What question did this study set out to answer?

To determine whether endothelium-derived hyperpolarizing factor produces nitric oxide- and prostacyclin-independent vasodilation in resistance vessels of wild-type and endothelial nitric oxide synthase knockout mice.

August 15, 2000Proceedings of the National Academy of SciencesOpen Access

An endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium-dependent vasodilator in resistance vessels of wild-type and endothelial NO synthase knockout mice

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Population

Wild-type (WT) and endothelial NO synthase knockout (eNOS -/-) mice

Comparison

Endothelium-dependent agonists and various… vs WT vs eNOS -/- mice, and responses with vs…

Design

Preclinical

Authors

RBRalf P. BrandesVascular / Pulmonary Vascular FSFriedrich-Hubertus Schmitz-WinnenthalHeidelberg University MFMichel FélétouServier (France)

Discussion

Member takes

Implication

Does not alter human vasodilator therapy; leaves open whether gap junction-dependent EDHF predominates in clinical resistance vessels.

Key Points

To determine whether endothelium-derived hyperpolarizing factor produces nitric oxide- and prostacyclin-independent vasodilation in resistance vessels of wild-type and endothelial nitric oxide synthase knockout mice.
Measured in vivo mean arterial pressure changes in response to bradykinin in wild-type and eNOS -/- mice following treatment with L-NAME and diclofenac.
Evaluated in vitro vasodilatory responses to acetylcholine and bradykinin in saline-perfused hindlimbs of wild-type and eNOS -/- mice exposed to nitric oxide and cyclooxygenase inhibitors.
Assessed pharmacological inhibition of potassium channels (apamin and charybdotoxin), gap junctions (18alpha-glycyrrhetinic acid, octanol, heptanol), and cytochrome P450 enzymes.
Bradykinin induced dose-dependent reductions in mean arterial pressure in vivo that showed no difference between wild-type and eNOS -/- mice and remained completely unaffected by L-NAME and diclofenac.
Hindlimb perfusion demonstrated strong NO- and prostacyclin-independent vasodilation to acetylcholine and bradykinin that was abolished by elevated potassium chloride, apamin plus charybdotoxin, and gap junction inhibitors.
Inhibition of cytochrome P450 enzymes, soluble guanylyl cyclase, or adenosine receptors failed to alter the hyperpolarizing factor-mediated vasodilation.

Structured PICO

Population

Wild-type (WT) and endothelial NO synthase knockout (eNOS -/-) mice

Intervention

Endothelium-dependent agonists (bradykinin, acetylcholine) and various inhibitors (N(omega)-nitro-l-arginine methyl ester, diclofenac, KCl, apamin, charybdotoxin, gap junction inhibitors, CB-1 cannabinoid-receptor agonists)

Comparator

WT vs eNOS -/- mice, and responses with vs without inhibitors

Outcome

Vasodilator responses (mean arterial pressure in vivo and hindlimb vasodilation in vitro)surrogate

This study demonstrates that an EDHF-like factor, distinct from NO and prostacyclin and dependent on gap junctions, is a major endothelium-dependent vasodilator in murine resistance vessels.

Cite This Study

Brandes et al. (2000) studied this question.

synapsesocial.com/papers/6a706c5e22b3175134db50cc https://doi.org/10.1073/pnas.97.17.9747

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An endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium-dependent vasodilator in resistance vessels of wild-type and endothelial NO synthase knockout mice

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

An endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium-dependent vasodilator in resistance vessels of wild-type and endothelial NO synthase knockout mice

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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