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August 16, 1994Proceedings of the National Academy of SciencesOpen Access

SB 209670, a rationally designed potent nonpeptide endothelin receptor antagonist.

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Key result

SB 209670, a potent nonpeptide endothelin receptor antagonist, produced a 52% reduction in neointima formation following balloon angioplasty in rats.

Population

Preclinical models including cloned human ET receptor subtypes ETA and ETB, isolated vascular tissues…

Design

Preclinical

Authors

EOEliot H. OhlsteinHeart Failure & TransplantPNP NambiApollo HospitalsSDStephen A. DouglasUniversity of Minnesota

Discussion

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Implication

Requires human trials before clinical use; leaves open therapeutic potential of endothelin antagonism in hypertension and stroke.

Structured PICO

P
Population
Preclinical study evaluating the endothelin receptor antagonist SB 209670 in vitro and in male rat and gerbil models of hypertension, stroke, and angioplasty.
I
Intervention
SB 209670 (non-peptide endothelin receptor antagonist), administered intravenously or intraduodenally in vivo
O
Outcome
Inhibition of ET-1 binding to ETA and ETB receptors, inhibition of ET-1-mediated vasoconstriction, reduction in blood pressure, protection from ischemia-induced neuronal degeneration, and attenuation of neointima formationsurrogate

Main Result

Effect estimate: 52% reduction

p-value: p=<0.05

SB 209670 is a potent, rationally designed non-peptide endothelin receptor antagonist that demonstrates physiological efficacy in preclinical models of hypertension, stroke, and vascular injury.

Limitations

  • Preclinical animal models may not fully translate to human clinical outcomes

Cite This Study

Ohlstein et al. (1994) studied Preclinical models of cardiovascular disease and stroke. SB 209670 vs. Vehicle was evaluated on Neointima formation following balloon angioplasty (52% reduction, p=<0.05). SB 209670, a potent nonpeptide endothelin receptor antagonist, produced a 52% reduction in neointima formation following balloon angioplasty in rats.

synapsesocial.com/papers/6a6d4ade2163a0a01bc2cd22https://doi.org/10.1073/pnas.91.17.8052
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Molecular characterization and regulation of the human endothelin receptors.1993 · 154 citations
  2. 2Is endothelin involved in the pathogenesis of hypertension?1993 · 103 citations
  3. 3Endothelin‐1 modulates vascular smooth muscle structure and vasomotion: Implications in cardiovascular pathology1993 · 76 citations
  4. 4Endothelin Peptides and the Kidney1993 · 67 citations
  5. 5Endothelin-1 Promotes Neointima Formation After Balloon Angioplasty in the Rat1993 · 60 citations