Enhanced heme oxygenase-mediated coronary vasodilation in Dahl salt-sensitive hypertension.
BACKGROUND
Cardiovascular tissues express heme oxygenase (HO), which metabolizes heme to form carbon monoxide (CO). Carbon monoxide promotes relaxation of coronary vascular smooth muscle. Increased HO-1 expression provides cardioprotection during certain pathologic conditions. On a high salt (HS) diet Dahl salt-sensitive (DS) rats develop hypertension that is accompanied by left ventricular hypertrophy, whereas Dahl salt-resistant rats (DR) do not. This study tests the hypothesis that cardiac HO-1 expression is increased in DS rats with salt-induced hypertension and provides cardioprotection by promoting coronary vasodilation.


METHODS
Male DS and DR rats were placed on a HS (8% NaCl) or low salt (LS, 0.3% NaCl) diet for 4 weeks. Cardiac HO isoform expression were determined by immunohistochemistry. Experiments used isolated paced Langendorff-hearts perfused at a constant flow. Changes in coronary perfusion pressure and left ventricular contractility (dP/dt(max)) were measured in response to an inhibitor of HO, chromium mesoporphyrin (CrMP).


RESULTS
With respect to the LS group, DS rats on HS diet showed elevated mean arterial pressure and increased heart weight. Coronary arterial HO-1 immunostaining was enhanced in HS rats, but HO-2 staining was similar in both groups. In isolated Langendorff-hearts the HO inhibitor CrMP increased coronary perfusion pressure and calculated coronary resistance, and decreased left ventricular contractility (dP/dt(max)) in both groups, but the response was exaggerated in HS rat hearts. In the DR strain, HS diet did not augment CrMP responses and had no effect on any of the parameters measured with respect to the LS diet.


CONCLUSIONS
These findings suggest that coronary HO-1 expression is increased to promote enhanced coronary vasodilation in DS rats with salt-induced hypertension.
Johnson
Robert A
RA
Department of Physiology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA. RobertJ393@aol.com
Teran
Federico J
FJ
Durante
William
W
Peyton
Kelly J
KJ
Johnson
Fruzsina K
FK
D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D006339:Heart Rate; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D012982:Sodium, Dietary / Q000009:adverse effects*; D014664:Vasodilation / Q000502:physiology*
D012982:Sodium, Dietary; D006419:Heme Oxygenase (Decyclizing)