An analysis of the DOCA-salt model of hypertension in HO-1-/- mice and the Gunn rat.
Heme oxygenase-1 (HO-1) is induced in the vasculature in the DOCA-salt model of hypertension in rats. Whereas the HO system and its products may exert vasodilator effects, recent studies have suggested that the HO system may predispose to hypertension. The present study examined the effects of selected components of the HO system, specifically, the HO-1 isozyme and the product bilirubin in the DOCA-salt model of systemic hypertension; the experimental approach employed mutant rodent models, namely, the HO-1(-/-) mouse and the hyperbilirubinemic Gunn rat. DOCA-salt induced HO-1 protein in the aorta in HO-1(+/+) mice and provoked a significant rise in systolic arterial pressure in HO-1(-/-) mice but not in HO-1(+/+) mice; this effect could not be ascribed to impaired urinary sodium excretion or impaired glomerular filtration rate in the DOCA-salt-treated HO-1(-/-) mice. The administration of DOCA salt to uninephrectomized rats significantly increased systolic arterial pressure in wild-type rats, an effect that was attenuated in the mutant Gunn rat; this reduction in systemic hypertension in the DOCA-salt-treated Gunn rat was not due to a greater induction of HO-1 in the vasculature or to a more avid urinary sodium excretion. DOCA-salt impaired endothelium-dependent and endothelium-independent vasorelaxation in wild-type rats but not in Gunn rats; prior exposure to bilirubin repaired the defect in endothelium-dependent vasorelaxation in aortic rings in DOCA-salt-treated rats. DOCA salt stimulated vascular production of superoxide anion in wild-type but not in Gunn rats. We suggest that HO-1 and the product bilirubin may exert a countervailing effect in the DOCA-salt model of systemic hypertension.
Nath
Karl A
KA
Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. nath.karl@mayo.edu
d'Uscio
Livius V
LV
Juncos
Julio P
JP
Croatt
Anthony J
AJ
Manriquez
Melissa C
MC
Pittock
Siobhan T
ST
Katusic
Zvonimir S
ZS
D000818:Animals; D001663:Bilirubin / Q000378:metabolism*; D001794:Blood Pressure; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D011911:Rats, Gunn; D017208:Rats, Wistar; D012965:Sodium Chloride; D013045:Species Specificity
D003900:Desoxycorticosterone; D012965:Sodium Chloride; D051547:Heme Oxygenase-1; D001663:Bilirubin