Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although nitric oxide (NO) is recognized as the primary vasodilator derived from vascular endothelium in regulating the vascular tone, another factor, i.e. the endothelium-derived hyperpolarizing factor (EDHF), has recently gained much attention and has been demonstrated to participate in vasodilatation in various blood vessels from different species, despite its unidentified nature. Most of the studies were conducted in animals and the knowledge of this factor in the human vasculature is relatively limited. This review attempts to address the relevance of EDHF-mediated function in humans with the possible identity of EDHF and mechanisms involved. We consider the human vasculature where EDHF involvement has been documented including the systemic, coronary, and visceral (gastrointestinal, renal and reproductive) circulation. In these vascular systems, EDHF plays a role under physiological conditions either as another mechanism or as the "back-up" for NO. Furthermore, the contribution of EDHF changes under certain physiological conditions, such as ageing and pregnancy. In addition, altered EDHF function has been suggested in various pathological conditions including heart diseases, atherosclerosis, hypertension, diabetes, eclampsia, glaucoma, chronic renal failure, erectile dysfunction and ischemia-reperfusion period during open heart surgery. Pharmacological agents such as potassium channel openers or cytochrome P450 metabolites have been used to either protect or recover EDHF-dependent mechanisms. To further develop new therapeutic strategies that target EDHF, a better understanding is essential with regard to the function of EDHF under pathophysiological conditions in humans. Furthermore, the interaction between NO and EDHF as well as their relative contributions in various conditions are critical.
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PMID:The significance of endothelium-derived hyperpolarizing factor in the human circulation. 1726 16

Ischaemia-reperfusion damage induced by torsion/detorsion of the testicles may be a causative factor leading to erectile dysfunction through oxidative stress-dependent changes in the responses of the penile bulb, an erectile tissue of the penis. We aimed at investigating the effects of unilateral testicular torsion/detorsion (2 or 24 hr) treatment on relaxations induced by electrical field stimulation and sodium nitroprusside in rat isolated penile bulb. Male Sprague-Dawley rats used in the study were divided into two groups. The treatment group was subjected to unilateral torsion followed by detorsion for 2 or 24 hr, while the control group underwent only sham operation. For in vitro organ bath experiments, penile bulbs were isolated and responses to relaxant agents and electrical field stimulation (70 V, 1 msec., 0.5-8 Hz, 5 sec.) were recorded on a computer-based data acquisition system via a force displacement transducer. In tissues precontracted with phenylephrine (3 x 10(-6 )M), relaxations induced by electrical field stimulation were not significantly different before and after 2 or 24 hr of detorsion. Similarly sodium nitroprusside- (10(-8)-3 x 10(-6 )M) and papaverine-induced (10(-7)-10(-4 )M) relaxations were also found unchanged in the detorsion group compared to control. In conclusion, spermatic cord torsion did not lead to impairment in nitric oxide-mediated relaxant responses of the rat isolated penile bulb.
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PMID:Torsion/detorsion of the testis does not modify responses to nitric oxide in rat isolated penile bulb. 1765 13

Despite the proven clinical efficacy of phosphodiesterase inhibitors in the treatment of erectile dysfunction (ED), some patients do not respond to the medication. By means of nailfold capillary microscopy in patients with concomitant coronary artery disease (CAD) and ED, it was evaluated whether the extent of microvascular dysregulation predicts the responsiveness to tadalafil (TAD) in terms of erectile function. The ED of each patient was assessed by the International Index of Erectile Function (IIEF). Patients presenting both, documented CAD and ED, showed a significantly reduced capillary red blood cell velocity (v(RBC)) at rest and after 3 min of ischemia compared with age-matched controls. At 2 h after intake of 20 mg of TAD, a significant increase of v(RBC) at rest as well as during postischemic hyperemia was found. Patients who reported no improvement of their ED after the use of TAD demonstrated no changes in the duration of postischemic (DpH) hyperemia, or even a reduction of the DpH. The majority of the patients, who reported at least one successful sexual intercourse due to TAD, had a prolongation of DpH. We conclude that assessment of microvascular regulation by nailfold capillary microscopy can predict the probability of a treatment failure with phosphodiesterase inhibitors in patients with ED. Moreover, as endothelial dysfunction is the common underlying pathophysiological process of ED and cardiovascular diseases, the test may help to identify patients at risk for the development of atherosclerosis and following cardiovascular events.
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PMID:Cutaneous microcirculatory function predicts the responsiveness to tadalafil in patients with erectile dysfunction and coronary artery disease. 1770 23

Little has been published about sexual function in chronic heart failure (CHF) and knowledge among clinicians in this regard is sparse. To review data regarding sexual function and dysfunction in patients with CHF, 2 of the authors (S.A.M. and P.A.U.) independently conducted a literature search using the MEDLINE database. English-language articles and cited bibliographies published between January 1996 and November 2006 were reviewed. Search terms included heart failure or CHF or ventricular dysfunction or heart disease in conjunction with sexual activity, erectile dysfunction, impotence, or sex. Articles were selected for inclusion if they had a primary focus on CHF and sexual function or dysfunction. Critical reviews of the literature, observational studies using self-reported patient surveys, and prospective, blinded, randomized, placebo-controlled trials were included. Articles were not excluded on the basis of patient sample size but were excluded if the article concerned a broad aspect of cardiovascular disease rather than CHF. When properly screened and treated, most patients with CHF can safely engage in sexual activity and be treated for erectile dysfunction with sildenafil, provided that they do not have active ischemia and do not require treatment with nitrates. Clinicians should know the physiological requirements of sexual activity and the impact CHF has on sexual performance. Fear of a cardiac event during intercourse can interfere with patients' ability to perform and enjoy sex, and so it is important that the physician be able to counsel patients with CHF about sexual activity.
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PMID:Sexual activity and chronic heart failure. 1790 27

Sildenafil (Viagra), a phosphodiesterase type-5 inhibitor used in treatment of male erectile dysfunction and pulmonary hypertension can induce cardioprotection through opening of mitochondrial ATP-sensitive K(+) channels (mitoK(ATP)). Recent studies suggest that activation of mitochondrial Ca(2+)-activated K(+) channels (mitoK(Ca)) also has anti-ischemic effects. However, the relative role of mitoK(Ca) and mitoK(ATP) in sildenafil-induced cardioprotection remains unknown. In the present study, adult male ICR mice were pretreated with sildenafil (0.71 mg/kg, i.p.) 24 h prior to 20 min of global ischemia followed by 30 min of reperfusion in Langendorff mode. Paxilline (blocker of K(Ca)) or 5-hydroxydecanoic acid (5-HD; blocker of mitoK(ATP)) was administered either 30 min before sildenafil or 10 min prior to ischemia. Treatment with sildenafil reduced infarct size, which was abolished by either paxilline or 5-HD. Furthermore, in vivo gene knockdown of beta1 subunit of K(Ca) (K(Ca)-beta1) using small interfering RNA (siRNA) administered 48 h before sildenafil injection blocked the infarct limiting effect of sildenafil. The protective effect of sildenafil was preserved in mice treated with non-target siRNA. Western blots demonstrated selective protein expression of K(Ca)-beta1 in cardiac mitochondria and the gene knockdown effect of siRNA on K(Ca)-beta1. The level of K(Ca)-beta1 protein was not upregulated following treatment with sildenafil. We conclude that both mitoK(Ca) and mitoK(ATP) play a critical role in triggering and mediating sildenafil-induced delayed cardioprotection. The results suggest that activation of mitoK(Ca) and mitoK(ATP) are crucial for maintaining mitochondrial homeostasis and reducing cell death in sildenafil-induced preconditioning against ischemia-reperfusion injury.
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PMID:Essential role of mitochondrial Ca2+-activated and ATP-sensitive K+ channels in sildenafil-induced late cardioprotection. 1802 98

Phosphodiesterase type 5A (PDE5A) selectively hydrolyzes cyclic GMP. Inhibitors of PDE5A such as sildenafil are widely used to treat erectile dysfunction, but growing evidence supports important roles for the enzyme in both the vasculature and heart. In disorders such as cardiac failure, PDE5A upregulation may contribute to a decline in cGMP and protein kinase G signaling, exacerbating dysfunction. PDE5A plays an important role in the pulmonary vasculature where its inhibition benefits patients with pulmonary hypertension. In the heart, PDE5A signaling appears compartmentalized, and its inhibition is cardioprotective against ischemia-reperfusion and antracycline toxicity, blunts acute adrenergic contractile stimulation, and can suppress chronic hypertrophy and dysfunction attributable to pressure-overload. In this review, we discuss the molecular biology, pharmacology, and physiology of PDE5A, mechanisms of vascular and cardiac regulation, and recent evidence supporting the utility of selective PDE5A inhibition for the treatment of cardiovascular disorders.
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PMID:Phosphodiesterase type 5: expanding roles in cardiovascular regulation. 1804 25

The present paper serves as a review of the associations between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED), with a focus on common and combined pathways for treatment. LUTS and ED are common conditions seen in general urologic practice. Research has started to establish epidemiologic and pathophysiologic links between the two conditions and a strong association confirmed across multiple studies. Men seeking care for one condition should always be interviewed for complaints of the other condition. Proposed common pathways include alpha-1 adrenergic receptor imbalance, Rho-kinase overactivity, endothelial cell dysfunction and atherosclerosis-induced ischemia. Medical therapy has replaced surgery as the first-line treatment for LUTS in most patients, with the incorporation of alpha-adrenergic receptor antagonists (alpha-ARAs) and 5-alpha-reductase inhibitors (5-ARIs) into everyday practice. Treatment with alpha-ARAs contributes to some improvement in ED, whereas use of 5-ARIs results in worsened sexual function in some patients. Phosphodiesterase-5 (PDE-5) inhibitors have revolutionized the treatment of ED with a simple oral regimen, and new insights demonstrate a benefit of combined use of PDE-5 inhibitors and alpha-ARAs. The mechanisms of action of these medications support these observed benefits, and they are being studied in the basic science and clinical settings. In addition, novel mechanisms for therapy have been proposed based on clinical and research observations. The minimally invasive and surgical treatments for LUTS are known to have adverse effects on ejaculatory function, while their effects on erectile function are still debated. Much remains to be investigated, but it is clear that the associations between LUTS and ED lay the foundation for future therapies and possible preventative strategies.
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PMID:Common approach to managing lower urinary tract symptoms and erectile dysfunction. 1808 43

Between March 1976 and December 2004, 1690 consecutive allogenic living donor renal transplants were carried out at Mansoura, Egypt. We herewith report on 1600 transplants that had a minimum follow-up period of one year. The overall graft survival rates were 76% and 52% at five and 10-years respectively. The corresponding patient survival rates were respectively 86% and 71%. The projected half-life was 10.7 years for grafts and 18.2 years for patients. Predictors for graft outcome were classified as pre-transplant variables, technical factors or post-transplant predictors. Among the long list of these variables, factors that had a significant impact on outcome by univariate analysis included donor's and recipient's age, donor-recipient consanguinity, HLA-A, cytomegalovirus (CMV) and hepatitis C virus (HCV) markers, ischemia time, primary immunosuppression, ad juvant therapy, total steroid dose within the first three months, number of acute rejection episodes, time to onset of diuresis, hypertension post-transplant, serum creatinine at one year and at last follow-up besides chronic rejection. Only five factors sustained their significance by multivariate analysis: they included recipient's age, primary immunosuppression, post-transplant hypertension and serum creatinine at one year and last follow-up. Some specific complications encountered among the recipients such as hemolytic anemia, post-transplant diabetes mellitus, bone complications, malignancy, erectile dysfunction and surgical complications are discussed. In conclusion, we hope to start the cadaveric donor transplant program soon in our unit. Also, the ambition concerning the transplantation field in the new millennium is to overcome xenotransplantation barriers and to induce immunologic tolerance with neither rejection nor immunosuppression.
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PMID:Living donor renal transplantation, 1976 - 2003: the mansoura experience. 1820 12

Evidence indicates that nitric oxide (NO) deficiency contributes to micturition disorders, especially in the afferent pathway and erectile dysfunction (ED). Two possible causes of NO deficiency are substrate (L-arginine) limitation and increased levels of endogenous inhibitors of NO synthase (particularly asymmetric dimethylarginine: ADMA) in plasma and tissues. Elevated tissues of ADMA and N(G)-monomethyl-L-arginine (L-NMMA) have been reported to be associated with impaired NO-mediated urethral, trigonal and cavernosal relaxations by pelvic ischemia. Also, plasma ADMA may help to identify underlying cardiovascular disease in men with ED. Decreased l-arginine availability to NO synthase is due to the shunting of L-arginine into other pathways such as arginase. Interaction between NO synthase and arginase has been reported to be involved in NO-mediated urethral and prostatic relaxations. Also, increased arginase activity in cavernosal tissues likely contributes to the ED that accompanies diabetes mellitus and aging. Therefore, arginase inhibition has been reported to enhance the NO-dependent physiological process for erectile function.
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PMID:Significance of nitric oxide and its modulation mechanisms by endogenous nitric oxide synthase inhibitors and arginase in the micturition disorders and erectile dysfunction. 1826 46

Coil embolization of the internal iliac artery (IIA) is used to extend the application of endovascular aneurysm repair (EVAR) in cases of challenging iliac anatomy. Pelvic ischemia is a complication of the technique, but reports vary as to the rate and severity. This study reports our experience with IIA embolization and compares the results to those of other published series. The vascular unit database of the Leicester Royal Infirmary was used to identify patients who had undergone IIA coil embolization prior to EVAR. Data were collected from hospital case notes and by telephone interviews. Thirty-eight patients were identified; 29 of these were contactable by telephone. A literature search was performed for other studies of IIA embolization and the results were pooled. In this series buttock claudication occurred in 55% (16 of 29 patients) overall: in 52% of unilateral embolizations (11 of 21) and 63% of bilateral embolizations (5 of 8). New erectile dysfunction occurred in 46% (6 of 13 patients) overall: in 38% of unilateral embolizations (3 of 8) and 60% of bilateral embolizations (3 of 5). The literature review identified 18 relevant studies. The results were pooled with our results, to give 634 patients in total. Buttock claudication occurred in 28% overall (178 of 634 patients): in 31% of unilateral embolizations (99 of 322) and 35% of bilateral embolizations (34 of 98) (p = 0.46, Fisher's exact test). New erectile dysfunction occurred in 17% overall (27 of 159 patients): in 17% of unilateral embolizations (16 of 97) and 24% of bilateral embolizations (9 of 38) (p = 0.33). We conclude that buttock claudication and erectile dysfunction are frequent complications of IIA embolization and patients should be counseled accordingly.
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PMID:Buttock claudication and erectile dysfunction after internal iliac artery embolization in patients prior to endovascular aortic aneurysm repair. 1833 12


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