Effect of soluble guanylate cyclase modulators, bay 60-2770 and bay 41-2272 in isolated corpus cavernosum from normotensive and spontaneously hypertensive rats

This study is aimed to verify the effect of soluble guanylate cyclase (sGC) modulators, BAY 60-2770 (activator) and BAY 41-2272 (stimulator) in isolated corpus cavernosum (CC) from normotensive (WKY) and spontaneously hypertensive rats (SHR). Material and Methods: Concentration-response curves to BAY 60-2770 (0.01–10 μM) and BAY 41-2272 (0.01–10 μM) were carried out in the absence and in the presence of sGC inhibitor (ODQ, 10 μM) in tissues pre-contracted with phenylephrine (PE, 10 μM). Potency (pEC50) and maximal response (Emax) values were calculated. In vivo assay was realized by determining basal and stimulated intracavernous pressure (ICP) before and after intracavernosal injection of BAY 60-2770 (350 ng/Kg) or BAY 41-2272 (350 ng/Kg). Protein expression for α1 (Anti-sGC α1 – subunit, 1:500 and beta-1 Anti-sGC β1-subunit, 1:1000) subunits were also assessed. The experimental protocols were approved by the Animal Ethical Committee of UNICAMP (2721-1). Results: BAY 60-2770 and BAY 41-2272 produced concentrationdependent relaxation in isolated CC from WKY (pEC50: 7.01 ± 0.45 and 6.05 ± 0.10; Emax: 99 ± 13 and 76 ± 4 %, n = 5–7, respectively) and SHR (pEC50: 6.99 ± 0.15 and 6.11 ± 0.16; Emax: 95 ± 5 and 87 ± 6%, n = 5–7, respectively). Whereas the addition of ODQ produced a 7-fold rightward shift (P < 0.05) in BAY 41-227-induced relaxation, the pEC50 values of BAY 60-2770 was shift by 5-fold to the left. Protein levels for α1 and β1 subunits of sGC did not differ between WKY and SHR. BAY 60-2770 augmented ICP by 25,9% at 16 Hz only in CC from WKY. BAY 41-2272 did not alter ICP in CC from WKY or SHR. Conclusion: BAY 41-2272 and BAY 60-2770 relaxed corpus cavernosum from hypertensive rats and may constitute a therapeutic option for the treatment of erectile dysfunction. Soluble guanylate cyclase modulators have been proposed as pharmacological tools to differentiate the oxidative state of sGC. In the present study we may speculate that sGC is not oxidized in CC from SHR, as the relaxing response induced by BAY 41-2272 or BAY 60-2770 in CC from SHR did not differ from that of WKY121525