Relaxing effects induced by the soluble guanylyl cyclase stimulator BAY 41-2272 in human and rabbit corpus cavernosum

Juliana S. Baracat, Cleber E. Teixeira, Cristina E. Okuyama, Fernanda Priviero, Renato Faro, Edson Antunes, Gilberto De Nucci

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

5-Cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl] -pyrimidin-4-ylamine (BAY 41-2272) is a potent soluble guanylyl cyclase stimulator in a nitric oxide (NO)-independent manner. The relaxant effect of BAY 41-2272 was investigated in rabbit and human corpus cavernosum in vitro. BAY 41-2272 (0.01-10 μM) relaxed both rabbit (pEC50=6.82±0. 06) and human (pEC50=6.12±0.10) precontracted cavernosal strips. The guanylyl cyclase inhibitor (ODQ, 10 μM) caused significant rightward shifts in the concentration-response curves for BAY 41-2272 in rabbit (4.7-fold) and human (2.3-fold) tissues. The NO synthesis inhibitor (N-nitro-L-arginine methyl ester (L-NAME), 100 μM) also produced similar rightward shifts, revealing that BAY 41-2272 acts synergistically with endogenous NO to elicit its relaxant effect. The results also indicate that ODQ is selective for the NO-stimulated enzyme, since relaxations evoked by BAY 41-2272 were only partly attenuated by ODQ. The present study shows that both BAY 41-2272 and sildenafil evoke relaxations independent of inhibition of haem in soluble guanylate cyclase. Moreover, there is no synergistic effect of the two compounds in corpus cavernosum.

Original languageEnglish (US)
Pages (from-to)163-169
Number of pages7
JournalEuropean Journal of Pharmacology
Volume477
Issue number2
DOIs
StatePublished - Sep 12 2003

Fingerprint

Rabbits
Nitric Oxide
Guanylate Cyclase
NG-Nitroarginine Methyl Ester
3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine
Soluble Guanylyl Cyclase
Heme
Enzymes

Keywords

  • BAY 41-2272
  • Corpus cavernosum
  • Nitric oxide (NO)
  • Sildenafil
  • Soluble guanylyl cyclase

ASJC Scopus subject areas

  • Pharmacology

Cite this

Relaxing effects induced by the soluble guanylyl cyclase stimulator BAY 41-2272 in human and rabbit corpus cavernosum. / Baracat, Juliana S.; Teixeira, Cleber E.; Okuyama, Cristina E.; Priviero, Fernanda; Faro, Renato; Antunes, Edson; De Nucci, Gilberto.

In: European Journal of Pharmacology, Vol. 477, No. 2, 12.09.2003, p. 163-169.

Research output: Contribution to journalArticle

Baracat, Juliana S. ; Teixeira, Cleber E. ; Okuyama, Cristina E. ; Priviero, Fernanda ; Faro, Renato ; Antunes, Edson ; De Nucci, Gilberto. / Relaxing effects induced by the soluble guanylyl cyclase stimulator BAY 41-2272 in human and rabbit corpus cavernosum. In: European Journal of Pharmacology. 2003 ; Vol. 477, No. 2. pp. 163-169.
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T1 - Relaxing effects induced by the soluble guanylyl cyclase stimulator BAY 41-2272 in human and rabbit corpus cavernosum

AU - Baracat, Juliana S.

AU - Teixeira, Cleber E.

AU - Okuyama, Cristina E.

AU - Priviero, Fernanda

AU - Faro, Renato

AU - Antunes, Edson

AU - De Nucci, Gilberto

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AB - 5-Cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl] -pyrimidin-4-ylamine (BAY 41-2272) is a potent soluble guanylyl cyclase stimulator in a nitric oxide (NO)-independent manner. The relaxant effect of BAY 41-2272 was investigated in rabbit and human corpus cavernosum in vitro. BAY 41-2272 (0.01-10 μM) relaxed both rabbit (pEC50=6.82±0. 06) and human (pEC50=6.12±0.10) precontracted cavernosal strips. The guanylyl cyclase inhibitor (ODQ, 10 μM) caused significant rightward shifts in the concentration-response curves for BAY 41-2272 in rabbit (4.7-fold) and human (2.3-fold) tissues. The NO synthesis inhibitor (N-nitro-L-arginine methyl ester (L-NAME), 100 μM) also produced similar rightward shifts, revealing that BAY 41-2272 acts synergistically with endogenous NO to elicit its relaxant effect. The results also indicate that ODQ is selective for the NO-stimulated enzyme, since relaxations evoked by BAY 41-2272 were only partly attenuated by ODQ. The present study shows that both BAY 41-2272 and sildenafil evoke relaxations independent of inhibition of haem in soluble guanylate cyclase. Moreover, there is no synergistic effect of the two compounds in corpus cavernosum.

KW - BAY 41-2272

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KW - Sildenafil

KW - Soluble guanylyl cyclase

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