Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0268318 (ICP)
 10,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Numerous etiological studies have established a positive clinical association between hypertension and erectile dysfunction. However, to date, the mechanism underlying this dysfunction remains to be established. In this study, we demonstrate the presence of erectile dysfunction in two rat models of hypertension, and hypothesize that increased vasoconstrictor signaling via Rho-kinase contributes to the decreased erectile response. We found deoxycorticosterone-salt and stroke prone-spontaneously hypertensive rats to exhibit a decreased erectile response, recorded as intracavernosal pressure/mean arterial pressure (ICP/MAP) upon electrical stimulation of the major pelvic ganglion. As previously shown, inhibition of Rho-kinase activity by intracavernosal injection of the selective inhibitor, Y-27632, resulted in an increase in ICP/MAP. However, Y-27632 was significantly less effective at increasing ICP/MAP in the hypertensive as compared to normotensive rats. Additionally, intracavernosal injection of Y-27632 potentiated the voltage-stimulated increase in ICP/MAP in both hypertensive and normotensive rats, but was less effective at potentiating the voltage-mediated erectile response in the hypertensive rats. Altogether, our data demonstrate a decreased erectile response in a mineralocorticoid and genetic model of hypertension, and suggest the role of increased cell signaling by Rho-kinase in the vasoconstrictor activity of erectile dysfunction associated with hypertension.
 ...
PMID:Decreased penile erection in DOCA-salt and stroke prone-spontaneously hypertensive rats. 1178 42

We investigated whether the effect of Y-27632 to improve the erectile function in SD rats was associated with the degree of the imbalance between nNOS and the Rho-kinase pathways. Western blot analysis was used to evaluate nNOS and Rho-kinase protein expression in 10 young and 10 old SD rats. Imbalance value between nNOS and Rho-kinase protein levels was obtained by subtracting nNOS from Rho-kinase. A 5-V stimulus was given in SD rats before and after the administration of 200 nmol kg(-1) of Y-27632 intracavernosally and ICP/MAP was recorded. The improvement of erectile function induced by Y-27632 was expressed as the margin of ICP/MAP after and before the administration of Y-27632. In young rat group, the contents of nNOS and Rho-kinase protein were 1.7 +/- 0.15 and 1.8 +/- 0.14 respectively. In old rat group, the nNOS protein decreased to 1 +/- 0.15, and in contrast, the Rho-kinase protein increased to 2.6 +/- 0.2. The imbalance value between nNOS and Rho-kinase was 0.2986 +/- 0.1109 and 1.5961 +/- 0.1206 in young and old rat groups. The improvement of erectile function induced by Y-27632 was 0.0500 +/- 0.0294 and 0.3420 +/- 0.660 in young and old rat groups. In all rats, the correlation coefficient between the imbalance value of nNOS and Rho-kinase and the improvement of erectile function was 0.649, P < 0.01. In conclusion, this study suggested that impaired erectile function with ageing in SD rats be associated with the imbalance between nNO and Rho-kinase activity and Y-27632 could improve the erectile function in old SD rats through adjusting this imbalance.
 ...
PMID:Y-27632 improves the erectile dysfunction with ageing in SD rats through adjusting the imbalance between nNo and the Rho-kinase pathways. 1768 64

Spontaneously hypertensive rats (SHR) are characterized by impaired erectile function and overactivity of the procontractile RhoA/Rho-associated, coiled-coil-containing protein kinase (RhoA/ROCK) pathway, as compared with their normotensive counterpart, Wistar-Kyoto rats. By measuring the intracavernous pressure:mean arterial pressure (ICP:MAP) ratio after electrostimulation of the cavernous nerve, we confirmed these findings and showed that responsiveness to sildenafil (25 mg/kg by oral gavage) also is hampered in SHR. A 2-week treatment with atorvastatin (5 and 30 mg/kg) improved the sildenafil-induced ICP:MAP increase and normalized RhoA and ROCK2 overexpression in SHR corpora cavernosa (CC). Conversely, other genes, neuronal nitric oxide synthase (NOS), endothelial NOS, and phosphodiesterase 5, were unaffected. In human fetal smooth muscle cells derived from CC (hfPSMC), atorvastatin inhibited RhoA membrane translocation and ROCK activity, as well as RhoA-dependent biologic functions like cell migration and cell proliferation. Atorvastatin's effect on migration was rescued in a dose-dependent manner by geranylgeranyl pyrophosphate, suggesting the involvement of RhoA geranylgeranylation. In hfPSMC, atorvastatin decreased the expression of RhoA-dependent genes such as ROCK2, desmin, alpha-smooth muscle actin, SM22alpha, and myocardin. In contrast to atorvastatin, elocalcitol, a vitamin D analog that also interferes with RhoA activation in SHR bladder, was unable to restore penile responsiveness to sildenafil. In conclusion, atorvastatin, but not elocalcitol, ameliorates sildenafil-induced penile erections in SHR, likely by interfering with RhoA/ROCK signaling within the penis.
 ...
PMID:Atorvastatin but not elocalcitol increases sildenafil responsiveness in spontaneously hypertensive rats by regulating the RhoA/ROCK pathway. 1769 3

The present study aimed to investigate the changes of Rho-associated kinase (Rho-kinase) and neuronal nitric oxide synthase (nNOS) expression in age-associated erectile dysfunction (ED) in Sprague-Dawley (SD) rats. A total of 100 intact male SD rats were divided into 20 groups according to their age (5-24 months; rats that were the same age in months were in the same group). Erectile response measurements were performed and the functional index intracavernosal pressure/mean arterial pressure (ICP/MAP) was tested, followed by detection of Rho-kinase and nNOS protein by western blot analysis. Finally, correlation analyses of the association between ICP/MAP and Rho-kinase, nNOS, or nNOS/Rho-kinase, as well as between age and nNOS or Rho-kinase, were performed. The functional index ICP/MAP decreased with age in SD rats. Moreover, the expression of nNOS protein decreased, while Rho-kinase expression increased, indicating that the nNOS/Rho-kinase ratio decreased with age. The Pearson's correlation coefficients for the association between ICP/MAP and Rho-kinase, nNOS and nNOS/Rho-kinase ratio were -0.917, 0.853 and 0.937, respectively (P<0.01). Furthermore, nNOS was found to be significantly negatively correlated with age (r=-0.855; P<0.01), whereas Rho-kinase was positively correlated with age (r=0.943; P<0.01). Age-associated ED was therefore correlated with decreased nNOS and increased Rho-kinase, indicating that the nNOS/Rho-kinase ratio may be used as a candidate indicator of age-associated ED.
 ...
PMID:Association of nNOS and Rho-kinase with age-associated erectile dysfunction in Sprague-Dawley rats. 2845 Sep 53