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Vascular dysfunctio...
Vascular dysfunction in obese diabetic db/db mice involves the interplay between aldosterone/mineralocorticoid receptor and Rho kinase signaling
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- Cat, Aurelie Nguyen Dinh (author)
- Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
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- Callera, Glaucia E. (author)
- Univ Ottawa, Ottawa Hosp, Res Inst, Kidney Res Ctr, Ottawa, ON, Canada.
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- Friederich, Malou, 1983- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland
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- Sanchez, Ana (author)
- Univ Complutense, Fac Farm, Dept Fisiol, Madrid, Spain.
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- Dulak-Lis, Maria Gabriela (author)
- Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
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- Tsiropoulou, Sofia (author)
- Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
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- Montezano, Augusto C. (author)
- Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
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- He, Ying (author)
- Univ Ottawa, Ottawa Hosp, Res Inst, Kidney Res Ctr, Ottawa, ON, Canada.
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- Briones, Ana M. (author)
- Univ Autonoma Madrid, CIBER Enfermedades Cardiovasc, Sch Med, Dept Pharmacol, Madrid, Spain.
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- Jaisser, Frederic (author)
- Ctr Rech Cordeliers, INSERM Team 1 1138, Paris, France.
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- Touyz, Rhian M. (author)
- Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.;Univ Ottawa, Ottawa Hosp, Res Inst, Kidney Res Ctr, Ottawa, ON, Canada.
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Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland Univ Ottawa, Ottawa Hosp, Res Inst, Kidney Res Ctr, Ottawa, ON, Canada. (creator_code:org_t)
- 2018-02-13
- 2018
- English.
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In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Abstract
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- Activation of aldosterone/mineralocorticoid receptors (MR) has been implicated in vascular dysfunction of diabetes. Underlying mechanisms are elusive. Therefore, we investigated the role of Rho kinase (ROCK) in aldosterone/MR signaling and vascular dysfunction in a model of diabetes. Diabetic obese mice (db/db) and control counterparts (db/+) were treated with MR antagonist (MRA, potassium canrenoate, 30 mg/kg/day, 4 weeks) or ROCK inhibitor, fasudil (30 mg/kg/day, 3 weeks). Plasma aldosterone was increased in db/db versus db/+. This was associated with enhanced vascular MR signaling. Norepinephrine (NE)-induced contraction was increased in arteries from db/db mice. These responses were attenuated in mice treated with canrenoate or fasudil. Db/db mice displayed hypertrophic remodeling and increased arterial stiffness, improved by MR blockade. Vascular calcium sensitivity was similar between depolarized arteries from db/+ and db/db. Vascular hypercontractility in db/db mice was associated with increased myosin light chain phosphorylation and reduced expression of PKG-1 alpha. Vascular RhoA/ROCK signaling and expression of pro-inflammatory and pro-fibrotic markers were exaggerated in db/db mice, effects that were attenuated by MRA. Fasudil, but not MRA, improved vascular insulin sensitivity in db/db mice, evidenced by normalization of Irs1 phosphorylation. Our data identify novel pathways involving MR-RhoA/ROCK-PKG-1 that underlie vascular dysfunction and injury in diabetic mice.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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Cat, Aurelie Ngu ...
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Callera, Glaucia ...
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Friederich, Malo ...
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Sanchez, Ana
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Dulak-Lis, Maria ...
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Tsiropoulou, Sof ...
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Montezano, Augus ...
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He, Ying
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Briones, Ana M.
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Jaisser, Frederi ...
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Touyz, Rhian M.
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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Uppsala University