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Vasoconstrictor effect of aldosterone via angiotensin II type 1 (AT1) receptor: possible role of AT1 receptor dimerization.
Cardiovasc Res. 2008 Jul 01; 79(1):169-78.CR

Abstract

AIMS

We recently demonstrated that aldosterone induces a non-genomic vasoconstrictor effect on rat coronary arterioles and that this effect was blocked by angiotensin II type 1 receptor (AT1) blockers. Intracellular transglutaminase enhances AT1 signalling by cross-linking AT1 homodimers. The purpose of this study was to confirm the AT1-dependency of the vasoconstrictor effect of aldosterone using AT1a knockout (AT1aKO) mice and to investigate the role of intracellular transglutaminase and AT1 dimerization in this effect.

METHODS AND RESULTS

The mesenteric arterioles (60-160 microm) were isolated from C57BL/6J (wild-type, WT) and AT1aKO mice, and the internal diameter was measured by video microscopy. Aldosterone (10(-13) to 10(-6) M), but not hydrocortisone, produced a dose-dependent vasoconstriction in WT mice; the maximal diameter change was -8.6 +/- 0.3% from the baseline (P < 0.001). This vasoconstrictor effect was unaffected by the mineralocorticoid receptor antagonist spironolactone or eplerenone, the AT2 antagonist PD123319, the glucocorticoid receptor antagonist RU486, or endothelium denudation. Aldosterone's vasoconstrictor effect was negligible in AT1aKO mice. The AT1 blockers valsartan or candesartan suppressed aldosterone-induced vasoconstriction in WT mice. The transglutaminase inhibitors cystamine and monodansyl cadaverine also suppressed the vasoconstrictor effect of aldosterone, without affecting the vasoconstrictor effect of angiotensin II in WT mice. AT1 dimer protein levels were increased in WT mesenteric arterioles treated with 10(-7) M aldosterone, and the transglutaminase inhibitor and AT1 blocker blocked this aldosterone-induced formation of AT1 dimer. Treatment with 10(-7) M aldosterone for 10 min increased the transglutaminase activity by 2.5 +/- 0.2-fold in cultured vascular smooth muscle cells and by 1.2 +/- 0.1-fold in the mesenteric arterioles. These increases were abolished by transglutaminase inhibitors.

CONCLUSION

Aldosterone produces a non-genomic, endothelium-independent vasoconstrictor effect by enhancing intracellular transglutaminase activity and presumably inducing AT1 dimer formation in mesenteric arterioles.

Authors+Show Affiliations

Department of Cardiology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18326554

Citation

Yamada, Masahiro, et al. "Vasoconstrictor Effect of Aldosterone Via Angiotensin II Type 1 (AT1) Receptor: Possible Role of AT1 Receptor Dimerization." Cardiovascular Research, vol. 79, no. 1, 2008, pp. 169-78.
Yamada M, Kushibiki M, Osanai T, et al. Vasoconstrictor effect of aldosterone via angiotensin II type 1 (AT1) receptor: possible role of AT1 receptor dimerization. Cardiovasc Res. 2008;79(1):169-78.
Yamada, M., Kushibiki, M., Osanai, T., Tomita, H., & Okumura, K. (2008). Vasoconstrictor effect of aldosterone via angiotensin II type 1 (AT1) receptor: possible role of AT1 receptor dimerization. Cardiovascular Research, 79(1), 169-78. https://doi.org/10.1093/cvr/cvn064
Yamada M, et al. Vasoconstrictor Effect of Aldosterone Via Angiotensin II Type 1 (AT1) Receptor: Possible Role of AT1 Receptor Dimerization. Cardiovasc Res. 2008 Jul 1;79(1):169-78. PubMed PMID: 18326554.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vasoconstrictor effect of aldosterone via angiotensin II type 1 (AT1) receptor: possible role of AT1 receptor dimerization. AU - Yamada,Masahiro, AU - Kushibiki,Motoi, AU - Osanai,Tomohiro, AU - Tomita,Hirofumi, AU - Okumura,Ken, Y1 - 2008/03/07/ PY - 2008/3/11/pubmed PY - 2008/10/15/medline PY - 2008/3/11/entrez SP - 169 EP - 78 JF - Cardiovascular research JO - Cardiovasc Res VL - 79 IS - 1 N2 - AIMS: We recently demonstrated that aldosterone induces a non-genomic vasoconstrictor effect on rat coronary arterioles and that this effect was blocked by angiotensin II type 1 receptor (AT1) blockers. Intracellular transglutaminase enhances AT1 signalling by cross-linking AT1 homodimers. The purpose of this study was to confirm the AT1-dependency of the vasoconstrictor effect of aldosterone using AT1a knockout (AT1aKO) mice and to investigate the role of intracellular transglutaminase and AT1 dimerization in this effect. METHODS AND RESULTS: The mesenteric arterioles (60-160 microm) were isolated from C57BL/6J (wild-type, WT) and AT1aKO mice, and the internal diameter was measured by video microscopy. Aldosterone (10(-13) to 10(-6) M), but not hydrocortisone, produced a dose-dependent vasoconstriction in WT mice; the maximal diameter change was -8.6 +/- 0.3% from the baseline (P < 0.001). This vasoconstrictor effect was unaffected by the mineralocorticoid receptor antagonist spironolactone or eplerenone, the AT2 antagonist PD123319, the glucocorticoid receptor antagonist RU486, or endothelium denudation. Aldosterone's vasoconstrictor effect was negligible in AT1aKO mice. The AT1 blockers valsartan or candesartan suppressed aldosterone-induced vasoconstriction in WT mice. The transglutaminase inhibitors cystamine and monodansyl cadaverine also suppressed the vasoconstrictor effect of aldosterone, without affecting the vasoconstrictor effect of angiotensin II in WT mice. AT1 dimer protein levels were increased in WT mesenteric arterioles treated with 10(-7) M aldosterone, and the transglutaminase inhibitor and AT1 blocker blocked this aldosterone-induced formation of AT1 dimer. Treatment with 10(-7) M aldosterone for 10 min increased the transglutaminase activity by 2.5 +/- 0.2-fold in cultured vascular smooth muscle cells and by 1.2 +/- 0.1-fold in the mesenteric arterioles. These increases were abolished by transglutaminase inhibitors. CONCLUSION: Aldosterone produces a non-genomic, endothelium-independent vasoconstrictor effect by enhancing intracellular transglutaminase activity and presumably inducing AT1 dimer formation in mesenteric arterioles. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/18326554/Vasoconstrictor_effect_of_aldosterone_via_angiotensin_II_type_1__AT1__receptor:_possible_role_of_AT1_receptor_dimerization_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/cvn064 DB - PRIME DP - Unbound Medicine ER -