20-HETE agonists and antagonists in the renal circulation

Alonso-Galicia, Magdalena; Falck, John R.; Reddy, K. Mohan; Roman, Richard J.

doi:10.1152/ajprenal.1999.277.5.f790

Cited by 101 publications

(121 citation statements)

References 20 publications

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“…Activated platelets in clotting blood are the likely source of thromboxane and 12-HETE in CSF after SAH. 20-HETE is one of the major metabolites of AA produced by the cerebral vasculature (1,15,16,25) and by polymorphonuclear leukocytes (PMNs) (5,33). Thus the levels of 20-HETE in CSF were measured after SAH in the present study.…”

Section: Discussionmentioning

confidence: 93%

20-HETE contributes to the acute fall in cerebral blood flow after subarachnoid hemorrhage in the rat

Kehl¹,

Cambj-Sapunar²,

Maier³

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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man. 20-HETE contributes to the acute fall in cerebral blood flow after subarachnoid hemorrhage in the rat. Am J Physiol Heart Circ Physiol 282: H1556-H1565, 2002. First published December 6, 2001 10.1152/ajpheart.00924.2001.-This study examined the effects of blocking the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) on the acute fall in cerebral blood flow after subarachnoid hemorrhage (SAH) in the rat. In vehicle-treated rats, regional cerebral blood flow (rCBF) measured with laser-Doppler flowmetry fell by 30% 10 min after the injection of 0.3 ml of arterial blood into the cisterna magna, and it remained at this level for 2 h. Pretreatment with inhibitors of the formation of 20-HETE, 17-octadecynoic acid (17-ODYA; 1.5 nmol intrathecally) and N-hydroxy-NЈ-(4-butyl-2-methylphenyl)formamidine (HET0016; 10 mg/kg iv), reduced the initial fall in rCBF by 40%, and rCBF fully recovered 1 h after induction of SAH. The concentration of 20-HETE in the cerebrospinal fluid rose from 12 Ϯ 2 to 199 Ϯ 17 ng/ml after SAH in vehicle-treated rats. 20-HETE levels averaged only 15 Ϯ 11 and 39 Ϯ 13 ng/ml in rats pretreated with 17-ODYA or HET0016, respectively. HET0016 selectively inhibited the formation of 20-HETE in rat renal microsomes with an IC50 of Ͻ15 nM and human recombinant CYP4A11, CYP4F2, and CYP4F3 enzymes with an IC50 of 42, 125, and 100 nM, respectively. These results indicate that 20-HETE contributes to the acute fall in rCBF after SAH in rats.

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Section: Discussionmentioning

confidence: 93%

20-HETE contributes to the acute fall in cerebral blood flow after subarachnoid hemorrhage in the rat

Kehl¹,

Cambj-Sapunar²,

Maier³

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…20-HETE increases vascular tone, in part, by inhibiting the activity of vascular smooth muscle K Ca channels, leading to membrane depolarization and a subsequent influx of calcium through L-type voltage-sensitive channels (1,18,52). When these channels were inhibited by TEA or IbTx before 20-HETE application, the arteriolar constriction to 20-HETE was dramatically reduced in rats fed normal salt but not in rats fed high salt (Fig.…”

Section: Discussionmentioning

confidence: 95%

“…Previous studies suggest that ANG II and norepinephrine (NE) may elicit vasoconstriction, in part, through 20-HETE production (1,20,24). Therefore, we also assessed arteriolar responsiveness to ANG II (1 ϫ 10 Ϫ9 M and 1 ϫ 10 Ϫ8 M, Sigma) and NE (1 ϫ 10 Ϫ7 M and 1 ϫ 10 Ϫ8 M, Sigma) before and after inhibition of 20-HETE formation with DDMS.…”

Section: Application Of Exogenous Vasoconstrictorsmentioning

confidence: 99%

High dietary salt reduces the contribution of 20-HETE to arteriolar oxygen responsiveness in skeletal muscle

Marvar

Falck²,

Boegehold

2007

American Journal of Physiology-Heart and Circulatory Physiology

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coupling of tissue blood flow to cellular metabolic demand involves oxygen-dependent adjustments in arteriolar tone, and arteriolar responses to oxygen can be mediated, in part, by changes in local production of 20-HETE. In this study, we examined the long-term effect of dietary salt on arteriolar oxygen responsiveness in the exteriorized, superfused rat spinotrapezius muscle and the role of 20-HETE in this responsiveness. Rats were fed either a normal-salt (NS, 0.45%) or high-salt (HS, 4%) diet for 4 -5 wk. There was no difference in steady-state tissue PO 2 between NS and HS rats, and elevation of superfusate oxygen content from 0% to 10% caused tissue PO 2 to increase by the same amount in both groups. However, the resulting reductions in arteriolar diameter and blood flow were less in HS rats than NS rats. Inhibition of 20-HETE formation with or 17-octadecynoic acid (17-ODYA) attenuated oxygen-induced constriction in NS rats but not HS rats. Exogenous 20-HETE elicited arteriolar constriction that was greatly reduced by the large-conductance Ca 2ϩ -activated potassium (K Ca) channel inhibitors tetraethylammonium chloride (TEA) and iberiotoxin (IbTx) in NS rats and a smaller constriction that was less sensitive to TEA or IbTx in HS rats. Arteriolar responses to exogenous angiotensin II were similar in both groups but more sensitive to inhibition with DDMS in NS rats. Norepinephrine-induced arteriolar constriction was similar and insensitive to DDMS in both groups. We conclude that 20-HETE contributes to oxygen-induced constriction of skeletal muscle arterioles via inhibition of K Ca channels and that a high-salt diet impairs arteriolar responses to increased oxygen availability due to a reduction in vascular smooth muscle responsiveness to 20-HETE. 20-hydroxyeicosatetraenoic acid; vascular control; blood flow; NaCl LOCAL OXYGEN AVAILABILITY is an important determinant of microvascular resistance and tissue blood flow (10,17,22,41), and consumption of a high-salt diet can lead to changes in resistance vessel function that alter the relationship between oxygen and vascular tone. For example, small gracilis muscle feed arteries from rats fed high salt for as little as 3 days consistently show an impaired dilator response to reduced oxygen levels (47, 48). However, the effect of oxygen on the tone of smaller arterioles in rat cremaster muscle is unchanged after 3 days on a high-salt diet (13). This suggests that either a longer period of high-salt intake is required to alter the oxygen responsiveness of these more distal resistance vessels or that there is a fundamental difference between extraparenchymal arteries and intramuscular arterioles in the susceptibility of oxygen-sensitive tone to dietary salt. The first aim of this study was to distinguish between these possibilities by determining whether a prolonged period of high-salt intake can change the relationship between oxygen and vascular tone in the arteriolar network of skeletal muscle.The mechanisms through which oxygen can influence resistance vessel to...

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“…NO can also induce vasodilation by inhibiting -hydroxylase, resulting in a decrease in the vasoconstricting metabolite 20-HETE (Alonso-Galicia et al, 1998;Sun et al, 2000). Both of these mechanisms contribute to vasodilation in the brain (Alonso-Galicia et al, 1999). However, NO could also favor vasoconstriction.…”

Section: Discussionmentioning

confidence: 99%

Glial Cells Dilate and Constrict Blood Vessels: A Mechanism of Neurovascular Coupling

Metea¹,

Newman²

2006

J. Neurosci.

546

584

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Neuronal activity evokes localized changes in blood flow. Although this response, termed neurovascular coupling, is widely used to monitor human brain function and diagnose pathology, the cellular mechanisms that mediate the response remain unclear. We investigated the contribution of glial cells to neurovascular coupling in the acutely isolated mammalian retina. We found that light stimulation and glial cell stimulation can both evoke dilation or constriction of arterioles. Light-evoked and glial-evoked vasodilations were blocked by inhibitors of cytochrome P450 epoxygenase, the synthetic enzyme for epoxyeicosatrienoic acids. Vasoconstrictions, in contrast, were blocked by an inhibitor of -hydroxylase, which synthesizes 20-hydroxyeicosatetraenoic acid. Nitric oxide influenced whether vasodilations or vasoconstrictions were produced in response to light and glial stimulation. Light-evoked vasoactivity was blocked when neuron-to-glia signaling was interrupted by a purinergic antagonist. These results indicate that glial cells contribute to neurovascular coupling and suggest that regulation of blood flow may involve both vasodilating and vasoconstricting components.

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20-HETE agonists and antagonists in the renal circulation

Cited by 101 publications

References 20 publications

20-HETE contributes to the acute fall in cerebral blood flow after subarachnoid hemorrhage in the rat

20-HETE contributes to the acute fall in cerebral blood flow after subarachnoid hemorrhage in the rat

High dietary salt reduces the contribution of 20-HETE to arteriolar oxygen responsiveness in skeletal muscle

Glial Cells Dilate and Constrict Blood Vessels: A Mechanism of Neurovascular Coupling

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