Dataset Information

ATP-sensitive potassium (K(ATP)) channel openers diazoxide and nicorandil lower intraocular pressure in vivo.

ABSTRACT:

Purpose

To evaluate the expression of ATP-sensitive potassium (K(ATP)) channel subunits and study the effect of K(ATP) channel openers diazoxide and nicorandil on intraocular pressure (IOP) in an in vivo mouse model.

Methods

Expression of K(ATP) channel subunits in normal C57BL/6 mouse eyes was studied by immunohistochemistry and confocal microscopy. Wild-type C57BL/6 mice were treated with K(ATP) channel openers diazoxide (n = 10) and nicorandil (n = 10) for 14 days. Similar treatments with diazoxide were performed on K(ir)6.2((-/-)) mice (n = 10). IOP was recorded with a handheld tonometer 1 hour, 4 hours, and 23 hours following daily treatment. Posttreatment histology was examined by light and transmission electron microscopy.

Results

The K(ATP) channel subunits SUR2B, K(ir)6.1, and K(ir)6.2 were identified in all tissues within mouse eyes. Treatment with diazoxide in wild-type mice decreased IOP by 21.5 ± 3.2% with an absolute IOP reduction of 3.9 ± 0.6 mm Hg (P = 0.002). Nicorandil also decreased IOP (18.9 ± 1.8%) with an absolute IOP reduction of 3.4 ± 0.4 mm Hg (P = 0.002). Treatment with diazoxide in K(ir)6.2((-/-)) mice had no effect on IOP. No morphological abnormalities were observed in diazoxide- or nicorandil-treated eyes.

Conclusions

K(ATP) channel openers diazoxide and nicorandil are effective regulators of IOP in mouse eyes. K(ir)6.2 appears to be a major K(ATP) channel subunit through which IOP is lowered following treatment with diazoxide.

SUBMITTER: Chowdhury UR

PROVIDER: S-EPMC3720149 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Publications

ATP-sensitive potassium (K(ATP)) channel openers diazoxide and nicorandil lower intraocular pressure in vivo.

Chowdhury Uttio Roy UR Holman Bradley H BH Fautsch Michael P MP

Investigative ophthalmology & visual science 20130722 7

<h4>Purpose</h4>To evaluate the expression of ATP-sensitive potassium (K(ATP)) channel subunits and study the effect of K(ATP) channel openers diazoxide and nicorandil on intraocular pressure (IOP) in an in vivo mouse model.<h4>Methods</h4>Expression of K(ATP) channel subunits in normal C57BL/6 mouse eyes was studied by immunohistochemistry and confocal microscopy. Wild-type C57BL/6 mice were treated with K(ATP) channel openers diazoxide (n = 10) and nicorandil (n = 10) for 14 days. Similar trea ...[more]

PMID: 23778875

Similar Datasets

Project description:ATP-sensitive K+ (KATP) channel openers are vasodilators that activate both plasma membrane and mitochondrial KATP channels. Here, we investigated the molecular mechanisms by which diazoxide and pinacidil induce vasodilation by studying diameter regulation of wild-type [SUR2(+/+)] and sulfonylurea receptor (SUR) 2-deficient [SUR2(-/-)] mouse myogenic mesenteric arteries. Ryanodine (10 microM), a ryanodine-sensitive Ca2+ release (RyR) channel blocker; iberiotoxin (100 nM), a large-conductance Ca2+-activated K+ (KCa) channel blocker; 4-aminopyridine (4-AP; 1 mM), a voltage-gated K+ (KV) channel blocker; manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP; 100 microM), an antioxidant; and a combination of ryanodine and 4-AP reduced diazoxide (100 microM)-induced dilation in pressurized (60 mm Hg) SUR2(+/+) arteries by 45 to 77%. In contrast, these inhibitors did not alter pinacidil (5 microM)-induced dilation in SUR2(+/+) arteries. Reverse transcription-polymerase chain reaction indicated that SUR2B was the only SUR isoform expressed in SUR2(+/+) mesenteric artery smooth muscle cells, whereas SURs were absent in SUR2(-/-) cells. In SUR2(-/-) arteries, pinacidil-induced vasodilation was 10% of that in SUR2(+/+) arteries, whereas diazoxide-induced vasodilation was similar in SUR2(+/+) and SUR2(-/-) arteries. Atpenin (1 microM), a selective electron transport chain (ETC) complex II inhibitor, dilated arteries similarly to diazoxide, and this effect was attenuated by MnTMPyP and ryanodine + 4-AP. Atpenin also attenuated diazoxide-, but not pinacidil-induced vasodilation. In summary, data indicate that pinacidil-induced vasodilation requires SUR2B, whereas diazoxide-induced vasodilation does not require SURs. Rather, diazoxide-induced vasodilation involves ETCII inhibition; a smooth muscle cell-reactive oxygen species elevation; and RyR, KCa, and KV channel activation. These data indicate that KATP channel openers regulate arterial diameter via SUR-dependent and -independent pathways.

Dataset Information

ATP-sensitive potassium (K(ATP)) channel openers diazoxide and nicorandil lower intraocular pressure in vivo.

Purpose

Methods

Results

Conclusions

Publications

ATP-sensitive potassium (K(ATP)) channel openers diazoxide and nicorandil lower intraocular pressure in vivo.

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