What question did this study set out to answer?

To determine whether endothelin A/B receptor blockade with bosentan reduces angiotensin II-mediated cardiac and renal damage, inflammation, and tissue factor activation independently of blood pressure lowering.

August 1, 2000Hypertension

Effect of Bosentan on NF-κB, Inflammation, and Tissue Factor in Angiotensin II–Induced End-Organ Damage

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To determine whether endothelin A/B receptor blockade with bosentan reduces angiotensin II-mediated cardiac and renal damage, inflammation, and tissue factor activation independently of blood pressure lowering.
Treated double-transgenic rats (dTGR) expressing human renin and angiotensinogen genes with bosentan (100 mg/kg by gavage) or the blood pressure control hydralazine (80 mg/L in drinking water) after 4 weeks of age.
Monitored systolic blood pressure, mortality rate, 24-hour albuminuria, and cardiac hypertrophy up to 7 weeks of age against untreated dTGR and Sprague-Dawley controls.
Assessed cardiac and renal tissue for NF-κB and AP-1 activation, adhesion molecules (ICAM-1, VCAM-1), macrophage infiltration, and tissue factor expression.
Untreated dTGR had a 45% mortality rate (9 of 20) by week 7, which was reduced to 1 of 15 with bosentan and 4 of 15 with hydralazine.
Both bosentan and hydralazine reduced systolic blood pressure (untreated dTGR 203±8 vs control 111±2 mm Hg) and cardiac hypertrophy, but only bosentan lowered 24-hour albuminuria (untreated 67.1±8.6 vs control 0.3±0.06 mg/d) and renal damage.
Bosentan markedly suppressed NF-κB and AP-1 activation, reduced macrophage infiltration and ICAM-1 expression, and blunted vascular and macrophage tissue factor expression in heart and kidney compared to hydralazine.

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Implication

Experimental study demonstrates bosentan reduces renal injury and tissue factor in hypertensive transgenic rats, indicating blood pressure-independent protection via endothelin blockade.

Cite This Study

Müller et al. (2000) studied this question.

synapsesocial.com/papers/6a169ecc83b2be9fec6b45ba https://doi.org/10.1161/01.hyp.36.2.282

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Implication

Experimental study demonstrates bosentan reduces renal injury and tissue factor in hypertensive transgenic rats, indicating blood pressure-independent protection via endothelin blockade.

Effect of Bosentan on NF-κB, Inflammation, and Tissue Factor in Angiotensin II–Induced End-Organ Damage

Key Points

Discussion

Implication

Cite This Study

Effect of Bosentan on NF-κB, Inflammation, and Tissue Factor in Angiotensin II–Induced End-Organ Damage

Key Points

Discussion

Implication

Cite This Study

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