Endothelial Cell Tetrahydrobiopterin Modulates Sensitivity to Ang (Angiotensin) II-Induced Vascular Remodeling, Blood Pressure, and Abdominal Aortic Aneurysm

Hypertension
Surawee ChuaiphichaiGillian Douglas

Abstract

GTPCH (GTP cyclohydrolase 1, encoded by Gch1) is required for the synthesis of tetrahydrobiopterin; a critical regulator of endothelial NO synthase function. We have previously shown that mice with selective loss of Gch1 in endothelial cells have mild vascular dysfunction, but the consequences of endothelial cell tetrahydrobiopterin deficiency in vascular disease pathogenesis are unknown. We investigated the pathological consequence of Ang (angiotensin) II infusion in endothelial cell Gch1 deficient (Gch1 fl/fl Tie2cre) mice. Ang II (0.4 mg/kg per day, delivered by osmotic minipump) caused a significant decrease in circulating tetrahydrobiopterin levels in Gch1 fl/fl Tie2cre mice and a significant increase in the Nω-nitro-L-arginine methyl ester inhabitable production of H2O2 in the aorta. Chronic treatment with this subpressor dose of Ang II resulted in a significant increase in blood pressure only in Gch1 fl/fl Tie2cre mice. This finding was mirrored with acute administration of Ang II, where increased sensitivity to Ang II was observed at both pressor and subpressor doses. Chronic Ang II infusion in Gch1 fl/fl Tie2ce mice resulted in vascular dysfunction in resistance mesenteric arteries with an enhanced constrictor and ...Continue Reading

References

Jun 1, 1995·Journal of Hypertension·M J BlackG R Campbell
Jun 1, 1995·American Journal of Hypertension·G SimonG Cserep
Apr 13, 2004·Journal of Hypertension·Agostino VirdisErnesto L Schiffrin
Sep 4, 2004·American Journal of Physiology. Heart and Circulatory Physiology·David S WeberKathy K Griendling
Apr 13, 2005·Circulation·Jeffrey P KhooKeith M Channon
Jun 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Karel Chalupsky, Hua Cai
Mar 17, 2010·The Journal of Biological Chemistry·Motohiro NishidaHitoshi Kurose
Nov 16, 2010·Current Opinion in Nephrology and Hypertension·Johannes Stegbauer, Thomas M Coffman
Aug 21, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Ioannis ParastatidisW Robert Taylor
Apr 24, 2014·Journal of the American Heart Association·Keyvan Karimi GalougahiGemma A Figtree
May 6, 2015·The Canadian Journal of Cardiology·Augusto C MontezanoRhian M Touyz
Jan 28, 2016·Clinical Science·Theophilus I EmetoJonathan Golledge
Jan 6, 2017·American Journal of Physiology. Renal Physiology·Manuel ThiemeJohannes Stegbauer

❮ Previous
Next ❯

Citations

Dec 4, 2019·Hypertension·Anna F Dominiczak, Trudie J Meyer
Nov 7, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Lihong PanYong Ji
May 29, 2020·Journal of Cellular and Molecular Medicine·Han SuJian-Xiong Chen
Aug 13, 2020·Scientific Reports·Maria Del Carmen Asensio LopezDomingo A Pascual Figal
Aug 13, 2020·Biomedicines·Jessica GambardellaValentina Trimarco

❮ Previous
Next ❯

Methods Mentioned

BETA
coronary artery bypass

Software Mentioned

GraphPad Prism

Related Concepts

Related Feeds

Aneurysm

Aneurysms are outward distensions or bulges that occurs in a weakened wall of blood vessels. Discover the latest research on aneurysms here.

Aortic Aneurysm

An aortic aneurysm is the weakening and bulging of the blood vessel wall in the aorta. This causes dilatation of the aorta, which is usually asymptomatic but carries the risk of rupture and hemorrhage. Find the latest research on aortic aneurysms here.