1: Hypertension. 2003 Jan;41(1):149-55. 

Heme oxygenase inhibitor restores arteriolar nitric oxide function in dahl rats.

Johnson FK, Durante W, Peyton KJ, Johnson RA.

Department of Physiology, Tulane University Health Sciences Center, New Orleans,
La 70112, USA. Fruzsi123@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,
Nomega-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.

PMID: 12511545 [PubMed - indexed for MEDLINE]