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.
Long-acting phosphodiesterase 5 (PDE5) inhibitor, tadalafil, was recently approved for the treatment of pulmonary hypertension. Apart from being a PDE5 inhibitor, tadalafil also possesses antioxidant activity. The aim of this study was to probe whether tadalafil has any beneficial effect over tempol owing to its antioxidant action in addition to PDE5 inhibitory activity. Albino Wistar rats were pretreated with tadalafil (10 mg/kg) or vehicle 2 h before hypoxic exposure, whereas tempol (20 mg/kg) was given 5 min before induction of hypoxia. Right ventricular systolic pressure (RVSP), mean arterial pressure (MAP), heart rate (HR), right ventricular contractility (RVdP/dtmax) and cardiac output (CO) were recorded while subjecting rats to acute hypoxia for 30 min. Lipid peroxidation and reduced glutathione were estimated in serum before and after hypoxia exposure. Tadalafil as well as tempol significantly prevented hypoxia-induced rise in RVSP (p < 0.001) and RVdP/dtmax (p < 0.05). Both tadalafil and tempol pretreatment partially prevented (p < 0.01) the rise in CO due to hypoxia. Tadalafil did not produce any significant change in MAP, whereas tempol led to a significant fall (p < 0.01) in MAP. Acute hypoxia increased the oxidative stress levels. Tadalafil pretreatment partially prevented hypoxia-induced oxidative stress, while tempol pretreatment completely prevented hypoxia-induced oxidative stress. Results suggest that tadalafil because of its antioxidant action in addition to PDE5 inhibitory activity is more appropriate for the prevention of hypoxic pulmonary hypertension than tempol. Tempol also produced undesirable systemic hypotension as side effect, which was not seen with tadalafil because of its pulmonary selective action.
Background: Obesity along with hypertension is the common risk factor for the development of cardiovascular disease. Leptin, an anti-obesity hormone, is currently considered to play a vital role in the development of hypertension in obesity. We aim to determine the leptin levels in hypertensive and normotensive participants and to find the correlation between leptin and hypertension in obese and non-obese hypertensive subjects. Material and methods: A total of 94 participants aged > 18 years of either gender were included in the study. The participants were divided into obese (n = 55) and non-obese (n = 39) groups with further subgroups based on presence or absence of hypertension. Height, weight and blood pressure were taken with standard methods. Leptin was determined using ELISA method and intra and inter-group comparisons were made. Results: The leptin levels were significantly higher in obese (p = 0.000), hypertensive (p = 0.048) and females (p = 0.001) compared to non-obese, normotensive and male participants. Furthermore, obese hypertensive participants were having higher leptin levels compared to obese normotensive participants but with no statistical significance (p = 0.14). Serum leptin levels positively correlated with serum LDL (p = 0.003), body mass index (BMI) (p = 0.000), serum uric acid (p = 0.034) and fasting plasma glucose (FPG) (p = 0.001). However, on correction for factors like BMI, and obesity, positive correlation persisted only for female gender (p = 0.048) and FPG (p = 0.029). Furthermore, BMI (p = 0.021) and FPG (p = 0.027) were found to be the independent risk factors for elevated leptin levels on multiple regression analysis. Conclusions: Our study concluded that serum leptin levels are higher in obesity and have a direct correlation with degree of obesity. However, our study does not support any direct correlation between serum leptin and hypertension.
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