1: Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1681-7. Epub 2003 Dec 23. 

Heme oxygenase-mediated endothelial dysfunction in DOCA-salt, but not in
spontaneously hypertensive, rat arterioles.

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

Tulane Hypertension and Renal Center of Excellence, Department of Physiology,
Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Fruzsi123@aol.com

Vascular heme oxygenase (HO) metabolizes heme to form carbon monoxide. Carbon
monoxide inhibits nitric oxide synthase and promotes endothelium-dependent
vasoconstriction. We reported HO-1-mediated endothelial dysfunction in Dahl
salt-sensitive hypertension. Previous studies suggested that salt-sensitive
hypertensive rats, but not spontaneously hypertensive rats (SHR), display
endothelial dysfunction. This study examines the hypothesis that HO-1-mediated
arteriolar endothelial dysfunction develops in deoxycorticosterone acetate
(DOCA)-salt hypertensive (DOCA) rats, but not in SHR. Uninephrectomized
(isoflurane anesthesia) male Sprague-Dawley rats received DOCA injections and
saline drinking solution for 4 wk. Rats subjected to sham surgery received
vehicle injections and tap water. Blood pressure was elevated in DOCA rats and
SHR compared with sham and Wistar-Kyoto (WKY) groups. Aortic HO-1 expression and
blood carboxyhemoglobin levels were elevated in the DOCA group, but not in SHR.
In isolated gracilis muscle arterioles, ACh caused concentration-related
vasodilation in all groups, with attenuated maximum responses in DOCA, but not
in SHR, arterioles. Acute pretreatment with an inhibitor of HO, chromium
mesoporphyrin, restored ACh-induced responses in DOCA arterioles to sham levels.
ACh responses remained the same in SHR and WKY arterioles after chromium
mesoporphyrin treatment. These data show that HO-1 levels and activity are
increased and arteriolar responses to ACh are decreased in DOCA rats, but not in
SHR. Furthermore, in DOCA arterioles, an inhibitor of HO restores ACh-induced
vasodilation to sham levels. These results suggest that elevated HO-1 levels and
activity, not resulting from hypertension per se, contribute to endothelial
dysfunction in DOCA rats.

PMID: 14693679 [PubMed - indexed for MEDLINE]