What question did this study set out to answer?

To determine the respective roles of endothelin, angiotensin II, and elevated blood pressure in mediating cardiovascular and renal end-organ damage in spontaneously hypertensive rats.

September 1, 1996Hypertension

Endothelin Antagonism in End-Organ Damage of Spontaneously Hypertensive Rats

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Population

Spontaneously hypertensive rats (SHR) and normotensive Wistar rats

Comparison

Bosentan, enalapril, or mibefradil for 10 weeks vs Untreated spontaneously hypertensive rats and…

Design

Preclinical

Follow-up

10 weeks

Authors

HKHabib KaramRoche (Switzerland)DHDidier HeudesUniversité Claude Bernard Lyon 1 PBPatrick BrunevalHeart Failure & Transplant

Discussion

Member takes

Implication

Endothelin antagonism may confer BP-independent renal and remodeling benefits in hypertensive rat models; hypothesis-generating and should not change practice.

Key Points

To determine the respective roles of endothelin, angiotensin II, and elevated blood pressure in mediating cardiovascular and renal end-organ damage in spontaneously hypertensive rats.
Spontaneously hypertensive rats were treated for 10 weeks with the dual endothelin receptor antagonist bosentan (100 mg/kg per day), the ACE inhibitor enalapril (10 mg/kg per day), or the calcium antagonist mibefradil (20 mg/kg per day), compared to untreated hypertensive and normotensive Wistar controls.
Outcomes measured included isolated heart maximal coronary blood flow, quantitative morphometry of cardiac hypertrophy and fibrosis, aortic medial thickness, and renal functional markers including proteinuria and urea and creatinine clearances.
Bosentan did not alter systemic blood pressure, yet it normalized renal function and urea/creatinine clearance while moderately reducing left ventricular hypertrophy and perivascular fibrosis.
Enalapril and mibefradil significantly lowered blood pressure, reduced left ventricular hypertrophy and aortic medial thickness, and improved coronary blood flow, but failed to improve creatinine clearance.

Structured PICO

Population

Spontaneously hypertensive rats (SHR) and normotensive Wistar rats

Intervention

Bosentan (100 mg/kg per day), enalapril (10 mg/kg per day), or mibefradil (20 mg/kg per day) for 10 weeks

Comparator

Untreated spontaneously hypertensive rats and untreated normotensive Wistar rats

Outcome

Cardiac hypertrophy and fibrosis, aortic medial thickness, extracellular matrix content, renal function (proteinuria, urea and creatinine clearances), and maximal coronary blood flowsurrogate

In spontaneously hypertensive rats, endothelin antagonism with bosentan improves renal function and cardiac remodeling independently of blood pressure reduction.

Cite This Study

Karam et al. (1996) studied this question.

synapsesocial.com/papers/6a70d822f44fa9f079de9186 https://doi.org/10.1161/01.hyp.28.3.379

Topics

Hypertension management

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Implication

Endothelin antagonism may confer BP-independent renal and remodeling benefits in hypertensive rat models; hypothesis-generating and should not change practice.

Endothelin Antagonism in End-Organ Damage of Spontaneously Hypertensive Rats

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Endothelin Antagonism in End-Organ Damage of Spontaneously Hypertensive Rats

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

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