Endothelin-1 receptor blockade induces upregulation of renin-angiotensin-aldosterone system expression in terms of blood pressure regulation

Abstract

Objective.To compare the level of expression of the renin-angiotensin-aldosterone system (RAAS) in mice with or without the endothelin-1 receptor antagonist bosentan and to examine the potential value in blood pressure regulation. Materials and methods. Bosentan (10 mg/kg/d) and placebo were given to two groups of male C57BL/6 mice (n=5) from ages 6 to 12 weeks. The mRNAs of liver, kidney and lung were isolated for Northern blot analysis. A further 15 male C57BL/6 mice were divided into three groups (n=5): mice in group A were given the angiotensin II type 1 receptor blocker valsartan (10 mg/kg/d); mice in group B were given bosentan (10 mg/kg/d); and mice in group C were given both valsartan and bosentan (10 mg/ kg/d for each drug). All mice were administered the drugs from 6 to 12 weeks of age and had their systolic blood pressure (SBP) measured at the end of the drug treatments.Results. Northern blot analysis demonstrated that the expression levels of angiotensinogen in liver (p=0.0126), renin in kidney (p=0.002), and angiotensin-converting enzyme in lung (p=0.0041) were upregulated in mice treated with bosentan. No difference in SBP was found among the groups before drug administration. Six weeks after monotherapy with valsartan, SBP was slightly lowered (126±2 vs. 122±3 mmHg, p=0.0381). Monotherapy with bosentan also had a small effect on SBP (126±2 vs. 122±3 mmHg, p=0.0381), whereas dual blockade with valsartan and bosentan significantly lowered SBP (127±3 vs. 103±3 mmHg, p<0.001). Conclusions. We conclude that RAAS components are upregulated under endothelin blockade. Dual blockade of the RAAS and endothelin system is beneficial for blood pressure control.

Deterioration of endothelial function and carotid intima-media thickness in Tibetan male adolescents exposed to second-hand smoke

“…ET-1 was first isolated from porcine aortic endothelial cells by Yanagisawa et al 24 Since its discovery, ET-1 has been demonstrated as one of the most potent known vasoconstrictors. 25 ET-1 release causes massive vasoconstriction, increased blood pressure and, in turn, induced endothelial dysfunction. ET-1 is synthesized by endothelial cells and smooth muscle cells, as well as by macrophages, cardiomyocytes, neurons, and renal medulla cells.…”

RETRACTED: Bosentan attenuates cardiac fibrosis in diabetic mice without affecting blood glucose

“…Studies found that the diabetic complications are partly consequences of an activated ET system, which could lead to myocardial and vascular dysfunction. 16 Unfortunately, few study attempts to clarify the potent protective effect of bosentan, a non-selective ETa and ETb receptor antagonist, 17 on diabetic cardiovascular complications, especially myocardial fibrosis. There has been increasing research interest in understanding the impact of diabetes on cardiovascular disease, 18,19 and myocardial fibrosis is identified as an incurable complication.…”

Effect of hypertonic sodium chloride hydroxyethyl starch 40 on ET, TXB2, 6-keto-PGF1α, and ANP of preeclampsia in caesarean section

“…Thus, HSH may have inhibited angiotensin II (Ang II), which stimulates ET secretion from cultured bovine endothelial cells via a receptor-mediated process [14][15][16]. Moreover, HSH may have enhanced ANP secretion, which interacts with ET secretion from the endothelium through the renin-angiotensin system [17,18]. Compared with Ringer-Locke liquor, HSH40, which inhibits ET secretion, may improve the symptoms of preeclampsia.…”