Table 1.

Assessment of ROCK inhibitors in animal models of disease states associated with ED

Disease state	Effects on RhoA/ROCK	ROCK inhibitor	Effects of ROCK inhibition	Animal model	Reference
Normal physiology	NA	Y-27632	ICI increased ICP in dose-dependent fashion, independent of NO inhibition	Rat Rabbit	30 – 32
Hypertension	Increased RhoA expression in cavernosal tissues	Y-27632 Fasudil Azaindole-1	Systemic treatment improved systemic hypertension via systemic arterial relaxation ICI improved ED, augmented PDE5 inhibitor effects	DOCA rat SHRSP	41,43–45
Diabetes	Increased RhoA activity with decreased eNOS expression Increased apoptosis Increased ROCK-2 activity Increased MAPK Increased ROCK-2 activity and apoptosis in the MPG	Y-27632 RhoA−Adenovirus Fasudil SAR407899 Atorvastatin Testosterone	Improved relaxation independent of exogenous NO inhibition Normalized RhoA expression and erectile response, improved eNOS expression Normalized PTEN, caspase-3 and PKB activities, decreased apoptosis	STZ rabbit STZ rat STZ mouse Rock1−/+ mouse Rock2−/+ mouse Human	26,47,48, 54–56
Ageing	Increased activity with normal expression	RhoA−Adenovirus	Decreased ROCK activity with increased ICP, with improved response to concomitant PDE5 inhibitor treatment	Aged versus young rat	21,58
Prostatectomy	Cavernosal tissue apoptosis and remodelling Increased RhoA and ROCK-2 expression	Y-27632	Increased ICP in dose-dependent manner	Cavernosal nerve-crush rat	24,61,64

Abbreviations: DOCA, deoxycorticosterone acetate–salt; ED, erectile dysfunction; eNOS, endothelial nitric oxide synthase; ICI, intracorporal injection; ICP, intracavernosal pressure; MAPK, mitogen-activated protein kinase; MPG, major pelvic ganglion; NA, not applicable; ^RhoA−adenovirus, adenovirus encoding dominant-negative RhoA mutant; ROCK, Rho-associated protein kinase; SHRSP, stroke prone-spontaneously hypertensive rats; STZ, streptozotocin-induced diabetic; Y-27632, (R)-(+Hrans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide.