Landiolol hydrochloride ameliorates acute lung injury in a rat model of early sepsis through the suppression of elevated levels of pulmonary endothelin-1.

Among the dysfunctions and pathologies associated with sepsis, the underlying molecular mechanisms of sepsis-induced acute lung injury (ALI) are poorly understood. Endothelin (ET)-1, a potent vasoconstrictor and pro-inflammatory peptide, is known to be involved in the pathogenesis of ALI in a rat model of sepsis. Here, we investigated whether landiolol hydrochloride, an ultra-short-acting ß-blocker, plays a crucial role in ameliorating and attenuating LPS-induced ALI through modulation of the ET-1 system. Male Wistar rats at 8weeks of age were administered with either saline or lipopolysaccharide (LPS) for three hours (3h) and some of the LPS-administered rats were continuously treated with landiolol for 3h. ALI was induced by LPS, including levels of both circulatory and pulmonary TNF-α and IL-6 but [PaO2] was significantly decreased. LPS also induced a significant increase in levels of pulmonary ET-1 and ET-A receptor, but levels of ET-B receptor, which has vasodilating effects, were remarkably diminished. Further, LPS administration upregulated the pulmonary expression of HIF-1α. Finally, the treatment of LPS-administered rats with landiolol for 3h ameliorated and prevented ALI, normalized the altered levels of pulmonary ET-1 and ET-A receptors. Landiolol also induced significant down-regulation of ET-B receptor in lung tissues in the early hours (phase) of sepsis. However, Landiolol treatment had no effect on the up-regulated inflammatory mediators (TNF-α, IL-6) in both plasma and lung tissues during sepsis, and expression of pulmonary HIF-1α also remained unchanged after landiolol treatment. Collectively, these data led us to conclude that landiolol may ameliorate sepsis-induced ALI via the pulmonary ET system.

Higher circulatory level of endothelin-1 in hypertensive subjects screened through a cross-sectional study of rural Bangladeshi women.

Endothelin-1 (ET-1) is a potential marker of the endothelial dysfunction, which has been shown to be elevated in hypertensive subjects. No previous study has investigated the circulatory level of ET-1 and hypertension in a South Asian country. The present study assessed the circulating levels of ET-1 in subjects with or without hypertension and further examined the association of ET-1 with clinical and metabolic parameters. A total of 2543 rural Bangladeshi women with a mean age of 44.5 years were studied using a cross-sectional survey. Multiple regressions were used to examine the association between the circulatory ET-1 levels and hypertension. The prevalence of hypertension was 29.3%. The ET-1 levels were significantly higher in the hypertensive (mean 3.08 pg ml(-1), s.e. (0.19)) than in the non-hypertensive subjects (mean 2.01 pg ml(-1), s.e. (0.03)) (P = 0.001). After adjusting for age, the ET-1 level had significant positive associations with the diastolic blood pressure (P = 0.002), systolic blood pressure (P = 0.001), mean arterial pressure (P = 0.002) and fasting blood glucose (P = 0.002). In a tertile analysis, we found that hypertension in the subjects was significantly increased as the levels of ET-1 increased (P for the trend = 0.001). In a stepwise multiple regression analysis, after adjusting for age and all other potential variables, we found that the mean arterial pressure and the fasting plasma levels have significant associations with the ET-1 level. The present study demonstrates that there is a higher concentration of ET-1 among the hypertensive subjects in an apparently healthy population of Bangladeshi rural women. The relationship between ET-1 and hypertension requires further investigation to define the clinical utility and predictive value of serum ET-1 levels for hypertension for a South Asian population.