1. Heme oxygenase-derived carbon monoxide promotes arteriolar endothelial dysfunction and contributes to salt-induced hypertension in Dahl salt-sensitive rats.
- Author
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Teran FJ, Johnson RA, Stevenson BK, Peyton KJ, Jackson KE, Appleton SD, Durante W, and Johnson FK
- Subjects
- Acetylcholine pharmacology, Animals, Arterioles drug effects, Arterioles enzymology, Blood Pressure drug effects, Endothelium, Vascular drug effects, Endothelium, Vascular enzymology, Enzyme Inhibitors pharmacology, Heme Oxygenase (Decyclizing) antagonists & inhibitors, Hypertension chemically induced, Hypertension enzymology, In Vitro Techniques, Male, Mesoporphyrins pharmacology, Muscle, Skeletal blood supply, Rats, Rats, Inbred Dahl, Regional Blood Flow, Sodium Chloride, Dietary administration & dosage, Time Factors, Vasodilation drug effects, Vasodilator Agents pharmacology, Arterioles physiopathology, Carbon Monoxide metabolism, Endothelium, Vascular physiopathology, Heme Oxygenase (Decyclizing) metabolism, Hypertension physiopathology
- Abstract
Vascular tissues express heme oxygenase (HO), which metabolizes heme to form carbon monoxide (CO). Heme-derived CO inhibits nitric oxide synthase and promotes endothelium-dependent vasoconstriction. After 4 wk of high-salt diet, Dahl salt-sensitive (Dahl-S) rats display hypertension, increased vascular HO-1 expression, and attenuated vasodilator responses to ACh that can be completely restored by acute treatment with an inhibitor of HO. In this study, we examined the temporal development of HO-mediated endothelial dysfunction in isolated pressurized first-order gracilis muscle arterioles, identified the HO product responsible, and studied the blood pressure effects of HO inhibition in Dahl-S rats on a high-salt diet. Male Dahl-S rats (5-6 wk) were placed on high-salt (8% NaCl) or low-salt (0.3% NaCl) diets for 0-4 wk. Blood pressure increased gradually, and responses to an endothelium-dependent vasodilator, ACh, decreased gradually with the length of high-salt diet. Flow-induced dilation was abolished in hypertensive Dahl-S rats. Acute in vitro pretreatment with an inhibitor of HO, chromium mesoporphyrin (CrMP), restored endothelium-dependent vasodilation and abolished the differences between groups. The HO product CO prevented the restoration of endothelium-dependent dilation by CrMP. Furthermore, administration of an HO inhibitor lowered blood pressure in Dahl-S rats with salt-induced hypertension but did not do so in low-salt control rats. These results suggest that hypertension and HO-mediated endothelial dysfunction develop gradually and simultaneously in Dahl-S rats on high-salt diets. They also suggest that HO-derived CO underlies the impaired endothelial dysfunction and contributes to hypertension in Dahl-S rats on high-salt diets.
- Published
- 2005
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