Mediation by prostaglandins of the nitric oxide‐induced neurogenic vasodilatation in rat skin

Holzer, Peter; Jocič, Milana; Peskar, Bernhard A.

doi:10.1111/j.1476-5381.1995.tb15081.x

Cited by 33 publications

(17 citation statements)

References 36 publications

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“…17 Interactions between K ϩ channels and prostaglandins have also been documented. 10,11,13,35,36 We, therefore, explored the relative contributions of interactions between K ϩ channels, prostaglandins, and cGMP in mediating NO-evoked dilatation of ocular vasculature. Using retinal and choroidal vessel preparations as well as isolated cultured endothelial cells, we found that NO-induced relaxation of these oculovascular beds is partly mediated by cGMP but more importantly is dependent on PGI 2 formation by the endothelium through a mechanism mostly independent of guanylate cyclase, which involves opening a K Ca channel.…”

Section: Discussionmentioning

confidence: 99%

A Major Role for Prostacyclin in Nitric Oxide–Induced Ocular Vasorelaxation in the Piglet

Hardy

Abran

Hou

et al. 1998

Circulation Research

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—We studied the mechanisms of retinal and choroidal vasorelaxation elicited by nitric oxide (NO) using piglet eyes. The NO donors sodium nitroprusside (SNP) and diethylamine-NONOate caused comparable concentration–dependent relaxation that was partially (≈40%) attenuated by the guanylate cyclase inhibitors methylene blue and LY83583 and reduced to a lesser extent (≈25%) by the inhibitor of cGMP–dependent kinase, KT 5823. In contrast, NO-induced dilatation (by NO donors and endogenous NO after stimulation with bradykinin) was substantially (≈70%) diminished by the K Ca channel blockers tetraethylammonium (TEA), charybdotoxin, and iberiotoxin; by the cyclooxygenase inhibitors indomethacin and ibuprofen; by the prostaglandin I (PGI 2 ) synthase inhibitor trans -2-phenyl cyclopropylamine (TPC); and by the removal of endothelium; whereas relaxation of endothelium-denuded vasculature to SNP was unaltered by indomethacin, TPC, and charybdotoxin but was nearly nullified by methylene blue and the K v channel blocker 4-aminopyridine. NO donors significantly increased PGI 2 synthesis and the putative PGI 2 receptor–coupled second messenger cAMP, from ocular vasculature (retinal microvessels and choroidal perfusate), and this increase in PGI 2 formation was markedly reduced by TPC, tetraethylammonium, charybdotoxin, and/or the removal of endothelium, but it was only slightly reduced by methylene blue and LY83583. Also, SNP and K Ca channel openers NS1619 and NS004 caused an increase in PGI 2 synthesis in cultured endothelial cells, which was virtually abolished by K Ca blockers. Finally, vasorelaxation to a cGMP analogue, 8-bromo cGMP, and protein kinase G stimulant β-phenyl-1, N 2 -etheno-8-bromoguanosine 3′:5′-cyclic monophosphate was mostly K v dependent and, in contrast to NO, largely unrelated to PGI 2 formation. In conclusion, data indicate that NO-induced ocular vasorelaxation is partly mediated by cGMP through its action on smooth muscle, and more importantly, by stimulating PGI 2 formation of endothelial origin via a mechanism mostly independent of guanylate cyclase, which involves the opening of a K Ca channel.

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Section: Discussionmentioning

confidence: 99%

A Major Role for Prostacyclin in Nitric Oxide–Induced Ocular Vasorelaxation in the Piglet

Hardy

Abran

Hou

et al. 1998

Circulation Research

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“…Although CGRP receptors are present on endothelial and vascular smooth muscle cells, it seems that in skin, CGRP-induced dilation is largely independent of NO synthesis. 89,90 However, the vasoconstrictor effect of ET-1 is known to be limited by its dilator action exerted via ET B receptors on endothelium. 91 Thus, it needs to be established whether the depressed erythematous response to ET-1 and the depressed dilator response to cold per se reported in primary Raynaud's patients, reflects an impaired dilator influence of NO rather than a deficit of CGRP-containing nerves.…”

Section: Calcitonin Gene-related Peptide (Cgrp)mentioning

confidence: 99%

Mechanisms of Raynaud’s disease

2005

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Raynaud's phenomenon is due to transient cessation of blood flow to the digits of the hands or feet. An attack of Raynaud’s phenomenon is classically manifested as triphasic color changes. The white phase is due to excessive vasoconstriction and cessation of regional blood flow. This phase is followed by a cyanotic phase, as the residual blood in the finger desaturates. The red phase is due to hyperemia as the attack subsides and blood flow is restored. An attack is frequently associated with pain and/or paresthesia due to sensory nerve ischemia. Variants of Raynaud’s phenomenon include acrocyanosis and primary livedo reticularis, each of which is associated with reduced skin blood flow, exacerbated by cold or emotional upset. Raynaud’s phenomenon in the absence of other disorders is primary Raynaud’s phenomenon, or Raynaud’s disease. The mechanisms of Raynaud’s disease include increased activation of the sympathetic nerves, in response to cold or emotion; an impaired habituation of the cardiovascular response to stress may contribute. In addition, there appears to be a local fault, which is likely multifactorial. This local fault is due to an alteration in vascular function rather than vascular structure. The alteration in vascular function may be related to increased sensitivity to cold of the adrenergic receptors on the digital artery vascular smooth muscle. In some cases, locally released or systemically circulating vasoconstrictors may participate, including endothelin, 5-hydroxytryptamine and thromboxane. A deficiency or increased degradation of nitric oxide, possibly due to increased oxidative stress, may be involved in some cases. These recent pathophysiological insights may lead to new therapeutic options.

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“…As mast cells are often juxtaposed to blood vessels and afferent nerve endings (Holzer, 1992) it could be hypothesized that interleukin-lß acts on these cells to stimulate the sequential formation of NO and prostaglandins which, in turn, contribute to the sensitization of afferent nerve endings. In addition, NO generated in the rat skin can by itself give rise to afferent nerve-mediated vasodilatation (Holzer and Jocic, 1994). Secondly, interleukin-1ß has been shown to stimulate the consecutive formation of NO and prostagtandin E 2 in vascular smooth muscle cells (lnoue et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…The activity of N°-nitro-o-arginine methyl ester to elevate blood pressure, which has been noted previously (Holzer et al, 1993), is not understood at present. N°-nitro-L-arginine methyl ester was given systemically since this route of administration did not significantly diminish cutaneous blood flow, whereas local application of the drug has been observed to , reduce skin blood flow to a significant extent (Holzer and Jocic, 1994). The use of s.c. N°-nitro-L-arginine methyl ester was regarded as impractible, therefore, given that local N°-nitro-L-arginine methyl ester could inhibit vasodilator responses solely by virtue of its vasoconstrictor effect.…”

Section: Discussionmentioning

confidence: 99%

“…This possibility was envisaged from the findings that the effects of interleukin-1ß on a variety of tissues and cells depend on the formation of NO as an intermediate messenger (Esplugues et al, 1993;Hogaboam et al, 1993;Inoue et al, 1993). Furthermore, it has been found that NO generated in the rat skin can give rise to afferent neiVe-mediated vasodilatation (Holzer and Jocic, 1994).…”

Section: Lntroductionmentioning

confidence: 99%

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Nitric oxide mediates the amplification by interleukin-1β of neurogenic vasodilatation in the rat skin

Herbert¹,

Holzer²

1994

European Journal of Pharmacology

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Blood flow in the plantar hindpaw skin of anaesthetized ratswas measured by Iaser Doppler flowmetry. Intraplantar injection of interleukin-lß (50 pg) significantly enhanced the hyperaemic response to intraplantar capsaicin (0.3 ,.,.g). Pretreatment with a neurotoxic dose of capsaicin reduced the capsaicin-evoked hyperaemia and prevented the facilitatory effect of interleukin-lß. Blockade of nitric oxide formation by N°-nitro-L-arginine methyl ester failed to affect the capsaicin-evoked vasodilatation but abolished its amplification by interleukin-lß. These data indicate that the enhancement by interleukin-lß of the capsaicin-induced hyperaemia involves thin afferent nerve fibres and depends on nitric mdde as esse'ntial intermediate. lntroductionThe cutaneous vasodilatation induced by topical administration of capsaicin is to a large extent mediated by activation of thin afferent neiVe fibres and release of vasoactive peptides from their peripheral endings (Holzer, 1992). We have previously shown that the inflammatory cytokine interleukin-lß enhances the hyperaemia evoked by injection of capsaicin into the rat plantar hindpaw skin in a prostaglandin-dependent manner (Herbert and Holzer, 1994). Since the vasodilator effect of calcitonin gene-related peptide (CGRP), the major neuragenie mediator of the capsaicin-induced vasodilatation (Hughes and Brain, 1991;Brain et al., 1993), was not altered by interleukin-1ß it was concluded that the effect of the cytokine was brought about by sensitization of afferent neiVe endings to capsaicin (Herbert and Holzer, 1994).This inference was further tested here by examining the effect of interleukin-1/3 in rats in which thin afferent neurones bad been defunctionalized by systemic

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Mediation by prostaglandins of the nitric oxide‐induced neurogenic vasodilatation in rat skin

Cited by 33 publications

References 36 publications

A Major Role for Prostacyclin in Nitric Oxide–Induced Ocular Vasorelaxation in the Piglet

A Major Role for Prostacyclin in Nitric Oxide–Induced Ocular Vasorelaxation in the Piglet

Mechanisms of Raynaud’s disease

Nitric oxide mediates the amplification by interleukin-1β of neurogenic vasodilatation in the rat skin

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