P-450 metabolites of arachidonic acid in the control of cardiovascular function.

  title={P-450 metabolites of arachidonic acid in the control of cardiovascular function.},
  author={Richard J Roman},
  journal={Physiological reviews},
  volume={82 1},
  • R. Roman
  • Published 2002
  • Biology, Medicine
  • Physiological reviews
Recent studies have indicated that arachidonic acid is primarily metabolized by cytochrome P-450 (CYP) enzymes in the brain, lung, kidney, and peripheral vasculature to 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) and that these compounds play critical roles in the regulation of renal, pulmonary, and cardiac function and vascular tone. EETs are endothelium-derived vasodilators that hyperpolarize vascular smooth muscle (VSM) cells by activating K(+) channels. 20… 

Role of 20-hydroxyeicosatetraenoic vascular system acid ( 20-HETE ) in

Recent findings implicating a critical role for 20-HETE in altering cardiovascular function in a variety of pathological conditions are summarized.

Regulation of renal microvascular 20-hydroxyeicosatetraenoic acid (20-HETE) levels.

The kidney possesses a large capacity to generate cytochrome P450 (CYP) dependent arachidonic acid (AA) metabolites, chiefly the ω and ω -1 hydroxylase-derived metabolites, and lesser amounts of epoxyeicosatrienoic acids (EETs), primarily 11,12 EETs.

Evidence that 20-HETE contributes to the development of acute and delayed cerebral vasospasm

Evidence that an elevation in the production of 20-HETE contributes to the initial fall in CBF following SAH and the later development of delayed vasospasm is examined.

Cytochrome P-450 monooxygenases in control of renal haemodynamics and arterial pressure in anaesthetized rats.

Total renal blood flow seems to be under vasodilator control of EETs whereas renal medullary perfusion under tonic suppression by 20-HETE, for the first in the whole kidney studies.

Molecular mechanisms and cell signaling of 20-hydroxyeicosatetraenoic acid in vascular pathophysiology.

The role of 20-HETE in vascular dysfunction, inflammation, ischemic and hemorrhagic stroke and cardiac and renal ischemia reperfusion injury in the brain, kidney and heart is focused on.

Cytochrome P-450-dependent metabolism of arachidonic acid in the kidney of rats with diabetes insipidus.

The results indicate that the expression of CYP4A protein and the renal formation of 20-HETE are elevated in the kidney of BB rats due to a lack of vasopressin and that chronic blockade of the formation of20-HetE and EETs with ABT promotes water excretion in vasoppressin-deficient BB rats by reducing the circulating levels of oxytocin, which is a weak vasopressedin agonist.

20-hydroxyeicosatetraenoic acid and angiotensin: a positive feedback system to cause hypertension.

  • J. Imig
  • Biology, Medicine
  • 2010
Significant evidence is provided that vascular 20-HETE levels increase in response to angiotensin II; however, the potential influence of 20- HETE on the renin-angiotens in system had not been previously investigated.

The Metabolites of Arachidonic Acid in Microvascular Function

Current research on pharmacological manipulation of certain components of the AA pathways (such as 20‐HETE production inhibition or prolongation of the life of epoxyeicoatrienoic acids(EETs) by inhibitors of soluble epoxide hydrolaze (sEH)promises effective therapy of cardiovascular and cerebrovascular diseases in the future.

Role of epoxyeicosatrienoic acids in renal functional response to inhibition of NO production in the rat.

It is concluded that NO tonically regulates epoxygenase activity and that EETs are renal vaosoconstrictors in vivo and contribute, at least in part, to the renal functional responses following inhibition of NO production.



Cytochrome P-450 arachidonate metabolites in rat kidney: characterization and hemodynamic responses.

The capacity of rat kidney to metabolize AA through cytochrome P-450-dependent oxygenases is established and the endogenous formation of the resulting eicosanoids is demonstrated, suggesting their potential relevance in the regulation of renal function.

Hypoxic pulmonary vasoconstriction is modified by P-450 metabolites.

  • D. ZhuE. Birks E. Jacobs
  • Biology, Medicine
    American journal of physiology. Heart and circulatory physiology
  • 2000
The data suggest that endogenously produced 20-HETE could modify rabbit pulmonary vascular tone, particularly under hypoxic conditions.

Inhibition of renal arachidonic acid ω-hydroxylase activity with ABT reduces blood pressure in the SHR.

  • P. SuK. KaushalD. Kroetz
  • Biology, Medicine
    American journal of physiology. Regulatory, integrative and comparative physiology
  • 1998
Results identify ABT as a selective inhibitor of renal CYP4A activity and provide further support for a role for 20-HETE in the regulation of blood pressure.

Inhibition of brain P-450 arachidonic acid epoxygenase decreases baseline cerebral blood flow.

Results implicate endogenous P-450 epoxides of AA in the regulation of basal blood flow in cerebral microcirculation and on nitric oxide synthase activity in homogenates of rat brain.

Formation and action of a P-450 4A metabolite of arachidonic acid in cat cerebral microvessels.

The potent vasoconstrictor effects of 20-HETE on cerebral vessels suggests that metabolites of P-450 enzymes of the 4A gene family could play an important role in regulating cerebral microvascular tone.

Dilation of cerebral arterioles by cytochrome P-450 metabolites of arachidonic acid.

The vasoactivity of EETs and AA on the cerebral microcirculation was determined, and data are consistent with brain cyclooxygenase metabolism of 5,6-EET with concomitant generation of dilator oxygen radicals.

The lung HETEs (and EETs) up.

  • E. JacobsD. Zeldin
  • Biology, Medicine
    American journal of physiology. Heart and circulatory physiology
  • 2001
A number of potential functions of P-450-derived arachidonate metabolites in the lungs are hypothesized, such as contribution to hypoxic pulmonary vasoconstriction, regulation of bronchomotor tone, control of the composition of airway lining fluid, and limitation of pulmonary inflammation.

Cytochrome P-450-dependent HETEs: profile of biological activity and stimulation by vasoactive peptides.

The quantity of HETEs released from the kidney, either under basal conditions or when stimulated by ANG II, and their biological profile suggest that subterminal HetEs may participate in renal mechanisms affecting vasomotion and tubular transport.

Role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip hypertension

Elevations in renal cortical or papillary blood flow, or both, may stimulate the release of a P-450-derived antihypertensive lipid from the kidney after unclipping of the renal artery in 1-K,1C hypertensive rats.