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R Popp

Publications and source records attributed to R Popp.

At least 19 recordsLinked to original sources
PubMed2004

Outcomes of CPAP treatment in a sleep laboratory specialized in neuropsychiatry.

The rapidly increasing number of sleep laboratories implicates their specialization into various fields of sleep medicine. In our sleep laboratory that specializes in neuropsychiatry, patients with the symptoms typical for the obstructive sleep apnea/hypopnea syndrome (OSAHS) were routinely redirected to a local respiratory clinic. Some patients, however, admitted to our center for other reasons revealed OSAHS in nocturnal polysomnography. The purpose of this retrospective study was to assess the outcome of CPAP in treating the sleepiness in this group of patients. Our material consisted of 36 patients who started CPAP therapy due to OSAHS diagnosed in our laboratory in the year 2000 and who came for a routine checkup in 2001. The sleepiness was assessed by using the Epworth Sleepiness Scale (ESS). After CPAP, the mean group ESS score decreased from 10.9 +/-4.4 to 8.5 +/-4.3 points (P<0.01). Some patients showed, however, persisting excessive sleepiness (PTS) after CPAP, defined as ESS >or=12. We overviewed the documentation of those patients in search for the possible causes of PTS. We identified the following causes: narcolepsy - 1 patient, insufficient CPAP pressure - 1 patient, low CPAP compliance, fewer than 2 h/night, - 2 patients. In 5 other patients we found CPAP compliance to be between 2.0 and 4.5 h/night, which is less likely to be the cause of PTS. In 1 patient no cause was identified. Our patients showed relatively mild sleepiness before CPAP and only a slight improvement under CPAP. The CPAP noncompliance seems the most prevailing reason for CPAP failure, but in some patients the cause of PTS could not be unraveled by using standard diagnostic tools and some additional measures are to be employed to resolve the issue.

Continuous Positive Airway Pressure↗
PubMed2003

Hyperthyroidism enhances endothelium-dependent relaxation in the rat renal artery.

OBJECTIVE: Hyperthyroidism has pronounced effects on vascular function and endothelium-dependent relaxation. The aim of the present study was to identify mechanisms underlying hyperthyroidism-induced alterations in endothelial function in rats. METHODS: Animals were subjected to either a single injection (36 h) or 8 weeks treatment with the thyroid hormone triiodothyronine (T3, i.p.). Vascular reactivity and agonist-induced hyperpolarization were studied in isolated renal arteries. Endothelial nitric oxide (NO) synthase expression and cyclic AMP accumulation were determined in aortic segments. RESULTS: Endothelium-dependent relaxations to acetylcholine (ACh) were enhanced by T3 36 h after injection and after treatment for 8 weeks. Thirty-six hours after T3 application, relaxation mediated by the endothelium-derived hyperpolarizing factor (EDHF) and by endothelium-derived NO were significantly enhanced. After 8 weeks treatment with T3, however, EDHF-mediated relaxation was impaired, whereas NO-mediated relaxation remained enhanced. KCl- and ACh-induced hyperpolarizations were more pronounced in arteries from rats treated with T3 for 36 h compared to control, whereas in arteries from rats treated with T3 for 8 weeks both responses were attenuated. In rats treated for 36 h, vascular cyclic AMP levels were enhanced in the aorta and inhibition of protein kinase A attenuated EDHF-mediated relaxations of the renal artery without affecting responses in arteries from the control group. In the aorta from rats treated with T3 for 8 weeks, the expression of the endothelial NO synthase was markedly up-regulated (463+/-68%). CONCLUSIONS: These data indicate that short-term treatment with T3 increases endothelium-dependent relaxation, most probably by increasing vascular cyclic AMP content. Following treatment with T3 for 8 weeks, expression of the endothelial NO synthase was enhanced. During this phase, NO appears to be the predominant endothelium-derived vasodilator.

Acetylcholine↗
PubMed2002

The extracellular regulated kinases (ERK) 1/2 mediate cannabinoid-induced inhibition of gap junctional communication in endothelial cells.

1. Cannabinoids are potent inhibitors of endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxations. We set out to study the mechanism underlying this effect and the possible role of cannabinoid-induced changes in intercellular gap junction communication. 2. In cultured endothelial cells, Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and the cannabinoid receptor agonist HU210, increased the phosphorylation of extracellular regulated kinases 1/2 (ERK1/2) and inhibited gap junctional communication, as determined by Lucifer Yellow dye transfer and electrical capacity measurements. 3. Delta(9)-THC elicited a pronounced increase in the phosphorylation of connexin 43, which was sensitive to PD98059 and U0126, two inhibitors of ERK1/2 activation. Inhibition of ERK1/2 also prevented the Delta(9)-THC-induced inhibition of gap junctional communication. 4. Delta(9)-THC prevented both the bradykinin-induced hyperpolarization and the nitric oxide and prostacyclin-independent relaxation of pre-contracted rings of porcine coronary artery. These effects were prevented by PD98059 as well as U0126. 5. In the absence of Delta(9)-THC, neither PD98059 nor U0126 affected the NO-mediated relaxation of coronary artery rings but both substances induced a leftward shift in the concentration - relaxation curve to bradykinin when diclofenac and N(omega)nitro-L-arginine were present. Moreover, PD98059 and U0126 prolonged the bradykinin-induced hyperpolarization of porcine coronary arteries, without affecting the magnitude of the response. 6. These results indicate that the cannabinoid-induced activation of ERK1/2, which leads to the phosphorylation of connexin 43 and inhibition of gap junctional communication, may partially account for the Delta(9)-THC-induced inhibition of EDHF-mediated relaxation. Moreover, the activation of ERK1/2 by endothelial cell agonists such as bradykinin, appears to exert a negative feedback inhibition on EDHF-mediated responses.

Animals↗
PubMed2001

Cyclic stretch enhances the expression and activity of coronary endothelium-derived hyperpolarizing factor synthase.

Endothelium-derived hyperpolarizing factor (EDHF) mediates NO/prostacyclin-independent relaxation in the coronary circulation. Because hemodynamic stimuli modulate endothelial gene expression and because coronary arteries are subjected to pronounced variations in vessel distension, we determined the effects of cyclic stretch on the expression and activity of the coronary EDHF synthase/cytochrome P450 (CYP) 2C8/9. In cultured porcine coronary and human umbilical vein endothelial cells, acute application of cyclic stretch (6%, 1 Hz, 10 minutes) elicited the generation of 8,9-epoxyeicosatrienoic acid (EET), 11,12-EET, and 14,15-EET. Prolonged stretch (4 to 36 hours) increased the expression of CYP 2C mRNA and protein 5- to 10-fold and was accompanied by a 4- to 8-fold increase in EET generation. A corresponding increase in CYP 2C mRNA and protein was also observed in pressurized segments of porcine coronary artery perfused under pulsatile conditions (8%, 1 Hz) for 6 hours. Although in cultured endothelial cells, cyclic stretch elicited the rapid activation of tyrosine kinases as well as Akt and the p38 mitogen-activated protein kinase, the mechanism by which cyclic stretch induces the expression of CYP 2C could not be elucidated, because inhibitors of these pathways induced CYP 2C expression in cells maintained under static conditions. These results have identified coronary EDHF synthase/CYP 2C as a novel mechanosensitive gene product in native and cultured endothelial cells. Because this enzyme generates both EETs and superoxide anions, this finding has wide-reaching implications for vascular homeostasis in conditions of manifest endothelial dysfunction.

8,11,14-Eicosatrienoic Acid↗
PubMed2001

The coronary endothelium-derived hyperpolarizing factor (EDHF) stimulates multiple signalling pathways and proliferation in vascular cells.

In the present study we determined whether the endothelium-derived hyperpolarizing factor (EDHF), in addition to its acute effects on vascular tone, activates intracellular signalling pathways other than those associated with Ca2+-dependent K+ channels. EDHF was generated by rhythmic distension of porcine coronary arteries under conditions of combined nitric oxide (NO) synthase/cyclo-oxygenase blockade, and the EDHF-containing luminal incubate was applied to cultured human coronary endothelial or smooth muscle cells. In both cell types, the luminal incubate activated tyrosine kinases, the mitogen-activated protein (MAP) kinases, extracellular signal regulated kinases 1 and 2 (Erk1/2) and p38, as well as protein kinase B/Akt. The constituent responsible for Erk1/2 phosphorylation was identified as a cytochrome P450 (CYP) metabolite, as Erk1/2 activation was attenuated by pretreating the EDHF donor with the CYP 2C inhibitor sulfaphenazole as well as by CYP 2C antisense oligonucleotides. Erk1/2 phosphorylation in detector cells was also observed following the transfer of supernatant from cultured endothelial cells treated with the CYP inducer beta-naphthoflavone. The CYP 2C product 11,12-epoxyeicosatrienoic acid (11,12-EET) also activated tyrosine kinases, Erk1/2 and p38 MAP kinase. Overexpression of CYP 2C8 in native porcine coronary artery endothelial cells resulted in an increase in endothelial 11,12-EET production and Erk1/2 phosphorylation compared to that detected in untreated cells or cells transfected with an antisense CYP 2C8. Endothelial cell number was unaffected by transfection with LacZ or CYP 2C8 antisense but was significantly enhanced in cells overexpressing CYP 2C8. These observations indicate that EDHF/11,12-EET is not simply a vasodilator and that its continuous release under pulsatile conditions in vivo may affect vascular cell signalling and proliferation.

8,11,14-Eicosatrienoic Acid↗
PubMed2000

Nifedipine increases cytochrome P4502C expression and endothelium-derived hyperpolarizing factor-mediated responses in coronary arteries.

In addition to NO and prostacyclin, endothelial cells release a factor that elicits vasodilatation by hyperpolarizing the underlying vascular smooth muscle cells. In some vascular beds, this so-called endothelium-derived hyperpolarizing factor (EDHF) displays the characteristics of a cytochrome P450 (CYP)-derived arachidonic acid metabolite, such as an epoxyeicosatrienoic acid. Native porcine and cultured human coronary artery endothelial cells were screened for CYP epoxygenases, and CYP2B, CYP2C, and CYP2J were detected with reverse transcription-polymerase chain reaction. The CYP inducer beta-naphthoflavone and the Ca(2+) antagonist nifedipine significantly increased CYP2C mRNA but did not change the expression of CYP2J or CYP2B. To determine the relationship between CYP2C expression and EDHF production in native endothelial cells, we incubated porcine coronary arteries with nifedipine. Nifedipine enhanced endothelial CYP2C protein expression, as well as the generation of 11,12-epoxyeicosatrienoic acid. In organ bath experiments, pretreatment with nifedipine enhanced bradykinin-induced, EDHF-mediated relaxations as well as the concomitant hyperpolarization of smooth muscle cells. The specific CYP2C9 inhibitor sulfaphenazole, on the other hand, significantly attenuated EDHF-mediated hyperpolarization and relaxation. These results demonstrate that in porcine coronary arteries, the elevated expression of a CYP epoxygenase, homologous to CYP2C8/9, is associated with enhanced EDHF-mediated hyperpolarization in response to bradykinin. Therefore, we propose that an isozyme of CYP2C is the most likely candidate for the CYP-dependent EDHF synthase in porcine coronary arteries.

8,11,14-Eicosatrienoic Acid↗
PubMed2000

The value of book distribution in a clinic-based literacy intervention program.

The purpose of this study was to determine whether anticipatory guidance at well-child visits (WCV) that included early literacy development and the provision of books by the examining physician changed family literacy practices. It was conducted in an inner-city pediatric clinic that serves as the continuity practice site for pediatric and pediatric/internal medicine residents. There were 352 children (181 treatment: 171 control), aged 2 to 24 months, enrolled in this prospective, controlled study. The health care providers underwent training on literacy and on how to incorporate this information during WCV. Anticipatory guidance on safety, development, and early literacy was given to all parents. Additionally, the treatment group received an age-appropriate book at each WCV. There were 1,263 visits made (686 treatment, 577 control). Questionnaires were completed by parents on physician helpfulness and by physicians on parental receptiveness. Parental ratings on physician helpfulness were higher in the treatment group than in the control group (p<0.05). Physician's rating of parental receptiveness was also higher in the treatment group than in the control group (p<0.05). Two years after enrollment, mother-child pairs who received guidance and a book were two times more likely to report enjoyment in reading together than the controls who received guidance but no book. We conclude that anticipatory guidance that included early literacy development and distribution of books at WCV resulted in increased family literacy orientation, parental receptiveness, and perception of physician helpfulness.

Child Guidance↗
PubMed1999

Cytochrome P450 2C is an EDHF synthase in coronary arteries.

In most arterial beds a significant endothelium-dependent dilation to various stimuli persists even after inhibition of nitric oxide synthase and cyclo-oxygenase. This dilator response is preceded by an endothelium-dependent hyperpolarization of vascular smooth muscle cells, which is sensitive to a combination of the calcium-dependent potassium-channel inhibitors charybdotoxin and apamin, and is assumed to be mediated by an unidentified endothelium-derived hyperpolarizing factor (EDHF). Here we show that the induction of cytochrome P450 (CYP) 2C8/34 in native porcine coronary artery endothelial cells by beta-naphthoflavone enhances the formation of 11,12-epoxyeicosatrienoic acid, as well as EDHF-mediated hyperpolarization and relaxation. Transfection of coronary arteries with CYP 2C8/34 antisense oligonucleotides results in decreased levels of CYP 2C and attenuates EDHF-mediated vascular responses. Thus, a CYP-epoxygenase product is an essential component of EDHF-mediated relaxation in the porcine coronary artery, and CYP 2C8/34 fulfils the criteria for the coronary EDHF synthase.

8,11,14-Eicosatrienoic Acid↗
PubMed1999

Proinflammatory mediators chronically downregulate the formation of the endothelium-derived hyperpolarizing factor in arteries via a nitric oxide/cyclic GMP-dependent mechanism.

BACKGROUND: Endothelium-dependent dilator responses mediated by NO and endothelium-derived hyperpolarizing factor (EDHF) are altered in arteriosclerosis and sepsis. The possibility that proinflammatory mediators that stimulate the expression of inducible NO synthase (NOS II) affect the generation of EDHF was examined in isolated arteries. METHODS AND RESULTS: Under combined blockade of NOS and cyclooxygenase, EDHF-mediated relaxation elicited by several agonists was significantly attenuated in rabbit carotid and porcine coronary arteries exposed to cytokines and lipopolysaccharide. The blunted relaxation was coincident with NOS II expression and was prevented by inhibition of NOS II as well as of global protein synthesis. The NO donor CAS 1609 and 8-bromo-cGMP mimicked the proinflammatory mediator effect. In contrast, long-term blockade of endothelial NO generation increased the relaxation in carotid but not in coronary arteries. Proinflammatory mediators reduced the synthesis of EDHF assessed as hyperpolarization of vascular smooth muscle cells elicited by the effluent from bradykinin-stimulated coronary arteries. Proinflammatory mediators induced NOS II expression in cultured endothelial cells and decreased the expression of cytochrome P450 enzymes, which are the most probable candidates for the synthesis of EDHF. CONCLUSIONS: Proinflammatory mediators inhibit the formation of EDHF in isolated arteries. This impairment is coincident with NOS II expression in the arterial wall and seems to be mediated through the induced generation of NO, which downregulates the putative EDHF-forming enzyme. Thus, a decreased formation of EDHF may contribute to the endothelial dysfunction in arteriosclerosis and sepsis.

Animals↗
PubMed1999

Inhibition of the production of endothelium-derived hyperpolarizing factor by cannabinoid receptor agonists.

1. The endogenous cannabinoid, anandamide, has been reported to induce an 'endothelium-derived hyperpolarizing factor (EDHF)-like' relaxation in vitro. We therefore investigated the effects of cannabinoid CB1 receptor agonists; HU 210, delta9-tetrahydrocannabinol (delta9-THC) and anandamide, and a CB1 antagonist/inverse agonist, SR 141716A, on nitric oxide (NO) and EDHF-mediated relaxation in precontracted rings of porcine coronary, rabbit carotid and mesenteric arteries. 2. In rings of mesenteric artery HU 210 and delta9-THC induced endothelium- and cyclo-oxygenase-independent relaxations which were sensitive to SR 141716A. Anandamide (0.03-30 microM) induced a slowly developing, endothelium-independent relaxation which was abolished by diclofenac and was therefore mediated by cyclo-oxygenase product(s). None of the CB1 agonists tested affected the tone of precontracted rings of rabbit carotid or porcine coronary artery. 3. In endothelium-intact segments, HU 210, delta9-THC and anandamide did not affect NO-mediated responses but under conditions of continuous NO synthase/cyclo-oxygenase blockade, significantly inhibited acetylcholine and bradykinin-induced relaxations which are attributed to the production of EDHF. The effects of HU 210 and delta9-THC were not observed when experiments were performed in the presence of SR 141716A suggesting the involvement of the CB1 receptor. 4. In a patch clamp bioassay of EDHF production, HU 210 decreased the EDHF-mediated hyperpolarization of detector smooth muscle cells when applied to the donor segment but was without effect on the membrane potential of detector cells. The inhibition of EDHF production was unrelated to alterations in Ca2+ -signalling or cytochrome P450 activity. 5. These results suggest that the activation of endothelial CB1 receptors appears to be negatively coupled to the production of EDHF.

Animals↗
PubMed1999

Spiral bundle nailing for subcapital humeral fractures: preliminary report of the method of Henning.

This is a preliminary report of 31 patients treated with Henning's spiral bundle nails for subcapital humeral fractures. Complications included motion restriction at the elbow joint (n = 4), elbow pain caused by pin migration (n = 2), misalignment attributable to incorrect reduction (n = 4), and redislocation attributable to improper technique (n = 1), humeral head perforation (n = 3), caudal subluxation of the humeral head (n = 3), and local infections at the insertion site (n = 1). Immobilization was 3 weeks on average. By using the scoring scheme of Constant and Murley, 11 patients showed a moderate result, whereas 19 patients had an excellent outcome.

Adult↗
PubMed1998

Pulsatile stretch in coronary arteries elicits release of endothelium-derived hyperpolarizing factor: a modulator of arterial compliance.

To date, the release of the endothelium-derived hyperpolarizing factor (EDHF) has been demonstrated only in response to receptor-dependent Ca2+-elevating agonists. Since endothelial cells in situ are continuously subjected to rhythmic distension, we investigated the effect of rhythmic stretch on the release of EDHF from isolated porcine coronary arteries. In the combined presence of diclofenac and N(G)-nitro-L-arginine (L-NNA), sinusoidal pressure oscillations (from 40 to 50 mm Hg, 4 minutes, 1.5 Hz) led to simultaneous oscillations in the external diameter of coronary artery segments, the amplitude of which were decreased by iberiotoxin and apamin and also by endothelial denudation. In order to directly demonstrate the release of EDHF, the intraluminal solution from endothelium-intact coronary segments exposed to pulsatile stretch was applied to detector rat aortic smooth muscle cells, the membrane potential of which was continuously measured using the patch-clamp technique. The hyperpolarization of detector cells induced by the intraluminal solution was proportional to the amplitude of the pressure oscillations applied to the donor artery and was attenuated by either preincubation of donor arteries with 17-octadecynoic acid or application of either tetrabutylammonium or iberiotoxin to detector cells. In contrast to the bradykinin-induced release of EDHF, the EDHF synthesized in response to pulsatile stretch did not exhibit any tachyphylaxis. These findings demonstrate for the first time that the synthesis of EDHF in coronary arteries can be mechanically stimulated by rhythmic vessel wall distension and suggest that the continuous release of EDHF may contribute to the adjustment of an adequate vascular compliance and to the control of coronary blood flow.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

Recommendations for training in performance and interpretation of stress echocardiography. Committee on Physician Training and Education of the American Society of Echocardiography.

Stress echocardiography has emerged as a clinically useful procedure in the management of patients with ischemic heart disease and other conditions. However, the accuracy of this test relies on the ability of those who carry out the technical aspects of the test and depends critically on proper interpretation of the images. Appreciation of wall motion abnormalities is generally acknowledged as one of the most difficult skills to master in echocardiography. There is consensus that this is also one of the most difficult skills to teach. Appreciating stress-induced changes in wall motion, which sometimes are subtle, requires a significant commitment to initial training in this skill and its maintenance. This document provides recommendations for physician training in stress echocardiography.

Cardiology↗
PubMed1997

Nitric oxide and endothelium-derived hyperpolarizing factor: formation and interactions.

Nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) represent the two major endothelial autacoids involved in the local control of vascular tone. Here we describe a novel pathway leading to the calcium-independent activation of the endothelial NO synthase by shear stress and enhanced cellular tyrosine phosphorylation. In addition we present evidence that NO inhibits the formation of EDHF, which we have characterized as a transferable, beta-naphthoflavone-inducible P450-dependent metabolite of arachidonic acid.

Animals↗
PubMed1997

Endothelium-derived hyperpolarizing factor, but not nitric oxide, is reversibly inhibited by brefeldin A.

The subcellular localization of the enzymes synthesizing endothelium-derived vasodilator autacoids has been proposed to play a role in determining the ability of endothelial cells to enhance autacoid production in response to stimulation. We therefore investigated the effects of brefeldin A-induced disruption of the Golgi apparatus and Golgi-plasma membrane trafficking on the production of nitric oxide (NO), prostacyclin, and the endothelium-derived hyperpolarizing factor (EDHF) by native and cultured endothelial cells. In porcine coronary artery segments, brefeldin A (35 micromol/L, 90 minutes) did not affect relaxations to sodium nitroprusside or the K+ channel opener cromakalim but elicited a rightward shift in the concentration-response curve to bradykinin without altering the maximum vasodilator response (Rmax). Brefeldin A failed to attenuate the bradykinin-induced, NO-mediated relaxation under depolarizing conditions but inhibited the bradykinin response under conditions of combined cyclooxygenase/NO synthase blockade, suggesting that this agent selectively interferes with the production of EDHF. Indeed, incubation of porcine coronary arteries with brefeldin A, which did not affect the bradykinin-induced accumulation of either cyclic GMP or 6-keto-prostaglandin F1alpha, markedly and reversibly attenuated the EDHF-mediated hyperpolarization of detector smooth muscle cells in a patch-clamp bioassay system. The microtubule destabilizer nocodazole also affected both the EC50 and Rmax to bradykinin in porcine coronary arteries. Since EDHF is thought to be a cytochrome P450-derived metabolite of arachidonic acid and both brefeldin A and nocodazole are known to interfere with the targeting of cytochrome P450 from the Golgi apparatus to the plasma membrane, it is conceivable that brefeldin A inhibits EDHF formation by preventing the targeting of the EDHF-synthesizing enzymes to the plasma membrane.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

A transferable, beta-naphthoflavone-inducible, hyperpolarizing factor is synthesized by native and cultured porcine coronary endothelial cells.

1. The vascular endothelium releases a hyperpolarizing factor (endothelium-derived hyperpolarizing factor, EDHF) tentatively identified as a cytochrome P450-derived arachidonic acid metabolite. However, there is still controversy concerning its transferability and identity. We designed a bioassay system for assessing EDHF release in which the membrane potential was recorded in cultured vascular smooth muscle cells located downstream from donor endothelial cells. 2. Under combined nitric oxide (NO) synthase and cyclo-oxygenase blockade with NG-nitro-L-arginine (100 mumol l-1) and diclofenac (10 mumol l-1), the superfusate from bradykinin (30 mumol l-1)-stimulated, cultured porcine coronary endothelial cells induced a distinct hyperpolarization followed by a depolarization. Direct application of bradykinin to the smooth muscle cells resulted solely in membrane depolarization. Similar results were obtained using bradykinin-stimulated porcine coronary arteries as donor. 3. Single-channel current measurements suggest that this EDHF-induced hyperpolarization was elicited by the activation of Ca(2+)-dependent K+ channels. 4. Increasing the transmural pressure within the donor segment significantly enhanced the duration, but not the amplitude of the hyperpolarization induced by the effluate from bradykinin-stimulated donor segments. 5. Inhibition of P450 oxygenase activity with clotrimazole (3 mumol l-1) or 17-octadecynoic acid (3 mumol l-1) abolished EDHF release from the coronary endothelium, while the P450-derived arachidonic acid metabolite, 5,6-epoxyeicosatrienoic acid, induced a hyperpolarization of detector smooth muscle cells almost identical to that induced by EDHF. Moreover, induction of P450 activity by beta-naphthoflavone (3 mumol l-1, 48 h), significantly increased the bradykinin-induced release of EDHF. 6. These findings suggest that the vascular endothelium releases a transferable hyperpolarizing factor, chemically distinct from NO and prostacyclin, in response to agonists and mechanical stimulation. This beta-naphthoflavone-inducible EDHF appears to be a cytochrome P450-derived metabolite of arachidonic acid, which elicits hyperpolarization by activation of Ca(2+)-dependent K+ channels.

8,11,14-Eicosatrienoic Acid↗
PubMed1996

Nitric oxide attenuates the release of endothelium-derived hyperpolarizing factor.

BACKGROUND: The contribution of the endothelium-derived hyperpolarizing factor (EDHF), proposed to be a cytochrome P450-derived metabolite of arachidonic acid, to endothelium-dependent dilatation under physiological conditions has yet to be established, because its effect can be detected only after inhibition of NO synthase and cyclooxygenase. The possibility that NO exerts a feedback inhibition on EDHF formation was studied in isolated perfused arterial segments. METHODS AND RESULTS: Under combined blockade of NO synthase and cyclooxygenase, the EDHF-mediated vasodilatation elicited by receptor-dependent agonists in rabbit carotid and porcine coronary arteries was significantly attenuated by the NO donors C87-3786 and CAS 1609. The endothelium-independent dilatation elicited by isoproterenol was not altered by either NO donor. In NG-nitro-L-arginine-treated carotid artery segments, C87-3786 significantly attenuated the acetylcholine-induced increase in 6-keto-prostaglandin F1 alpha release, which was taken as an index of arachidonic acid liberation. In parallel experiments using cultured human endothelial cells, C87-3786 attenuated the Ca2+ response to bradykinin. The release of EDHF from a luminally perfused porcine coronary artery was detected by recording the membrane potential of downstream-situated cultured rat aortic smooth muscle cells. The NO donor C87-3786 had no effect on the hyperpolarization elicited by preformed EDHF but markedly inhibited its release from bradykinin-stimulated donor segments. CONCLUSIONS: These findings indicate that under physiological conditions, the production of EDHF is damped by NO. Therefore, it follows that when NO synthesis is impaired, alleviation of this intrinsic inhibition may, at least in part, maintain endothelial vasodilator function.

6-Ketoprostaglandin F1 alpha↗