Animal Models of Erectile Dysfunction

Petter Hedlund1, Kenshi Matsumoto1, Karl‐Erik Andersson1

1 Lund University Hospital, Lund
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.41
DOI:  10.1002/0471141755.ph0541s29
Online Posting Date:  July, 2005
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

The neuroanatomy of the rat, as well as the morphology of the rat corpus cavernosum, is well characterized. Several molecular biological methods, as well as in vitro preparations, are available for the corpus cavernosum (CC) from rats or mice, and functional investigations of the erectile tissues from these species have revealed similar responses to activation of nerves, endothelium, or pharmacological agents compared with other mammals. By recording intracavernous pressure (ICP), erectile responses to stimulation of nerves at peripheral sites can be evaluated objectively in anesthetized animals. It is thereby possible to isolate and study the effects of regulatory mechanisms of the autonomic nervous system on erection, and to quantify the effect of pharmacological modulation on nerveā€induced responses as changes in ICP. In the conscious rodent model, erectile responses include activities in supraspinal and spinal regulatory units, which lead to activation of both autonomic and somatic pathways destined for the CC or the penile striated muscles. These components can be evaluated by recording ICP in conscious animals, allowing the investigator to avoid possible deleterious effects of anesthesia on supraspinal and spinal transmitter pathways that may be involved in the regulation of erection.

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Basic Protocol 1: Direct Measurement of Intracavernous and Intraarterial Pressures in the Anesthetized Rat
  • Alternate Protocol 1: Direct Measurement of Intracavernous and Intraarterial Pressures in the Anesthetized Mouse During Erections
  • Basic Protocol 2: Direct Measurement of Intracavernous Pressure in the Conscious and Freely Moving Rat During Erections
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

Basic Protocol 1: Direct Measurement of Intracavernous and Intraarterial Pressures in the Anesthetized Rat

  Materials
  • Heparinized saline: 100 IU/ml heparin (Leo Pharma) in 0.9% (w/v) NaCl
  • Male rats (200 to 350 g)
  • 20 mg/ml xylazine (e.g., Rompun, Bayer)
  • 50 mg/ml ketamine (e.g., Ketalar, Parke Davis)
  • Preoperative skin disinfectant (e.g., 5 mg/ml chlorhexidine (Fresenius Kabi), 70% isopropyl alcohol, alcohol prep pads)
  • 0.9% (w/v) NaCl (normal saline)
  • 3, 10, 30, 100, and 300 µg/kg apomorphine (Sigma)
  • Methylene blue
  • 1% mepivacaine (Carbocain, AstraZeneca)
  • Platinum wire (1‐mm diameter)
  • Insulated copper wire (1‐ to 2‐mm diameter)
  • Soldering iron
  • Heat‐shrinking, electrically insulating rubber tubing (3‐mm i.d.)
  • Glass pipets (2‐ to 3‐mm i.d., 1‐mm wall thickness)
  • Metal paper clip (medium size)
  • Fine‐metal file
  • Rubber bands with circumference of ∼10 cm
  • PE‐10 and ‐50 polyethylene tubing (Becton Dickinson)
  • 23‐ and 27‐G (11 2 in.) hypodermic needles (BD Microlance or equivalent)
  • Needle pins
  • 1‐ and 5‐ml syringes (e.g., Becton Dickinson)
  • Pressure transducers (e.g., Spectramed Statham PE22 or equivalent)
  • Digital chart recorder (e.g., Grass Instruments with Polyview software or equivalent)
  • Three‐way stopcocks (e.g., World Precision Instruments)
  • Thermostatically controlled experimental table
  • Dissecting microscope (e.g., Olympus)
  • Cotton gauze compresses
  • Cotton‐tipped applicators
  • Surgical tape (e.g., Johnson & Johnson)
  • Scalpel handle for blades nos. 20 to 25 (e.g., World Precision Instruments)
  • Scalpel blade, no. 22 (e.g., Swann‐Morton)
  • Operating scissors, 14.4 cm (e.g., Rudolf RU)
  • Vannas microscissors, 7‐mm blades (e.g., World Precision Instruments)
  • McPherson‐Vannas microscissor, 3‐mm straight blades (e.g., World Precision Instruments)
  • Tissue forceps, 12.5 cm, 1 × 2 teeth (e.g., World Precision Instruments)
  • Adson forceps, 12 cm (e.g., World Precision Instruments)
  • Dumont tweezers, 11 cm, 0.1 × 0.06 mm tip (e.g., World Precision Instruments)
  • Dumont tweezers, 11 cm, 0.05 × 0.01 mm, 45° tip (World Precision Instruments)
  • Olsen‐Hegar needle holder, 14 cm (e.g., World Precision Instruments)
  • Mosquito hemostatic forceps, 9 cm, straight (e.g., World Precision Instruments)
  • 5‐0 and 3‐0 silk suture (e.g., Serag Wiessner)
  • Crocodile clamps
  • Square pulse stimulator (e.g., Grass Instruments S48 or equivalent)
  • Tripod with holding arms (medium)
  • Needlenose pliers

Alternate Protocol 1: Direct Measurement of Intracavernous and Intraarterial Pressures in the Anesthetized Mouse During Erections

  • Male mice (25 to 35 g)

Basic Protocol 2: Direct Measurement of Intracavernous Pressure in the Conscious and Freely Moving Rat During Erections

  Materials
  • Trochar (e.g., 1.40‐mm i.d., 1.45‐mm o.d.; World Precision Instruments)
  • Woven surgical tape (e.g., Johnson & Johnson)
  • Disposable butane lighter
  • Rat metabolic cage
  • 5‐0 nonabsorbable polyfilament silk suture on a noncutting C‐1 needle (Ethicon)
  • Additional reagents and equipment for catheter construction, drug administration, and equipment set‐up (see protocol 1)
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
   Andersson, K.‐E., Gemalmaz, H., Waldeck, K., Chapman, T., Tuttle, J.B., and Steers, W.D. 1999. The effect of sildenafil on apomorphine‐induced increases in intracavernous pressure in the conscious rat. J. Urol. 161:1707‐1712.
   Bivalaqcua, T.J., Usta, M.F., Matern, R.V., Sanabria, J., Champion, H., and Hellstrom, W.J.G. Gene transfer of endothelial nitric oxide synthase partially restores NO synthesis and erectile function in the streptozotocin diabetic rat. 2002. Int. J. Impot. Res. 14(Suppl. 4):S007 (P‐008).
   Calabro, A., Italiano, G., Pescatori, E., Marin, A., Geatano, O., Abatangelo, G., Abatangelo, G., and Pagano, F. 1996. Physiological aging and penile erectile function: A study in the rat. Eur. Urol. 29:240‐244.
   Chitaley, K., Webb, R.C., Dorrance, A.M., and Mills, T.M. 2001. Decreased penile erection in DOCA‐salt and stroke prone‐spontaneously hypertensive rats. Int. J. Impot. Res. 13(Suppl 5):S16‐20.
   Christ, G.J., Rehman, J., Day, N., Salkoff, L., Valcic, M., Melman, A., and Geliebter, J. 1998. Intracorporal injection of hSlo cDNA in rats produces physiologically relevant alterations in penile function. Am. J. Physiol. 275:H600‐H608.
   Dail, W.D. 1993. Autonomic innervation of male reproductive genitalia. In The Autonomic Nervous System—Nervous Control of the Urogenital System, Vol 6. (C.A. Maggi, ed.) pp. 69‐101. Harwood Academic Publishers, London.
   De Groat, W.C. and Booth, A.M. 1993. Neuronal control of penile erection. In The Autonomic Nervous System—Nervous Control of the Urogenital System, Vol 6. (C.A. Maggi, ed.) pp. 465‐513. Harwood Academic Publishers, London.
   Hart, B.L. and Melese‐D'Hospital, P.Y. 1983. Penile mechanisms and the role of the striated penile muscles in penile reflexes. Physiol. Behav. 31:807‐813.
   Hedlund, P., Alm, P., and Andersson, K.‐E. 1999. NO‐synthase in cholinergic nerves and NO‐induced relaxation in the rat isolated corpus cavernosum. Br. J. Pharmacol. 126:349‐360.
   Hedlund, P., Aszodi, A., Pfeifer, A., Alm, A., Hofmann, F., Fässler, R., and Andersson, K.‐E. 2000. Erectile dysfunction in cGMP protein kinase I deficient mice. Proc. Natl. Acad. Sci. U.S.A. 97:2349‐2354.
   Martinez‐Pineiro, L., Brock, G., Trigo‐Rocha, F., Hsu, G.L., Lue, T.F., and Tanagho, E.A. 1994. Rat model for the study of penile erection: Pharmacologic and electrical‐stimulation parameters. Eur. Urol. 25:62‐70.
   Mizusawa, H., Hedlund, P., Håkansson, A., Alm, P., and Andersson, K.‐E. 2001. Morphological and functional in vitro and in vivo characterization of the mouse corpus cavernosum. Br. J. Pharmacol. 132:1333‐1341.
   Mizusawa, H., Hedlund, P., and Andersson, K.‐E. 2002. Alpha‐Melanocyte stimulating hormone and oxytocin induced penile erection and intracavernous pressure increases in the rat. J. Urol. 167:757‐760.
   Paxinos, G.T. and Watson, C. 1998. The Rat Brain in Stereotaxic Coordinates. Academic Press, New York.
   Quinlan, D.M., Nelson, R.J., Partin, A.W., Mostwin, J.L., and Walsh, P.C. 1989. The rat as a model for the study of penile erection. J. Urol. 141:656‐661.
   Steers, W.D. 1994. Rat: Overview and innervation. Neurourol. Urodyn. 13:97‐118.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library