The vasodilating effect of glucose differs among vessels at different branching level in the porcine retina ex vivo

Jensen, Peter Kryger; Aalkjær, Christian; Bek, Toke

doi:10.1016/j.exer.2018.11.006

Cited by 10 publications

(4 citation statements)

References 42 publications

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“…[3][4][5][6] In the macular area, vessel diameters and flow have been studied in perifoveal capillaries, 7,8 whereas less evidence has been obtained about the extrafoveal microcirculation. 9,10 Smaller retinal vessels outside the macular area are difficult to study, but the relevance of also investigating blood flow in this zone is testified by observations of differences in diameter regulation, 11 oxygen saturation, 12 and ischemic conditioning 13 in vessels supplying the macular area and the retinal periphery.…”

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confidence: 99%

Reduced Oxygen Extraction in the Retinal Periphery When the Arterial Blood Pressure Is Increased by Isometric Exercise in Normal Persons

Bek

Jeppesen

2021

Invest. Ophthalmol. Vis. Sci.

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confidence: 99%

Reduced Oxygen Extraction in the Retinal Periphery When the Arterial Blood Pressure Is Increased by Isometric Exercise in Normal Persons

Bek

Jeppesen

2021

Invest. Ophthalmol. Vis. Sci.

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“… 10 Recently, attention has been directed at different effects of intra- and extravascular application of vasoactive compounds 11 and the role of pre-capillary arterioles and capillaries for regulating retinal blood flow. 12 – 14 However, the effects of different routes of application of ATP and the role of the compound for the diameter regulation of smaller retinal vessels have not been studied in detail.…”

mentioning

confidence: 99%

Differential Effects of Intra- and Extravascular ATP on the Diameter of Porcine Vessels at Different Branching Levels Ex Vivo

Ernst

Jensen

Aalkjær

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Adenosine triphosphate (ATP) is involved in the diameter regulation of retinal vessels. The compound has been shown to induce both constriction and dilatation, but the detailed mechanisms underlying these effects and the site of action of the compound are not known in detail. Therefore, the purpose of the present study was to investigate whether the vasoactive effects of ATP on retinal vessels depend on intra-and extravascular application, and to study whether the effects differ at different vascular branching levels. METHODS. Diameter changes in arterioles, pre-capillary arterioles, and capillaries were studied in perfused porcine hemiretinas (n = 48) ex vivo after intra-and extravascular application of the nondegradable ATP analogue ATP-γ-S or ATP in the presence or not of antagonists to the CD73/ecto-5-nucleotidase (AOPCP), the P2-purinergic receptor (PPADS), the A3-adenosine receptor (MRS1523), and the synthesis of cyclooxygenase products (ibuprofen). RESULTS. Intravascular ATP-induced constriction and extravascular ATP-induced dilatation of retinal arterioles, pre-capillary arterioles and capillaries, and dilatation was inhibited by ibuprofen. Both constriction and dilatation of arterioles were inhibited by antagonizing ATP degradation. Furthermore, constriction at all three branching levels was antagonized by blocking the A3 purinoceptor, whereas constriction in arterioles and pre-capillary arterioles was antagonized by blocking the P2 purinoceptor. CONCLUSIONS. ATP affects the diameter of retinal arterioles, pre-capillary arterioles, and capillaries through different pathways, and the effects depend on whether the compound is administered intravascularly or extravascularly. This may form the basis for selective interventions on retinal vascular disease with differential involvement of vessels at different branching levels.

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“…Many vasodilators have different dilation effects on large and small vessels, which can affect some specific diseases. For example, the dilation of large vessels, such as the coronary artery, can alleviate myocardial ischemia ( Simsek et al, 2021 ), while the dilation of small vessels increases peripheral resistance ( Jensen et al, 2019 ). At present, our research is carried out on only the rabbit thoracic aorta, which is a large vessel.…”

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Vasodilatory Effect of Guanxinning Tablet on Rabbit Thoracic Aorta is Modulated by Both Endothelium-Dependent and -Independent Mechanism

Ling

Shi²,

et al. 2021

Front. Pharmacol.

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Vasodilatory therapy plays an important role in the treatment of cardiovascular diseases, especially hypertension and coronary heart disease. Previous research found that Guanxinning tablet (GXNT), a traditional Chinese compound preparation composed of Salvia miltiorrhiza (Danshen) and Ligusticum chuanxiong (Chuanxiong), increase blood flow in the arteries, but whether vasodilation plays a role in this effect remains unclear. Here, we found that GXNT significantly alleviated the vasoconstriction of isolated rabbit thoracic aorta induced by phenylephrine (PE), norepinephrine (NE), and KCl in a dose-dependent manner with or without endothelial cells (ECs). Changes in calcium ion levels in vascular smooth muscle cells (VSMCs) showed that both intracellular calcium release and extracellular calcium influx through receptor-dependent calcium channel (ROC) declined with GXNT treatment. Experiments to examine potassium channels suggested that endothelium-denuded vessels were also regulated by calcium-activated potassium channels (Kca) and ATP-related potassium channels (KATP) but not voltage-gated potassium channels (kv) and inward rectifying potassium channels (KIR). For endothelium-intact vessels, the nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) contents in vascular tissue obviously increased after GXNT treatment, and pretreatment with the NO synthase inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) or guanylyl cyclase inhibitor methylthionine chloride (MB) significantly inhibited vasodilation. An assessment of NO-related pathway protein expression revealed that GXNT enhanced the expression of phosphorylated endothelial NO synthase (eNOS) in a dose-dependent manner but had no effect on total eNOS, p-Akt, Akt, or PI3K levels in human umbilical vein ECs (HUVECs). In addition to PI3K/AKT signaling, Ca2+/calmodulin (CaM)-Ca2+/CaM-dependent protein kinase II (CaMKII) signaling is a major signal transduction pathway involved in eNOS activation in ECs. Further results showed that free calcium ion levels were decreased in HUVECs with GXNT treatment, accompanied by an increase in p-CaMKII expression, implying an increase in the Ca2+/CaM-Ca2+/CaMKII cascade. Taken together, these findings suggest that the GXNT may have exerted their vasodilative effect by activating the endothelial CaMKII/eNOS signaling pathway in endothelium-intact rings and calcium-related ion channels in endothelium-denuded vessels.

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The vasodilating effect of glucose differs among vessels at different branching level in the porcine retina ex vivo

Cited by 10 publications

References 42 publications

Reduced Oxygen Extraction in the Retinal Periphery When the Arterial Blood Pressure Is Increased by Isometric Exercise in Normal Persons

Reduced Oxygen Extraction in the Retinal Periphery When the Arterial Blood Pressure Is Increased by Isometric Exercise in Normal Persons

Differential Effects of Intra- and Extravascular ATP on the Diameter of Porcine Vessels at Different Branching Levels Ex Vivo

Vasodilatory Effect of Guanxinning Tablet on Rabbit Thoracic Aorta is Modulated by Both Endothelium-Dependent and -Independent Mechanism

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