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(Hypertension. 2003;41:149.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Heme Oxygenase Inhibitor Restores Arteriolar Nitric Oxide Function in Dahl Rats

From the Department of Physiology, Tulane University Health Sciences Center (F.K.J., R.A.J.), New Orleans, La; and Houston VA Medical Center and Departments of Medicine and Pharmacology, Baylor College of Medicine (W.D., K.J.P.), Houston, Tex.

Correspondence to Fruzsina K. Johnson, MD, Department of Physiology, Tulane University Health Sciences Center, 1430 Tulane Ave, SL39, New Orleans, LA 70112. E-mail Fruzsi123{at}aol.com

Vascular tissues express heme oxygenase (HO), which metabolizes heme to form carbon monoxide (CO). CO relaxes vascular smooth muscle but inhibits nitric oxide (NO) formation. Decreased NO synthesis may contribute to salt-induced hypertension in Dahl salt-sensitive (DS) rats. The current study examines the hypothesis that elevated levels of endogenous CO contribute to NO dysfunction in salt-induced hypertensive DS rats. Male DS rats were placed on high-salt (8% NaCl, HS) or low-salt (0.3% NaCl, LS) diets for 4 weeks. With respect to the LS group, the HS group’s blood pressure and carboxyhemoglobin levels were elevated, and abdominal aortas showed 6-fold higher HO-1 protein levels. Experiments used isolated pressurized first-order gracilis muscle arterioles superfused with oxygenated modified Krebs buffer. An inhibitor of NO synthase, N-nitro-L-arginine methyl ester (L-NAME), caused concentration-dependent vasoconstriction in both groups, with attenuated responses in HS arterioles. HS arterioles also showed attenuated vasodilatory responses to an endothelium-dependent vasodilator, acetylcholine. Acute pretreatment with an inhibitor of HO, chromium mesoporphyrin, enhanced vascular responses to L-NAME and acetylcholine in both groups but abolished the differences between HS and LS arterioles. These data show that HO-1 protein levels and CO production are increased in HS rats. Arteriolar responses to L-NAME and acetylcholine are impaired in HS rats compared with LS animals, and this difference can be abolished by an inhibitor of endogenous CO production. These results suggest that elevated levels of endogenous CO contribute to arteriolar NO dysfunction in DS rats with salt-induced hypertension.

Key Words: acetylcholine • nitric oxide • hypertension, sodium-dependent • rats, Dahl • endothelium

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