PURPOSE: The goal of this study was to investigate the effects of luteinizing hormone-releasing hormone(LHRH) agonist treatment on erectile function in an animal model. MATERIALS AND METHODS: New Zealand White male rabbits were either kept intact(control), surgically orchiectomized, or treated for 2, 4, or 8 weeks with the LHRH agonist leuprolide acetate(107microgram/kg/mo). Plasma testosterone levels were measured by enzyme-linked immunosorbent assay. Nitric oxide synthase activity in the total tissue extract was determined by measuring conversion of L-[14C(U)]arginine to [14C]citrulline and nitric oxide. Arginase activity in cytosolic extract was assessed by the Ruegg and Russel method. Erectile function was assessed by continuously recording systemic arterial pressure(SAP) and intracavernosal blood pressure(ICP) and determining the ICP:SAP ratios in response to electrical stimulation of the pelvic nerve at frequencies of 2.5 to 32 Hz. RESULTS: At 2 weeks, plasma testosterone levels of the orchiectomized and leuprolide acetate-treated animals were 12.8% and 57.4% of those in intact control animals, respectively. Androgen deprivation by orchiectomy or leuprolide acetate treatment reduced ICP at all frequencies tested but did not alter SAP. Administration of the phosphodiesterase type 5 inhibitor vardenafil(10microgram/kg) did not enhance ICP in orchiectomized or leuprolide acetate-treated animals. Nitric oxide synthase and arginase activities in the corpus cavernosum were not significantly altered by orchiectomy or leuprolide acetate. Masson trichrome staining of erectile tissue from androgen-ablated animals showed a reduction in smooth muscle content. CONCLUSIONS: Androgen deprivation achieved by orchiectomy or leuprolide acetate treatment adversely affects penile hemodynamics and erectile function without producing significant changes in the activities of nitric oxide synthase or arginase. We conclude that androgen deprivation by LHRH agonist produces structural alterations in the corpus cavernosum leading to corporal veno-occlusive dysfunction.
Androgens ; Animals ; Arginase ; Cytosol ; Electric Stimulation ; Enzyme-Linked Immunosorbent Assay ; Erectile Dysfunction ; Gonadotropin-Releasing Hormone* ; Hemodynamics ; Humans ; Leuprolide ; Lutein ; Male ; Models, Animal ; Muscle, Smooth ; New Zealand ; Nitric Oxide ; Nitric Oxide Synthase ; Orchiectomy ; Plasma ; Rabbits ; Testosterone

PURPOSE: Phosphodiesterase type 5 (PDE type 5) is the predominant enzyme responsible for cGMP hydrolysis in trabecular smooth muscle. Activation of PDE type 5 terminates NO-induced, cGMP-mediated smooth muscle relaxation, resulting ultimately in restoration of basal smooth muscle contractility and penile flaccidity. Sildenafil citrate and vardenafil hydrochloride have been shown to be potent, reversible and selective PDE type 5 inhibitors in penile smooth muscle cells with a Ki of 14.7 nM and 4.5 nM, respectively. The differences in the inhibition constants suggested that sildenafil and vardenafil may have different efficacy in facilitating penile erection in response to sexual stimulation. The objective of this study was to compare the time of onset and efficacy of vardenafil and sildenafil in facilitating/enhancing penile erection in an anesthetized rabbit model. MATERIALS AND METHODS: Penile hemodynamics were assessed in male New Zealand White rabbits (3.5-4.0 kg) by intracavernosal pressure (ICP) monitoring before or after administration of varying doses of vardenafil or sildenafil. Drugs were administered intravenously or intracavernosally. Penile erections were elicited by submaximal electrical stimulation (2.5 or 6 Hz) of the pelvic nerve. ICP recordings were normalized to mean systemic systolic arterial pressure. RESULTS: Intravenous administration of 1, 3, 10 or 30ng/kg of vardenafil or sildenafil facilitated pelvic nerve mediated penile erection in the anesthetized rabbits. ICP increased in a dose dependent fashion with both agents and reached peak response at about 5 minutes and lasted over 30 minutes at all doses tested. Intracavernosal injection of 10ng/kg of vardenafil or sldenafil enhanced pelvic nerve mediated erection at 2.5 Hz. At all doses investigated, vardenafil was more effective than sildenafil in facilitating pelvic nerve-mediated penile erection. Vardenafil had a significant effect on changes in systemic blood pressure when compared to sildenafil. CONCLUSIONS: In this report, we demonstrate that vardenafil is more effective than sildenafil in potentiating penile erection, at equivalent doses as indicated by the maximal increase in ICP over time.
Administration, Intravenous ; Arterial Pressure ; Blood Pressure ; Citric Acid ; Electric Stimulation ; Erectile Dysfunction ; Hemodynamics ; Humans ; Hydrolysis ; Male ; Muscle, Smooth ; Myocytes, Smooth Muscle ; Penile Erection* ; Rabbits ; Relaxation ; Sildenafil Citrate ; Vardenafil Dihydrochloride

PURPOSE: This study was designed to determine the validity and usefulness of laser oximetry in measuring changes in penile hemodynamics for assessment of erectile function. MATERIALS AND METHODS: Anesthetized male New Zealand White rabbits (3.5~4.0 kg) were divided into two groups and penile hemodynamics were assessed by either laser oximetry (total hemoglobin, oxyhemoglobin, deoxyhemoglobin concentration and oxygen saturation) or intracavernosal pressure (ICP) monitoring before, during and after penile erection induced by pelvic nerve stimulation (PNS) or intracavernosal administration of phentolamine (0.05~1.0 mg/kg), nitroprusside (1~30ng/kg), papaverine (0.1~1.0 mg/kg) or sildenafil (3~150ng/kg). ICP recordings were normalized to systemic systolic arterial pressure. RESULTS: PNS caused significant frequency-dependent increases in penile ICP. PNS also caused significant increases in penile tissue hemoglobin (total and oxy) concentrations and tissue oxygen saturation in a frequency-dependent manner. These changes were correlated with frequency-dependent increases in ICP. The duration of recorded responses (changes in hemoglobin concentration or ICP) increased with increasing frequency of nerve stimulation. Intracavernosal administration of phentolamine, nitroprusside, papaverine and sildenafil produced significant increases in ICP, tissue hemoglobin, oxygen saturation and duration of response as a function of increasing drug concentration. CONCLUSIONS: Laser oximetry permits reproducible and valid assessment of changes in penile hemodynamics comparable to classical intracavernosal pressure measurements. Thus, we consider laser oximetry a reliable technique in evaluating penile hemodynamics. Its sensitivity in detecting small changes in oxyhemoglobin concentration and its non-invasive nature makes it advantageous over invasive METHODS such as intracavernosal pressure monitoring and laser Doppler flowmetry.
Arterial Pressure ; Hemodynamics* ; Humans ; Laser-Doppler Flowmetry ; Male ; Nitroprusside ; Oximetry* ; Oxygen ; Oxyhemoglobins ; Papaverine ; Penile Erection ; Phentolamine ; Rabbits ; Spectroscopy, Near-Infrared ; Sildenafil Citrate