Myogenic tone and reactivity of rat ophthalmic artery in acute exposure to high glucose and in a type II diabetic model

Isamu Ito, Yagna P R Jarajapu, Dennis L. Guberski, Maria B. Grant, Harm J. Knot

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

PURPOSE. To evaluate the effect of acute exposure to high glucose on myogenic tone and reactivity of the rat ophthalmic artery and to compare the observations with that in ophthalmic artery from a diabetic rat model. METHODS. Ophthalmic arteries from Sprague-Dawley rats were pressurized at 70 mm Hg in an arteriograph, and outer diameter was monitored. Myogenic tone was assessed over a range of intraluminal pressures in the presence and absence of high glucose or mannitol. The effects of high glucose on reactivity to carbachol and phenylephrine were determined. Arteries from type II diabetic BBZDR/Wor rats and age-matched control rats were evaluated for myogenic tone and reactivity. RESULTS. Myogenic tone was enhanced by 25 mM, but decreased by 40 mM, glucose and was not affected by mannitol. Constriction to phenylephrine was not affected by 25 mM, but was decreased by 40 mM glucose, and carbachol-mediated dilation was unaffected. Effects of high glucose were not observed in the absence of endothelium. Miconazole, a nonselective inhibitor of cytochrome-P450 enzymes or dihydroouabain, an inhibitor of Na+,K+-ATPase blocked the effect of 40 mM but not 25 mM glucose. Arteries from diabetic rats showed decreased myogenic tone compared with control arteries, and this decrease was not observed in the absence of endothelium. CONCLUSIONS. Acute exposure to high glucose has a concentration- and endothelium-dependent effect on the myogenic tone of rat ophthalmic artery. Attenuation of tone by high glucose is probably due to the activation of smooth muscle Na+,K+-ATPase by endothelial cytochrome-P450 metabolite. Pressuremediated autoregulation in ophthalmic artery in type II diabetic BBZDR/Wor rat operates at lower resistance, probably due to hyperglycemia.

Original languageEnglish (US)
Pages (from-to)683-692
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume47
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

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Ophthalmic Artery
Glucose
Endothelium
Arteries
Carbachol
Mannitol
Phenylephrine
Cytochrome P-450 Enzyme System
Miconazole
Constriction
Hyperglycemia
Smooth Muscle
Sprague Dawley Rats
Dilatation
Homeostasis
Pressure

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Myogenic tone and reactivity of rat ophthalmic artery in acute exposure to high glucose and in a type II diabetic model. / Ito, Isamu; Jarajapu, Yagna P R; Guberski, Dennis L.; Grant, Maria B.; Knot, Harm J.

In: Investigative Ophthalmology and Visual Science, Vol. 47, No. 2, 02.2006, p. 683-692.

Research output: Contribution to journalArticle

Ito, Isamu ; Jarajapu, Yagna P R ; Guberski, Dennis L. ; Grant, Maria B. ; Knot, Harm J. / Myogenic tone and reactivity of rat ophthalmic artery in acute exposure to high glucose and in a type II diabetic model. In: Investigative Ophthalmology and Visual Science. 2006 ; Vol. 47, No. 2. pp. 683-692.
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T1 - Myogenic tone and reactivity of rat ophthalmic artery in acute exposure to high glucose and in a type II diabetic model

AU - Ito, Isamu

AU - Jarajapu, Yagna P R

AU - Guberski, Dennis L.

AU - Grant, Maria B.

AU - Knot, Harm J.

PY - 2006/2

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N2 - PURPOSE. To evaluate the effect of acute exposure to high glucose on myogenic tone and reactivity of the rat ophthalmic artery and to compare the observations with that in ophthalmic artery from a diabetic rat model. METHODS. Ophthalmic arteries from Sprague-Dawley rats were pressurized at 70 mm Hg in an arteriograph, and outer diameter was monitored. Myogenic tone was assessed over a range of intraluminal pressures in the presence and absence of high glucose or mannitol. The effects of high glucose on reactivity to carbachol and phenylephrine were determined. Arteries from type II diabetic BBZDR/Wor rats and age-matched control rats were evaluated for myogenic tone and reactivity. RESULTS. Myogenic tone was enhanced by 25 mM, but decreased by 40 mM, glucose and was not affected by mannitol. Constriction to phenylephrine was not affected by 25 mM, but was decreased by 40 mM glucose, and carbachol-mediated dilation was unaffected. Effects of high glucose were not observed in the absence of endothelium. Miconazole, a nonselective inhibitor of cytochrome-P450 enzymes or dihydroouabain, an inhibitor of Na+,K+-ATPase blocked the effect of 40 mM but not 25 mM glucose. Arteries from diabetic rats showed decreased myogenic tone compared with control arteries, and this decrease was not observed in the absence of endothelium. CONCLUSIONS. Acute exposure to high glucose has a concentration- and endothelium-dependent effect on the myogenic tone of rat ophthalmic artery. Attenuation of tone by high glucose is probably due to the activation of smooth muscle Na+,K+-ATPase by endothelial cytochrome-P450 metabolite. Pressuremediated autoregulation in ophthalmic artery in type II diabetic BBZDR/Wor rat operates at lower resistance, probably due to hyperglycemia.

AB - PURPOSE. To evaluate the effect of acute exposure to high glucose on myogenic tone and reactivity of the rat ophthalmic artery and to compare the observations with that in ophthalmic artery from a diabetic rat model. METHODS. Ophthalmic arteries from Sprague-Dawley rats were pressurized at 70 mm Hg in an arteriograph, and outer diameter was monitored. Myogenic tone was assessed over a range of intraluminal pressures in the presence and absence of high glucose or mannitol. The effects of high glucose on reactivity to carbachol and phenylephrine were determined. Arteries from type II diabetic BBZDR/Wor rats and age-matched control rats were evaluated for myogenic tone and reactivity. RESULTS. Myogenic tone was enhanced by 25 mM, but decreased by 40 mM, glucose and was not affected by mannitol. Constriction to phenylephrine was not affected by 25 mM, but was decreased by 40 mM glucose, and carbachol-mediated dilation was unaffected. Effects of high glucose were not observed in the absence of endothelium. Miconazole, a nonselective inhibitor of cytochrome-P450 enzymes or dihydroouabain, an inhibitor of Na+,K+-ATPase blocked the effect of 40 mM but not 25 mM glucose. Arteries from diabetic rats showed decreased myogenic tone compared with control arteries, and this decrease was not observed in the absence of endothelium. CONCLUSIONS. Acute exposure to high glucose has a concentration- and endothelium-dependent effect on the myogenic tone of rat ophthalmic artery. Attenuation of tone by high glucose is probably due to the activation of smooth muscle Na+,K+-ATPase by endothelial cytochrome-P450 metabolite. Pressuremediated autoregulation in ophthalmic artery in type II diabetic BBZDR/Wor rat operates at lower resistance, probably due to hyperglycemia.

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