Characterization of endothelium-derived hyperpolarizing factor in the human forearm microcirculation

Halcox, Julian P. J., Narayanan, S., Cramer-Joyce, L., Mincemoyer, R. and Quyyumi, A. A. 2001. Characterization of endothelium-derived hyperpolarizing factor in the human forearm microcirculation. American Journal of Physiology Heart and Circulatory Physiology 280 (6) , H2470-h2477.

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Abstract

The identity of endothelium-dependent hyperpolarizing factor (EDHF) in the human circulation remains controversial. We investigated whether EDHF contributes to endothelium-dependent vasomotion in the forearm microvasculature by studying the effect of K+ and miconazole, an inhibitor of cytochrome P-450, on the response to bradykinin in healthy human subjects. Study drugs were infused intra-arterially, and forearm blood flow was measured using strain-gauge plethysmography. Infusion of KCl (0.33 mmol/min) into the brachial artery caused baseline vasodilation and inhibited the vasodilator response to bradykinin, but not to sodium nitroprusside. Thus the incremental vasodilation induced by bradykinin was reduced from 14.3 +/- 2 to 7.1 +/- 2 ml x min(-1) x 100 g(-1) (P < 0.001) after KCl infusion. A similar inhibition of the bradykinin (P = 0.014), but not the sodium nitroprusside (not significant), response was observed with KCl after the study was repeated during preconstriction with phenylephrine to restore resting blood flow to basal values after KCl. Miconazole (0.125 mg/min) did not inhibit endothelium-dependent or -independent responses to ACh and sodium nitroprusside, respectively. However, after inhibition of cyclooxygenase and nitric oxide synthase with aspirin and NG-monomethyl-L-arginine, the forearm blood flow response to bradykinin (P = 0.003), but not to sodium nitroprusside (not significant), was significantly suppressed by miconazole. Thus nitric oxide- and prostaglandin-independent, bradykinin-mediated forearm vasodilation is suppressed by high intravascular K+ concentrations, indicating a contribution of EDHF. In the human forearm microvasculature, EDHF appears to be a cytochrome P-450 derivative, possibly an epoxyeicosatrienoic acid.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Subjects:	R Medicine > R Medicine (General) R Medicine > RZ Other systems of medicine
Uncontrolled Keywords:	Administration Oral,Adult,Aspirin/administration & dosage,Biological Factors/metabolism*,Blood Flow Velocity/drug effects,Blood Flow Velocity/physiology,Brachial Artery/physiology,Bradykinin/administration & dosage,Cyclooxygenase Inhibitors/administration & dosage CytochromeP450nzymeInhibitors,CytochromeP450EnzymeSystem/metabolism,DoseResponseRelationshipDrug,EnzymeInhibitors/administration&dosage,Forearm/bloodsupply*,Forearm/physiology,Humans,InfusionsIntraArterial,Miconazole/administration&dosage,Microcirculation/drugeffects,Microcirculation/metabolism*,MiddleAged,Nitroprusside/administration&dosage,Phenylephrine/administration&dosage,Plethysmography,PotassiumChloride/administration&dosage,VasoconstrictorAgents/administration&dosage,VasodilatorAgents/administration&dosage,VasomotorSystem/drugeffects,VasomotorSystem/metabolism*,omegaNMethylarginine/administration & dosage Substances BiologicalFactors,CyclooxygenaseInhibitors,CytochromeP450EnzymeInhibitors,EnzymeInhibitors,VasoconstrictorAgents,VasodilatorAgents,endotheliumdependenthyperpolarizationfactor,Nitroprusside,Phenylephrine,omega-N-Methylarginine,Potassium Chloride,Miconazole,Cytochrome P-450 Enzyme System,Aspirin,Bradykinin
Additional Information:	Publication Types Clinical Trial Full Text Sources HighWire Other Literature Sources COS Scholar Universe Labome Researcher Resource - ExactAntigen/Labome Access more work from the authors - ResearchGate Molecular Biology Databases ACETYLSALICYLIC ACID - HSDB POTASSIUM CHLORIDE - HSDB PHENYLEPHRINE - HSDB
Publisher:	American Physiological Society
ISSN:	0363-6135
Related URLs:	http://ajpheart.physiology.org/
Last Modified:	19 Mar 2016 23:53
URI:	https://orca.cardiff.ac.uk/id/eprint/71136

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