Impaired β-adrenergic hyperpolarization in arteries from prehypertensive spontaneously hypertensive rats

Kenichi Goto, Koji Fujii, Isao Abe

研究成果: ジャーナルへの寄稿記事

15 引用 (Scopus)

抄録

Stimulation of β-adrenoceptors leads to vascular smooth muscle hyperpolarization, presumably through the β-adrenoceptors/Gs protein/adenylate cyclase/ATP-sensitive K+-channels (KATP) signaling cascade, which may play an important role in the sympathetic control of membrane potential. β-Adrenoceptor-mediated hyperpolarization has been shown to be impaired in the established stage of experimental hypertension. The present study tested the hypothesis that β-adrenergic hyperpolarization may be defective before the development of hypertension in some forms of genetic hypertension. We evaluated β-adrenoceptor-mediated hyperpolarization using microelectrodes in mesenteric resistance arteries from 5-week-old, prehypertensive, spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Isoproterenol-induced hyperpolarization was significantly smaller in SHR than in WKY (10-7 mol/L: -4.6±0.6 versus -7.8±0.8 mV, P<0.01: 10-6 mol/L: -7.8±0.5 versus -9.8±0.6 mV, P<0.05: n=9). Furthermore, hyperpolarization to cholera toxin, a direct activator of Gs protein, was also impaired in SHR. On the other hand, hyperpolarization to forskolin, an adenylate cyclase activator, and to levcromakalim, a KATP opener, was comparable between groups. These findings suggest that β-adrenoceptor-mediated hyperpolarization is defective in SHR before the development of hypertension, presumably because of an abnormality at the Gs protein site. Considering the importance of membrane potential in the control of vascular tone, altered β-adrenergic control of membrane potential might play a role in the development of hypertension in SHR.

元の言語英語
ページ(範囲)609-613
ページ数5
ジャーナルHypertension
37
発行部数2 II
出版物ステータス出版済み - 3 19 2001

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Inbred SHR Rats
Adrenergic Agents
Adrenergic Receptors
Arteries
Hypertension
Membrane Potentials
Inbred WKY Rats
Adenylyl Cyclases
Cromakalim
KATP Channels
Proteins
Mesenteric Arteries
Cholera Toxin
Microelectrodes
Colforsin
Vascular Smooth Muscle
Isoproterenol
Blood Vessels
Adenosine Triphosphate

All Science Journal Classification (ASJC) codes

  • Internal Medicine

これを引用

Impaired β-adrenergic hyperpolarization in arteries from prehypertensive spontaneously hypertensive rats. / Goto, Kenichi; Fujii, Koji; Abe, Isao.

:: Hypertension, 巻 37, 番号 2 II, 19.03.2001, p. 609-613.

研究成果: ジャーナルへの寄稿記事

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abstract = "Stimulation of β-adrenoceptors leads to vascular smooth muscle hyperpolarization, presumably through the β-adrenoceptors/Gs protein/adenylate cyclase/ATP-sensitive K+-channels (KATP) signaling cascade, which may play an important role in the sympathetic control of membrane potential. β-Adrenoceptor-mediated hyperpolarization has been shown to be impaired in the established stage of experimental hypertension. The present study tested the hypothesis that β-adrenergic hyperpolarization may be defective before the development of hypertension in some forms of genetic hypertension. We evaluated β-adrenoceptor-mediated hyperpolarization using microelectrodes in mesenteric resistance arteries from 5-week-old, prehypertensive, spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Isoproterenol-induced hyperpolarization was significantly smaller in SHR than in WKY (10-7 mol/L: -4.6±0.6 versus -7.8±0.8 mV, P<0.01: 10-6 mol/L: -7.8±0.5 versus -9.8±0.6 mV, P<0.05: n=9). Furthermore, hyperpolarization to cholera toxin, a direct activator of Gs protein, was also impaired in SHR. On the other hand, hyperpolarization to forskolin, an adenylate cyclase activator, and to levcromakalim, a KATP opener, was comparable between groups. These findings suggest that β-adrenoceptor-mediated hyperpolarization is defective in SHR before the development of hypertension, presumably because of an abnormality at the Gs protein site. Considering the importance of membrane potential in the control of vascular tone, altered β-adrenergic control of membrane potential might play a role in the development of hypertension in SHR.",
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AU - Fujii, Koji

AU - Abe, Isao

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N2 - Stimulation of β-adrenoceptors leads to vascular smooth muscle hyperpolarization, presumably through the β-adrenoceptors/Gs protein/adenylate cyclase/ATP-sensitive K+-channels (KATP) signaling cascade, which may play an important role in the sympathetic control of membrane potential. β-Adrenoceptor-mediated hyperpolarization has been shown to be impaired in the established stage of experimental hypertension. The present study tested the hypothesis that β-adrenergic hyperpolarization may be defective before the development of hypertension in some forms of genetic hypertension. We evaluated β-adrenoceptor-mediated hyperpolarization using microelectrodes in mesenteric resistance arteries from 5-week-old, prehypertensive, spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Isoproterenol-induced hyperpolarization was significantly smaller in SHR than in WKY (10-7 mol/L: -4.6±0.6 versus -7.8±0.8 mV, P<0.01: 10-6 mol/L: -7.8±0.5 versus -9.8±0.6 mV, P<0.05: n=9). Furthermore, hyperpolarization to cholera toxin, a direct activator of Gs protein, was also impaired in SHR. On the other hand, hyperpolarization to forskolin, an adenylate cyclase activator, and to levcromakalim, a KATP opener, was comparable between groups. These findings suggest that β-adrenoceptor-mediated hyperpolarization is defective in SHR before the development of hypertension, presumably because of an abnormality at the Gs protein site. Considering the importance of membrane potential in the control of vascular tone, altered β-adrenergic control of membrane potential might play a role in the development of hypertension in SHR.

AB - Stimulation of β-adrenoceptors leads to vascular smooth muscle hyperpolarization, presumably through the β-adrenoceptors/Gs protein/adenylate cyclase/ATP-sensitive K+-channels (KATP) signaling cascade, which may play an important role in the sympathetic control of membrane potential. β-Adrenoceptor-mediated hyperpolarization has been shown to be impaired in the established stage of experimental hypertension. The present study tested the hypothesis that β-adrenergic hyperpolarization may be defective before the development of hypertension in some forms of genetic hypertension. We evaluated β-adrenoceptor-mediated hyperpolarization using microelectrodes in mesenteric resistance arteries from 5-week-old, prehypertensive, spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Isoproterenol-induced hyperpolarization was significantly smaller in SHR than in WKY (10-7 mol/L: -4.6±0.6 versus -7.8±0.8 mV, P<0.01: 10-6 mol/L: -7.8±0.5 versus -9.8±0.6 mV, P<0.05: n=9). Furthermore, hyperpolarization to cholera toxin, a direct activator of Gs protein, was also impaired in SHR. On the other hand, hyperpolarization to forskolin, an adenylate cyclase activator, and to levcromakalim, a KATP opener, was comparable between groups. These findings suggest that β-adrenoceptor-mediated hyperpolarization is defective in SHR before the development of hypertension, presumably because of an abnormality at the Gs protein site. Considering the importance of membrane potential in the control of vascular tone, altered β-adrenergic control of membrane potential might play a role in the development of hypertension in SHR.

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