were investigated. The drugs included nitric oxide (NO) donors, phosphodiesterase 5 (PDE5) inhibitor, Rho kinase (ROCK) inhibitor, NO‐independent stimulator, L‐type Ca2+ channel blocker and α‐receptor antagonist.

RESULTS

• ? Pre‐incubation with the NO donor sodium nitroprusside (SNP; 10⁴ M) significantly reduced the initial peak increase in tension evoked by EFS (by 71%, P < 0.05). The PDE5 inhibitor sildenafil (10^?4 M) reduced the increase in tension by 69%, while a combination of sildenafil and ROCK inhibitor, fasudil, inhibited tension by 81%.
• ? The EFS‐induced contractile response at 80 Hz was decreased by 65% with fasudil and by 70% with isradipine (P < 0.001), while a combination of these drugs decreased the response by 88%. An NO‐independent stimulator soluble guanylate cyclase (sGC), BAY 41‐8543, significantly reduced the response (by 82%, P < 0.001) Phentolamine, an α‐receptor antagonist, nearly eliminated the contractile response (98%, P < 0.001).

CONCLUSIONS

• ? These data suggest that neurogenic contractions are mediated by an increase in Ca(2+) influx via L‐type voltage‐gated Ca(2+) channels and that an increase in Ca(2+) sensitivity is mediated by the ROCK pathway and the PDE5 enzyme system as well as by the inhibitory NO/sGC/cGMP pathway.
• ? The neurogenic contractile response in HCC is mediated by several intracellular pathways, including adrenergic receptors, Ca(2+) entry, Ca(2+) sensitization and activation of the PDE5 enzyme. The Rho‐kinase (ROCK) inhibitor fasudil, L‐type Ca(2+) channel antagonist isradipine, and PDE5 inhibitor sildenafil, as well as a NO‐independent stimulator of sGC, had similar inhibitory effects, suggesting parallel mechanisms in the HCC.

     

A canine model for hemodynamic study of isolated corpus cavernosum

We developed a canine model which permits hemodynamic study of the isolated corpus cavernosum. The arterial and venous flow to the corpus cavernosum was measured and pressure was measured in each corpus cavernosum separately. To provide controlled inflow to the corpora, each side was perfused separately with the aorta clamped. It was demonstrated that arterial and nerve supply to the corpus cavernosum is crossed. During unstimulated corporal perfusion, venous outflow from the corpora increased with increased perfusion rate up to a maximum of 40 ml./min. Following pelvic nerve stimulation, intracorporal pressure increased at much lower rates of perfusion. Moreover, it was noted that intracorporal pressure was not transmitted from one side to the other. Thus, in the canine model, each corpus cavernosum may act as a control for the contralateral one. The technique we used to measure venous outflow from the corpora cavernosa, previously undescribed, permits accurate depiction of the hemodynamics of penile erection.     

Relaxation of isolated corpus cavernosum induced by smooth-muscle relaxant drugs

Summary Intracavernous injection of vasoactive substances are used in the treatment and investigation of impotence. We studied the effects induced by some pharmacological agents on strips of human erectile tissue. Specimens of corpus cavernosum were obtained from 16 men undergoing cystectomy or penectomy for bladder or penile malignancy. Strip preparations were mounted in thermostically controlled baths containing Krebs solution. Pharmacologic effects were monitored by means of an isotonic transducer. Papaverine was shown to be the substance able to cause the biggest relaxation effect. The authors compared the action of other drugs having a relaxant effect, studied the antagonist effects of epinephrine and dopamine on the pharmacologically relaxed preparations, and stressed that the relaxation of the erectile tissue has a determinant role in the appearance and maintenance of erection.     

Relaxation effects of adrenomedullin in isolated rabbit corpus cavernosum smooth muscle

OBJECTIVES: To clarify the pharmacological effects of adrenomedullin, a potent vasodilator and hypotensive peptide isolated from human phaeochromocytoma cells, on corpus cavernosal smooth muscle in vitro, as the intracavernosal injection of adrenomedullin induces penile erection in the anaesthetized cat. MATERIALS AND METHODS: The effects of adrenomedullin were investigated in isolated muscle strips from New Zealand rabbit corpus cavernosum smooth muscle pre-contracted with phenylephrine alone, in the presence of indomethacin (cyclooxygenase inhibitor), Nomega-nitro l-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor), and K+-channel blockers. RESULTS: Adrenomedullin caused relaxation of isolated pre-contracted rabbit corpus cavernosum strips in a concentration-dependent manner. The response of corpus cavernosum was unaffected L-NAME, indomethacin and K+-channel blockers. CONCLUSION: The relaxation exerted by adrenomedullin in rabbit corporal tissue may arise from the effect of the drug on its specific receptors and/or calcitonin gene-related peptide-1 receptors. The relaxant effect of adrenomedullin might lead to novel clinical applications for erectile dysfunction.