Efficacy of tadalafil in chronic hypobaric hypoxia–induced pulmonary hypertension: possible mechanisms

Abstract

The present study was carried out to investigate the effects of long-acting phosphodiesterase five inhibitor, tadalafil, on pulmonary hypertension induced by chronic hypobaric hypoxia in rats. Adult Albino Wistar rats were exposed to 2 weeks of hypobaric hypoxia for 8 h daily and treated with tadalafil or tempol, a standard antioxidant agent. Right ventricular systolic pressure (RVSP) was taken as an index for pulmonary arterial pressure; malondialdehyde, reduced glutathione and superoxide dismutase were chosen as the markers of oxidative stress; serum tumour necrosis factor alpha (TNF-α) levels and inflammatory changes in lungs were assessed for inflammation. Chronic hypobaric hypoxia was found to induce pulmonary hypertension, as it significantly (P < 0.001) increased RVSP. Chronic hypobaric hypoxia also leads to an increase in oxidative stress as was evidenced by an increase in malondialdehyde levels (P < 0.001) and a significant decrease in (P < 0.001) reduced glutathione levels and superoxide dismutase activity. Chronic hypobaric hypoxia-induced inflammation was revealed by lung histology and increase in serum TNF-α levels. Tadalafil significantly prevented (P < 0.001) rise in hypobaric hypoxia-induced rise in RVSP. Tadalafil partially while tempol completely reversed hypobaric hypoxia-induced oxidative stress. Lung inflammation and serum TNF-α levels were significantly attenuated by both tadalafil and tempol. However, effect of tadalafil on inflammation was more marked than that of tempol. These data indicate that tadalafil possess antioxidant as well as antinflammatory action in addition to its vasodilatory property. All these three actions combined may have positive impact of tadalafil in the treatment of hypobaric hypoxia-induced pulmonary hypertension.

Role of posterior hypothalamus in hypobaric hypoxia induced pulmonary edema

“…In humans as well as experimental animals, RVSP is used often as an index of pulmonary artery pressure (Rashid et al, 2013). Thus, the results would indicate that the pulmonary artery pressure rose in rats exposed to hypobaric hypoxia.…”

“…The renal sympathetic nerve activity (RSNA) was used for quantifying sympathetic outflow as it has been reported that exposure to hypoxia produces changes in RSNA which are qualitatively similar to those in pulmonary sympathetic nerves (Shirai et al, 1995). Pulmonary hypertension was assessed by recording right ventricular systolic pressure (RVSP) (Rashid et al, 2013). For quantification of lung water, along with the wet weight dry weight ratio, the vascular permeability using Evans blue was determined also.…”

Superoxide Dismutase Mimetic, MnTE-2-PyP, Attenuates Chronic Hypoxia-Induced Pulmonary Hypertension, Pulmonary Vascular Remodeling, and Activation of the NALP3 Inflammasome

“…with other tested antioxidant strategies, including tempol and allopurinol (9,21,38,39). We are particularly interested in its role as an extracellular superoxide scavenger because of compounding evidence that support the critical role of extracellular oxidative stress and EC-SOD in oxidative pulmonary injury.…”

Tracing the nitrogen metabolites of glycine using 15 N-glycine and mass spectrometry

“…from glycine but from an intrinsic source. Noticeably, glutathione is one of the most important biomarker molecules for oxidative stress; [25][26][27] thus, this 15 N-glycine technique could be valuable for use in GSH metabolism studies.…”