Wilkes N, White S, Stein P, Bernie J, Rajasekaran M
Division of Urology, University of California-San Diego Medical Center, 200 W. Arbor Drive (8897), San Diego, CA 92103-8897, USA.
Int J Impot Res. 2004 Apr;16(2):187-94. doi: 10.1038/sj.ijir.3901149.
To evaluate the association between hypertension, male erectile function, Rho-kinase, and cyclic GMP pathways, we monitored neurogenic erectile response in spontaneously hypertensive (SHR) vs normotensive rats. We also evaluated SHR erectile function before and after intracavernosal injection of either the specific Rho-kinase inhibitor Y-27632 or a combination of Y-27632 and the PDE5 inhibitor zaprinast to prevent cGMP degradation. SHR had lower resting baseline corpus cavernosum pressure and a higher threshold for development of tumescence than normotensive rats. In SHR, Y-27632 administration reversed hypertension-related changes in male erectile function; Rho-kinase antagonism and PDE5 inhibition in combination had a synergistic effect in improving the neurogenic erectile response. Our data indicate that hypertension is associated with impairment in the SHR neurogenic erectile response that may involve a derangement in hemodynamic mechanisms in penile erectile tissue. Rho-kinase inhibition alone or combined with PDE5 inhibition may be of value in treating hypertension-related ED.
为了评估高血压、男性勃起功能、Rho激酶和环磷酸鸟苷（cGMP）信号通路之间的关联，我们监测了自发性高血压大鼠（SHR）与正常血压大鼠的神经源性勃起反应。我们还评估了在海绵体内注射特异性Rho激酶抑制剂Y-27632或Y-27632与磷酸二酯酶5（PDE5）抑制剂扎普司特的组合以防止cGMP降解之前和之后SHR的勃起功能。与正常血压大鼠相比，SHR的静息基线海绵体压力较低，勃起肿胀的阈值较高。在SHR中，给予Y-27632可逆转与高血压相关的男性勃起功能变化；Rho激酶拮抗作用与PDE5抑制作用联合使用在改善神经源性勃起反应方面具有协同效应。我们的数据表明，高血压与SHR神经源性勃起反应受损有关，这可能涉及阴茎勃起组织血流动力学机制的紊乱。单独抑制Rho激酶或与PDE5抑制联合使用可能对治疗高血压相关的勃起功能障碍有价值。
