Evaluation of erectile response by continuous measurement of penile diameter in rats.
The present study was performed to determine whether measurement of penile diameter in an in vivo rat model is useful for pharmacologic and physiologic investigations on penile erection. Penile erection induced by electrical stimulation of the cavernous nerve was monitored by measuring the penile diameter sonomicrometrically with a pair of 10-MHz piezoelectric crystals glued to the opposite surfaces of the adventitia of the penile erectile chamber in anesthetized rats. Using this method, we examined the effects of a nitric oxide (NO) synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), and a well-known phosphodiesterase 5 (PDE5) inhibitor, zaprinast, on the maximal developed penile diameter (D-max) and the time from the maximum response to 50% recovery (T50%) of the maximum response as an index of the duration of penile erection. An intravenous injection of L-NAME at a dose of 10 mg/kg significantly inhibited D-max produced by cavernous electrical stimulation at 5 to 50 V, without affecting T50%. Sequential intravenous infusions of 10, 30, 100, and 300 microg/kg/min of zaprinast at 30-min intervals did not show any effect on D-max, heart rate, and systolic arterial pressure, although doses of 100 and 300 microg/kg/min significantly prolonged T50% and the maximum dose decreased diastolic arterial pressure. Moreover, zaprinast produced a more prominent increase in cyclic guanosine monophosphate (cGMP) levels than cyclic adenosine monophosphate levels in the plasma taken at the end of the maximum dose infusion. Measurement of murine penile diameter with a sonomicrometrical device, indicating that a NO-cGMP-PDE5 pathway plays a pivotal role in the penile diameter increase and its maintenance, would be useful for pharmacologic and physiologic investigations on penile erection.
Adachi
H
H
Tsukuba Research Laboratories, Eisai Co., Ibaraki, Japan. h-adachi@hhc.eisai.co.jp
Kodama
K
K
Ishihara
H
H
D000818:Animals; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D010410:Penile Erection / Q000502:physiology*; D010413:Penis / Q000033:anatomy & histology*; D011688:Purinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013010:Sonication; D013997:Time Factors
D004791:Enzyme Inhibitors; D011688:Purinones; D000242:Cyclic AMP; C011145:zaprinast; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester