Direct effects of selective type 5 phosphodiesterase inhibitors alone or with other vasodilators on the erectile response in cats

Paul C. Doherty, Trinity Bivalacqua, Hunter C. Champion, Philip J. Kadowitz, Beverly Greenwood Van Meerveld, I. Berzetei-Gurske, Wayne J G Hellstrom

Research output: Contribution to journalArticle

Abstract

Purpose: Zaprinast, dipyridamole and sildenafil were injected into the corpora cavernosa of cats to determine whether changes in the steady state level of cyclic guanosine monophosphate (cGMP) induced by inhibiting type 5 phosphodiesterase would cause an erectile response. Materials and Methods: Increases in intracavernous pressure, penile length and erectile response duration were determined after intracavernous injection of the type 5 cGMP specific phosphodiesterase inhibitors zaprinast, dipyridamole and sildenafil as well as combined zaprihast and prostaglandin E1 (PGE1), and zaprinast and sodium nitroprusside. Systemic arterial pressure was concurrently assessed in these experiments. All responses to phosphodiesterase inhibitors were compared to a control triple drug combination of 1.65 mg. papaverine, 0.5 μg. PGE1 and 25 μg. phentolamine. Results: Each selective type 5 phosphodiesterase inhibitor caused dose related increases in intracorporeal pressure and penile length. However, none of the compounds was as effective as the control drug combination of papaverine, phentolamine and PGE1. Combining zaprinast with sodium nitroprusside led to further increases in pressure and erectile response duration that more closely resembled the control drug response. Combining zaprinast with PGE1 led to a response that was indistinguishable from the control response. Conclusions: The results of these feline studies establish that administering a type 5 phosphodiesterase inhibitor without concomitant administration of a nitric oxide donor or stimulation of the cavernous nerves may have a direct effect on the erectile response. These data also suggest that combining a selective type 5 phosphodiesterase inhibitor with PGE1 may be highly effective local therapy for erectile dysfunction and an acceptable alternative to other current forms of treatment.

Original languageEnglish (US)
Pages (from-to)1004-1009
Number of pages6
JournalJournal of Urology
Volume165
Issue number3
StatePublished - 2001
Externally publishedYes

Fingerprint

Phosphodiesterase 5 Inhibitors
Alprostadil
Vasodilator Agents
Cats
Phosphodiesterase Inhibitors
Dipyridamole
Cyclic GMP
Nitroprusside
Pressure
Type 5 Cyclic Nucleotide Phosphodiesterases
Guanosine Monophosphate
Papaverine
Nitric Oxide Donors
Phentolamine
Drug and Narcotic Control
Felidae
Erectile Dysfunction
Drug Combinations
Arterial Pressure
zaprinast

Keywords

  • Cyclic GMP cats
  • Penile erection
  • Penis
  • Phosphodiesterase inhibitors

ASJC Scopus subject areas

  • Urology

Cite this

Doherty, P. C., Bivalacqua, T., Champion, H. C., Kadowitz, P. J., Meerveld, B. G. V., Berzetei-Gurske, I., & Hellstrom, W. J. G. (2001). Direct effects of selective type 5 phosphodiesterase inhibitors alone or with other vasodilators on the erectile response in cats. Journal of Urology, 165(3), 1004-1009.

Direct effects of selective type 5 phosphodiesterase inhibitors alone or with other vasodilators on the erectile response in cats. / Doherty, Paul C.; Bivalacqua, Trinity; Champion, Hunter C.; Kadowitz, Philip J.; Meerveld, Beverly Greenwood Van; Berzetei-Gurske, I.; Hellstrom, Wayne J G.

In: Journal of Urology, Vol. 165, No. 3, 2001, p. 1004-1009.

Research output: Contribution to journalArticle

Doherty, PC, Bivalacqua, T, Champion, HC, Kadowitz, PJ, Meerveld, BGV, Berzetei-Gurske, I & Hellstrom, WJG 2001, 'Direct effects of selective type 5 phosphodiesterase inhibitors alone or with other vasodilators on the erectile response in cats', Journal of Urology, vol. 165, no. 3, pp. 1004-1009.
Doherty, Paul C. ; Bivalacqua, Trinity ; Champion, Hunter C. ; Kadowitz, Philip J. ; Meerveld, Beverly Greenwood Van ; Berzetei-Gurske, I. ; Hellstrom, Wayne J G. / Direct effects of selective type 5 phosphodiesterase inhibitors alone or with other vasodilators on the erectile response in cats. In: Journal of Urology. 2001 ; Vol. 165, No. 3. pp. 1004-1009.
@article{50123d0af36d45fb8d5b4c8e9529c7cb,
title = "Direct effects of selective type 5 phosphodiesterase inhibitors alone or with other vasodilators on the erectile response in cats",
abstract = "Purpose: Zaprinast, dipyridamole and sildenafil were injected into the corpora cavernosa of cats to determine whether changes in the steady state level of cyclic guanosine monophosphate (cGMP) induced by inhibiting type 5 phosphodiesterase would cause an erectile response. Materials and Methods: Increases in intracavernous pressure, penile length and erectile response duration were determined after intracavernous injection of the type 5 cGMP specific phosphodiesterase inhibitors zaprinast, dipyridamole and sildenafil as well as combined zaprihast and prostaglandin E1 (PGE1), and zaprinast and sodium nitroprusside. Systemic arterial pressure was concurrently assessed in these experiments. All responses to phosphodiesterase inhibitors were compared to a control triple drug combination of 1.65 mg. papaverine, 0.5 μg. PGE1 and 25 μg. phentolamine. Results: Each selective type 5 phosphodiesterase inhibitor caused dose related increases in intracorporeal pressure and penile length. However, none of the compounds was as effective as the control drug combination of papaverine, phentolamine and PGE1. Combining zaprinast with sodium nitroprusside led to further increases in pressure and erectile response duration that more closely resembled the control drug response. Combining zaprinast with PGE1 led to a response that was indistinguishable from the control response. Conclusions: The results of these feline studies establish that administering a type 5 phosphodiesterase inhibitor without concomitant administration of a nitric oxide donor or stimulation of the cavernous nerves may have a direct effect on the erectile response. These data also suggest that combining a selective type 5 phosphodiesterase inhibitor with PGE1 may be highly effective local therapy for erectile dysfunction and an acceptable alternative to other current forms of treatment.",
keywords = "Cyclic GMP cats, Penile erection, Penis, Phosphodiesterase inhibitors",
author = "Doherty, {Paul C.} and Trinity Bivalacqua and Champion, {Hunter C.} and Kadowitz, {Philip J.} and Meerveld, {Beverly Greenwood Van} and I. Berzetei-Gurske and Hellstrom, {Wayne J G}",
year = "2001",
language = "English (US)",
volume = "165",
pages = "1004--1009",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Direct effects of selective type 5 phosphodiesterase inhibitors alone or with other vasodilators on the erectile response in cats

AU - Doherty, Paul C.

AU - Bivalacqua, Trinity

AU - Champion, Hunter C.

AU - Kadowitz, Philip J.

AU - Meerveld, Beverly Greenwood Van

AU - Berzetei-Gurske, I.

AU - Hellstrom, Wayne J G

PY - 2001

Y1 - 2001

N2 - Purpose: Zaprinast, dipyridamole and sildenafil were injected into the corpora cavernosa of cats to determine whether changes in the steady state level of cyclic guanosine monophosphate (cGMP) induced by inhibiting type 5 phosphodiesterase would cause an erectile response. Materials and Methods: Increases in intracavernous pressure, penile length and erectile response duration were determined after intracavernous injection of the type 5 cGMP specific phosphodiesterase inhibitors zaprinast, dipyridamole and sildenafil as well as combined zaprihast and prostaglandin E1 (PGE1), and zaprinast and sodium nitroprusside. Systemic arterial pressure was concurrently assessed in these experiments. All responses to phosphodiesterase inhibitors were compared to a control triple drug combination of 1.65 mg. papaverine, 0.5 μg. PGE1 and 25 μg. phentolamine. Results: Each selective type 5 phosphodiesterase inhibitor caused dose related increases in intracorporeal pressure and penile length. However, none of the compounds was as effective as the control drug combination of papaverine, phentolamine and PGE1. Combining zaprinast with sodium nitroprusside led to further increases in pressure and erectile response duration that more closely resembled the control drug response. Combining zaprinast with PGE1 led to a response that was indistinguishable from the control response. Conclusions: The results of these feline studies establish that administering a type 5 phosphodiesterase inhibitor without concomitant administration of a nitric oxide donor or stimulation of the cavernous nerves may have a direct effect on the erectile response. These data also suggest that combining a selective type 5 phosphodiesterase inhibitor with PGE1 may be highly effective local therapy for erectile dysfunction and an acceptable alternative to other current forms of treatment.

AB - Purpose: Zaprinast, dipyridamole and sildenafil were injected into the corpora cavernosa of cats to determine whether changes in the steady state level of cyclic guanosine monophosphate (cGMP) induced by inhibiting type 5 phosphodiesterase would cause an erectile response. Materials and Methods: Increases in intracavernous pressure, penile length and erectile response duration were determined after intracavernous injection of the type 5 cGMP specific phosphodiesterase inhibitors zaprinast, dipyridamole and sildenafil as well as combined zaprihast and prostaglandin E1 (PGE1), and zaprinast and sodium nitroprusside. Systemic arterial pressure was concurrently assessed in these experiments. All responses to phosphodiesterase inhibitors were compared to a control triple drug combination of 1.65 mg. papaverine, 0.5 μg. PGE1 and 25 μg. phentolamine. Results: Each selective type 5 phosphodiesterase inhibitor caused dose related increases in intracorporeal pressure and penile length. However, none of the compounds was as effective as the control drug combination of papaverine, phentolamine and PGE1. Combining zaprinast with sodium nitroprusside led to further increases in pressure and erectile response duration that more closely resembled the control drug response. Combining zaprinast with PGE1 led to a response that was indistinguishable from the control response. Conclusions: The results of these feline studies establish that administering a type 5 phosphodiesterase inhibitor without concomitant administration of a nitric oxide donor or stimulation of the cavernous nerves may have a direct effect on the erectile response. These data also suggest that combining a selective type 5 phosphodiesterase inhibitor with PGE1 may be highly effective local therapy for erectile dysfunction and an acceptable alternative to other current forms of treatment.

KW - Cyclic GMP cats

KW - Penile erection

KW - Penis

KW - Phosphodiesterase inhibitors

UR - http://www.scopus.com/inward/record.url?scp=0035131630&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035131630&partnerID=8YFLogxK

M3 - Article

C2 - 11176530

AN - SCOPUS:0035131630

VL - 165

SP - 1004

EP - 1009

JO - Journal of Urology

JF - Journal of Urology

SN - 0022-5347

IS - 3

ER -