What question did this study set out to answer?

To determine whether selective ET_A receptor antagonism provides greater antihypertensive efficacy than combined ET_A/ET_B receptor antagonism in conscious transgenic hypertensive rats.

December 1, 2000British Journal of PharmacologyOpen Access

Cardiovascular effects of endothelin‐1 and endothelin antagonists in conscious, hypertensive ((mRen‐2)27) rats

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Why the study?

Does selective ETA antagonism (SB 234551) exert a greater antihypertensive effect than non-selective ET antagonism (SB 209670) in conscious, hypertensive ((mRen-2)27) rats?

Key Points

To determine whether selective ET_A receptor antagonism provides greater antihypertensive efficacy than combined ET_A/ET_B receptor antagonism in conscious transgenic hypertensive rats.
Administered 50-hour continuous infusions of the nonselective antagonist SB 209670 or the selective ET_A antagonist SB 234551 in conscious, heterozygous, transgenic ((mRen-2)27) hypertensive rats.
Assessed chronic blood pressure changes and cardiovascular pressor and depressor responses to exogenous endothelin-1 challenges at intervals across the 50-hour period.
Both SB 209670 and SB 234551 produced sustained reductions in blood pressure across 50 hours of continuous infusion.
Selective ET_A blockade with SB 234551 did not produce a greater antihypertensive effect than SB 209670, even at 2 to 4 hours when SB 209670 abolished the depressor effects of endothelin-1.
Blood pressure reductions occurred even when the pressor responses to exogenous endothelin-1 were not significantly inhibited.

Structured PICO

Does selective ETA antagonism (SB 234551) exert a greater antihypertensive effect than non-selective ET antagonism (SB 209670) in conscious, hypertensive ((mRen-2)27) rats?

Population

Conscious, heterozygous, transgenic ((mRen-2)27) hypertensive rats

Intervention

SB 209670 (non-selective ET antagonist) and SB 234551 (selective ETA antagonist) infused for 50 hours

Comparator

Comparison between the two antagonists (SB 209670 vs SB 234551)

Outcome

Antihypertensive effects and responses to exogenous endothelin-1surrogate

Selective ETA antagonism does not provide a greater antihypertensive effect than non-selective ET antagonism in a transgenic rat model of hypertension.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

Challenges assumption of ETA-selective superiority in hypertension; leaves open translation from this rat model to patients.

Cite This Study

Gardiner et al. (2000) studied this question.

synapsesocial.com/papers/6a86affa3f44447e627cabdc https://doi.org/10.1038/sj.bjp.0703767

Topics

Hypertension management

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Cardiovascular effects of endothelin‐1 and endothelin antagonists in conscious, hypertensive ((mRen‐2)27) rats

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Topics

Cardiovascular effects of endothelin‐1 and endothelin antagonists in conscious, hypertensive ((mRen‐2)27) rats

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Topics

Also Consider