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

We investigated the feasibility of using the rabbit as an animal model for intracavernous injection studies. The rabbit, having a penile structure rather similar to that of humans, offers the advantage of being a strain-specific, adequately sized, and easily controlled experimental animal. Using intracavernous injections of the two vasoactive drugs prostaglandin E1 (PGE1, 0.2-1.6 micrograms/kg) and papaverine (PAP, 0.25-1 mg/kg), which have been commonly used in the management of erectile dysfunction in man, increases intracavernous pressure (delta ICP) were induced. After intracavernous injection of PGE1, the maximal delta ICP ranged from 18 to 44 mmHg (mean 29.25 +/- 7.85 mmHg) with a duration of tumescence from 3.1 to 13.3 min (mean 8.61 +/- 3.71 min). Intracavernous injection of PAP also induced increases in ICP, with a maximal delta ICP ranging from 24 to 56 mmHg (mean 43.5 +/- 11.35 mmHg) and a duration of tumescence from 5.3 to 15 min (mean 10.25 +/- 3.39 min). The systemic blood pressures were unchanged after all intracavernous injections. In addition, administration of cAMP antagonist in combination with PGE1 inhibited the relaxing effects of PGE1 in a dose-dependent manner. Our results suggest that the effects of vasoactive drugs on the rabbit's corpus cavernosum are similar to those in humans; thus the rabbit model is a suitable alternative for further physiological and pharmacological studies of penile erection.
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PMID:The rabbit as an intracavernous injection study model. 896 38

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.
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PMID:Decreased penile erection in DOCA-salt and stroke prone-spontaneously hypertensive rats. 1178 42

In accordance with the data reporting the identification of nitric oxide synthase (NOS) and vasoactive intestinal polypeptide (VIP) positive nerve fibres in the trabecular meshwork of the corpus cavernosum, we suggest that nitric oxide (NO) and VIP may serve complementary physiological roles in penile erection. Therefore SIN-1 and VIP were administered alone and in combination in an in vivo rabbit model. All rabbits revealed basal pressure values of 5-8 cm H2O intracavernously. In the rabbits intracavernously (i.c.) injected with SIN-1 alone and VIP alone, no adequate erectile responses were observed. Whereas, in the group intracavernously injected with the combination of SIN-1+VIP, erectile responses with mean maximal intracavernous pressure (max. ICP) 52.8 (+/-13.2) cm H2O were noted. These pressure elevations do not statistically diverge (P>0.05) than the ones obtained in the control group administered i.c. injections of the combination of papaverine/phentolamine (mean max. ICP 51 (+/-14.73) cm H2O). Referring to our results, we conclude that the combined use of SIN-1+VIP could play an important role in the physiological treatment of erectile dysfunction.
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PMID:Intracavernous administration of SIN-1+VIP in an in vivo rabbit model for erectile function. 1189 77

Erectile dysfunction (ED) is frequently associated with injury to the cavernous nerve sustained during pelvic surgery. Functional recovery from cavernous nerve injury is generally incomplete and occurs over an extended time frame. We employed a therapeutic gene transfer approach with herpes simplex virus (HSV) vector expressing glial cell line-derived neurotrophic factor (GDNF). Rat cavernous nerve was injured bilaterally using a clamp and dry ice. For HSV-treated groups, 20 microl of purified vector stock was administered directly to and around the damaged nerve. Delivery of an HSV vector expressing both green fluorescent protein (GFP) and lacZ (HSV-LacZ) was used as a control. Intracavernous pressure along with systemic arterial pressure (ICP/AP) was measured 2 and 4 weeks after the nerve injury. Fluorogold (FG) was injected into the penile crus 7 days before killing to assess nerve survival. Approximately 60% of major pelvic ganglion (MPG) cells were GFP positive after viral administration. At 4 weeks after nerve injury, rats treated with HSV-GDNF exhibited significant recovery of ICP/AP compared with control vector or untreated groups. The HSV-GDNF group also yielded more FG-positive MPG cells than the control vector group. HSV vector-mediated delivery of GDNF presents a viable approach for the treatment of ED following cavernous nerve injury.
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PMID:Herpes simplex virus vector-mediated delivery of glial cell line-derived neurotrophic factor rescues erectile dysfunction following cavernous nerve injury. 1761 85

Liquid intraurethral prostaglandin E1 (PGE1) delivery system was developed using self-microemulsifying drug delivery system (SMEDDS). For this, pseudo-ternary phase diagrams were constructed and characterized. The viscosity of optimized formulation was increased gradually upon the addition of water and it was decreased from the water contents over 40%. With excessive mass of water, the present system transformed to a free flowing microemulsion. These results demonstrate that the present liquid PGE1 SMEDDS formulation might stay in the urethra as a viscous sol or gel state with contacting the moisture of urethra and easily eliminated by urination. Draize test and long-term stability study revealed that the present system would be safe and PGE1 would be stable for more than one year at 4 degrees C, respectively. In the feline animal model, SMEDDS formulation was as effective as PGE1 intracavernosal injections in terms of ICP (intracavernosal pressure), penile length increment, and erection sustaining time was more elongated than PGE1 injections. Therefore, SMEDDS was considered as a promising PGE1 intraurethral liquid formulation for erectile dysfunction treatment.
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PMID:Design and evaluation of prostaglandin E1 (PGE1) intraurethral liquid formulation employing self-microemulsifying drug delivery system (SMEDDS) for erectile dysfunction treatment. 1837 60

The venom of the spider Phoneutria nigriventer contains several toxins that have bioactivity in mammals and insects. Accidents involving humans are characterized by various symptoms including penile erection. Here we investigated the action of Tx2-6, a toxin purified from the P. nigriventer spider venom that causes priapism in rats and mice. Erectile function was evaluated through changes in intracavernosal pressure/mean arterial pressure ratio (ICP/MAP) during electrical stimulation of the major pelvic ganglion (MPG) of normotensive and deoxycorticosterone-acetate (DOCA)-salt hypertensive rats. Nitric oxide (NO) release was detected in cavernosum slices with fluorescent dye (DAF-FM) and confocal microscopy. The effect of Tx2-6 was also characterized after intracavernosal injection of a non-selective nitric oxide synthase (NOS) inhibitor, L-NAME. Subcutaneous or intravenous injection of Tx2-6 potentiated the elevation of ICP/MAP induced by ganglionic stimulation. L-NAME inhibited penile erection and treatment with Tx2-6 was unable to reverse this inhibition. Tx2-6 treatment induced a significant increase of NO release in cavernosum tissue. Attenuated erectile function of DOCA-salt hypertensive rats was fully restored after toxin injection. Tx2-6 enhanced erectile function in normotensive and DOCA-salt hypertensive rats, via the NO pathway. Our studies suggest that Tx2-6 could be important for development of new pharmacological agents for treatment of erectile dysfunction.
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PMID:Tx2-6 toxin of the Phoneutria nigriventer spider potentiates rat erectile function. 1839 97

Combining the centrally acting drug yohimbine with the peripheral conditioner sildenafil might be an approach to erectile dysfunction cases in which sildenafil alone failed. This work aimed to investigate the effect of yohimbine on sildenafil-induced facilitation of erectile process. Erectile responses to electrical stimulation of the cavernous nerve in anesthetized male rats were recorded. Intracavernosal pressure/systemic arterial pressure (ICP/SAP) was calculated, 1 and 5 min after intravenous administration of sildenafil, yohimbine or a combination of both. Changes in sexual arousal and copulatory performance indices were compared before and after these injections using behavioral mating experiments. It was shown that systemic administration of sildenafil produced a significant increase in ICP/SAP than control at doses >or=10 micromol kg(-1). Yohimbine alone failed to potentiate erectile responses but yohimbine (1 micromol kg(-1)) significantly potentiated the effect of sildenafil 1-10 micromol kg(-1) and 1 mmol kg(-1), 1 and 5 min after injection. Potentiation of ICP/SAP induced by their combination was greater than the sum of the effects of the corresponding doses of either drug at the same time interval. A nonsignificant additional decrease in SAP than sildenafil-induced was observed if administered with yohimbine. Addition of sildenafil to yohimbine significantly enhanced the effect of the latter on intromission frequency, intercopulatory interval and the number of ejaculations per session. It is concluded that yohimbine may enhance and prolong the effect of sildenafil on erectile process without additional hypotension. Sildenafil may enhance the central effects of yohimbine on erection; it amplifies the effect of yohimbine on male copulatory performance but not on sexual motivation. The potential beneficial effect of the combination was found to be more pronounced on the central component than on the peripheral component of the erectile process.
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PMID:Yohimbine enhances the effect of sildenafil on erectile process in rats. 1841 93

Neurturin (NTN), a member of glial cell line-derived neurotrophic factor (GDNF) family, is known as an important neurotrophic factor for penis-projecting neurons. We recently demonstrated significant protection from erectile dysfunction (ED) following a replication-defective herpes simplex virus (HSV) vector-mediated GDNF delivery to the injured cavernous nerve. Herein, we applied HSV vector-mediated delivery of NTN to this ED model. Rat cavernous nerve was injured bilaterally using a clamp and dry ice. For HSV-treated groups, 20 microl of vector stock was administered directly to the damaged nerve. Delivery of an HSV vector expressing both green fluorescent protein and lacZ (HSV-LacZ) was used as a control. Intracavernous pressure along with systemic arterial pressure (ICP/AP) was measured 2 and 4 weeks after the nerve injury. Fluorogold (FG) was injected into the penile crus 7 days before being killed to assess neuronal survival. Four weeks after nerve injury, rats treated with HSV-NTN exhibited significantly higher ICP/AP compared with untreated or control vector-treated groups. The HSV-NTN group had more FG-positive major pelvic ganglion neurons than the control group following injury. HSV vector-mediated delivery of NTN could be a viable approach for the improvement of ED following cavernous nerve injury.
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PMID:Herpes simplex virus vector-mediated delivery of neurturin rescues erectile dysfunction of cavernous nerve injury. 1866 42

Erectile dysfunction (ED) is a major complication of diabetes mellitus (DM). This study investigates the relationship between ED and the downregulation of constitutive nitric oxide synthase (cNOS) in the corpus cavernosum (CC) of diabetic rats. It also examines the effects of udenafil, a phosphodiesterase type 5 (PDE5) inhibitor, on ED and cNOS expression levels. After 16 weeks of daily oral treatment with udenafil in diabetic rats, the intracavernous pressure/mean arterial pressure (ICP/MAP) ratio was recorded to measure erectile function, and cNOS expression was measured using reverse transcriptase (RT)-PCR and immunoblots. Although the ICP/MAP ratio and the expression levels of endothelial NOS (eNOS) and neuronal NOS (nNOS) in the CC were markedly decreased in diabetic rats, long-term udenafil treatment improved the erectile function and increased cNOS expression compared with diabetic controls. These findings suggest that ED in DM is closely related to decreased cNOS expression in the CC and that udenafil has the ability to compensate for this pathological change by modulating cNOS expression. Udenafil also has an inhibitory role in cGMP (cyclic guanosine monophosphate) degradation.
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PMID:Increased expression of the nitric oxide synthase gene and protein in corpus cavernosum by repeated dosing of udenafil in a rat model of chemical diabetogenesis. 1946 35

Erectile dysfunction (ED) is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid II. This study investigates the effects of icarisid II on diabetic rats with ED and its potential mechanism via the assessment of advanced glycosylation end products (AGEs), autophagy, mTOR and the NO-cGMP pathway. Icarisid II was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid II group, rats were administered icarisid II intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure (ICP/MAP). AGE concentrations, nitric oxide synthase (NOS) activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 localisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid II increased ICP/MAP values, the smooth muscle cell (SMC) growth curve, S phase and SMC/collagen fibril (SMC/CF) proportions and decreased Beclin 1 (P<0.05). Icarisid II significantly increased the proliferative index and p-p70S6K(Thr389) levels and decreased the numbers of autophagosomes and the levels of LC3-II (P<0.01). Icarisid II decreased AGE concentrations and increased cGMP concentration, NOS activity (P<0.05) and cNOS levels (P<0.01) in the diabetic ED group. Therefore, Icarisid II constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.
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PMID:Effect of icarisid II on diabetic rats with erectile dysfunction and its potential mechanism via assessment of AGEs, autophagy, mTOR and the NO-cGMP pathway. 2272 70


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