Hemodynamic effects of sildenafil interaction with a nitric oxide donor compound in a dog model of acute pulmonary embolism

Dias‐Junior, Carlos A.; Tanus‐Santos, José Eduardo

doi:10.1016/j.lfs.2006.01.034

Cited by 42 publications

(27 citation statements)

References 23 publications

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“…4 In double stained specimens, eNOS was stained as an intracytoplasmic brown color and thin granular structure with DAB chromogen (thin arrows) and apoptotic cell was stained as rough and reddish color with AEC chromogen (bold arrows). a Sildenafil group; b Vardenafil group Pediatr Surg Int (2008) 24:205-211 209 degraded by PDEs [20]. Thus inhibiting PDEs will elevate NO level in tissues and according to our findings this mechanism probably proceeds with the increasing of tissue NOS levels.…”

Section: Discussionsupporting

confidence: 59%

“…PDE5 inhibitors, work to improve ED by preventing the breakdown of cyclic GMP, the substance that promotes relaxation of smooth muscle cells in vascular system [18]. Although the main indication of these drugs is ED, the effectiveness of sildenafil in hypertensive cardiomyopathy [19], pulmonary hypertension [20], and renal damage via NO pathway [21] have been reported previously. Recently, FDA approved sildenafil in the treatment of pulmonary arterial hypertension of any functional class [22].…”

Section: Discussionmentioning

confidence: 99%

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Effect of phospodiesterase 5 inhibitors on apoptosis and nitric oxide synthases in testis torsion: an experimental study

et al. 2007

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To investigate the effects of phosphodiesterase (PDE) 5 inhibitors, sildenafil citrate and vardenafil HCl, on testicular germ cell apoptosis and also on the expressions of eNOS and iNOS within the bilateral testis after a unilateral torsion in a rat model. Forty-eight Wistar Albino rats, weighing between 210 and 262 g, were housed in individual cages. The rats were randomly assigned into four main groups and each group received drugs. Saline, sildenafil citrate and vardenafil HCl were given to each for 1 month and the last received no drug. After 1 month, testicular torsion was created for 1 h of ischemia and the left testis was untwisted and replaced to the scrotum for 2 h of reperfusion. At the end of 3 h, contralateral and ipsilateral testes were removed for histopathologic and biochemical examinations. Under light microscopy; the histopathological patterns of the contralateral testes in all groups were not affected. Mean apoptotic cell, eNOS and iNOS levels were increased in saline study group. The rats treated with vardenafil and sildenafil (groups 2s and 3s) showed significantly increased apoptotic cell, eNOS and iNOS values in ipsilateral testis (P < 0.05). Sildenafil citrate and vardenafil HCl caused an exaggerated testicular apoptosis after IR injury in rats. Additionally these drugs increased the NOSs levels in the testicular tissue.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Effect of phospodiesterase 5 inhibitors on apoptosis and nitric oxide synthases in testis torsion: an experimental study

et al. 2007

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“…Although the main indication of PDE-5 inhibitors is ED, the effectiveness of sildenafil in hypertensive cardiomyopathy [15] , pulmonary hypertension [16] , and renal damage via the NO pathway [17] has been reported previously. The favorable effects of PDE-5 usage on several tissues and organs, such as in flap survival and trans- planted and other organs, have been recently reported [18][19][20] .…”

Section: Discussionmentioning

confidence: 88%

Effects of Vardenafil on Testicular Torsion/Detorsion Damage: An Experimental Study in Pigs

et al. 2010

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Purpose: To investigate the effects of vardenafil HCl on testicular germ cell apoptosis and the expressions of iNOS and eNOS within the bilateral testes after unilateral torsion/detorsion (T/D) in a pig model. Methods: 12 male pigs weighing 50–55 kg were divided randomly into three groups (n = 4). Sham operation and T/D was performed in groups 1 and 2, respectively. Group 3 underwent T/D and received vardenafil (0.4 mg/kg) orally 45 min before detorsion. The testes were left in torsion for 2 h. In all groups, both testes were removed 8 h after the operation for histopathological analysis. Results: Except for group 1, the histopathologic parameters of the ipsilateral testes were higher than in the contralateral testes, and this difference was statistically significant (p < 0.05). Testicular ischemia/reperfusion (I/R) (group 2) resulted in marked increases in germ cell apoptosis, iNOS and eNOS in the ischemic testes compared to the sham-operated group. The pigs treated with vardenafil (group 3) also showed significantly increased apoptotic cells, iNOS and eNOS levels compared to the sham-operated group. Conclusions: The results suggest that vardenafil HCl worsened histopathological changes related to oxidative stress in testicular injury and had no protective effect on testicular I/R injury in pigs.

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“…Another explanation would be related with the lower time spent to the PE-induced PH on other PE models (from 180 min to several hours) [27,28]. Anyway, if the activation of the inflammatory response with the release of vasoactive mediators and increase of oxidative stress play some role in the pathogenesis of PH associated with PE [21,29], levosimendan would also have the advantage of attenuating the PE-induced PH through mechanisms involving antioxidant effects [30,31].…”

Section: Discussionmentioning

confidence: 99%

“…We have not measured any oxidative stress parameters like plasma nitrite/ nitrate concentrations and plasma lipid peroxide concentrations to demonstrate the presence of an increase in oxidative stress after lung embolization in PE group. Although we employed a relatively short period to embolize the lungs, a significant increase in plasma nitrite/nitrate concentrations were observed after 60 min of lung embolization in a canine PE model [29]. We were careful to analyze several PA rings from different lobs of both lungs of each animal to obtain a representative sample beyond the final distribution of blood clots.…”

Section: Limitationsmentioning

confidence: 99%

Preferential Vasodilator Effects of Levosimendan in Resistance Pulmonary Arteries in a Rodent Pulmonary Embolism Model

Bedo

Grignola

2017

ICFJ

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IntroductionThe pulmonary vasculature consists of large, elastic, extraparenchymal conduit pulmonary arteries (CPA, order 1 to 2) that arise from the sixth aortic arch and small, muscular resistance intrapulmonary arteries (RPA, ≥ 4th order), that originate from the mesenchymal lung bud by capillary plexus expansion [1]. This subdivision is associated with different response to several stimuli. While CPA dilates or fails to constrict to hypoxia, RPA is responsible for hypoxic pulmonary vasoconstriction, control the regional distribution of blood flow and largely determine pulmonary vascular resistance. This functional difference mainly depends on the distribution of electrophysiologically distinct myocytes in CPAs and RPAs arteries [1,2].Levosimendan is a positive inotropic agent (by increasing the sensitivity of troponin C to calcium) with vasodilating properties (by lowering of intracellular free Ca++, opening of different potassium channels and the inhibition of phosphodiesterase type III), also termed inodilator [3,4]. There are several animals studies in different acute pulmonary hypertension (PH) models secondary to thromboxane A2 infusion [5], endotoxemia [6], acute pulmonary embolism (PE) [7,8], and hypoxia [9] and some clinical studies that demonstrated the vasodilator effect of levosimendan on the pulmonary circulation, restoring right ventricular-arterial coupling as it increased right ventricular contractility concomitantly [10,11]. Acute PE-induced PH results from two main mechanisms: HighlightsBackground

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Hemodynamic effects of sildenafil interaction with a nitric oxide donor compound in a dog model of acute pulmonary embolism

Cited by 42 publications

References 23 publications

Effect of phospodiesterase 5 inhibitors on apoptosis and nitric oxide synthases in testis torsion: an experimental study

Effect of phospodiesterase 5 inhibitors on apoptosis and nitric oxide synthases in testis torsion: an experimental study

Effects of Vardenafil on Testicular Torsion/Detorsion Damage: An Experimental Study in Pigs

Preferential Vasodilator Effects of Levosimendan in Resistance Pulmonary Arteries in a Rodent Pulmonary Embolism Model

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