Published Online
on July 5, 2005

A more recent version of this article appeared on July 12, 2005

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Submitted on August 10, 2004
Revised on January 4, 2005
Accepted on March 11, 2005

Glucose-6 Phosphate Dehydrogenase Deficiency Decreases the Vascular Response to Angiotensin II

Reiko Matsui MD^*, Shanqin Xu MD, MS, Karlene A. Maitland BS, Antoinette Hayes BS, Jane A. Leopold MD, Diane E. Handy PhD, Joseph Loscalzo MD, PhD, and Richard A. Cohen MD

From the Vascular Biology Unit, Whitaker Cardiovascular Institute and Evans Department of Medicine, Boston University School of Medicine, Boston, Mass.

^* To whom correspondence should be addressed. E-mail: rmatsui{at}bu.edu.

Background--Glucose-6-phosphate dehydrogenase (G6PD) regulates production of the reduced form of NADPH through the pentose phosphate pathway. G6PD may therefore affect superoxide anion production via vascular NADPH oxidase, which is key in mediating the vascular response to angiotensin II (Ang II). We determined the hypertensive and vascular hypertrophic response to Ang II in G6PD-deficient mice.

Methods and Results--Ang II (0.7 mg/kg per day) was infused via subcutaneous osmotic pumps for 6 days in male hemizygote G6PD mutant (G6PD^mut) and wild-type (WT) C3H mice. (1) Compared with WT, G6PD^mut mouse aorta had 10% to 20% of G6PD activity and 50% less NADPH. (2) Basal systolic blood pressure was not significantly different in G6PD^mut mice (WT 88±4 mm Hg versus G6PD^mut 95±4 mm Hg), but Ang II increased blood pressure to a lower level in G6PD^mut mice (WT 139±4 mm Hg versus G6PD^mut 123±5 mm Hg; P<0.05). (3) Ang II increased aortic medial thickness less in G6PD^mut mice (WT 71±2 µm versus G6PD^mut 62±1 µm; P<0.01). (4) 3-o-Nitrotyrosine staining and dihydroethidium oxidation in the aorta was increased by Ang II less in G6PD^mut mice. (5) Smooth muscle cells isolated from G6PD^mut mice showed less Ang II-induced phosphorylation of Akt and p42/44 ERK.

Conclusions--G6PD deficiency may reduce vascular superoxide anion production by limiting production of the substrate for NADPH oxidase, thereby inhibiting oxidant-mediated Ang II-induced signaling pathways that contribute to hypertension and smooth muscle hypertrophy.

Key words: angiotensin • aorta • free radicals • hypertension • hypertrophy

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