Sex-specific effects of heme oxygenase-2 deficiency on renovascular hypertension.
BACKGROUND
Heme oxygenase-2 (HO-2) is the main isoform responsible for the breakdown of heme and release of carbon monoxide in the vasculature. Vascular-derived carbon monoxide protects against excessive vasoconstriction due to agents such as angiotensin II (Ang II) and in states of deficiency of nitric oxide. The current study was designed to determine the role of HO-2 in the development of renovascular hypertension using HO-2 knockout mice.


METHODS
Polyurethane cuffs were placed around the left renal artery of male and female HO-2 wild-type (WT), heterozygous (HET), and knockout (KO) mice between 16 and 24 weeks of age to induce renovascular hypertension. After 3 weeks, blood pressure was measured for 5 days, after which time both clipped and unclipped kidneys were harvested.


RESULTS
No differences were observed in the blood pressure of sham mice between the different genotypes of both sexes. Cuffing of the left renal artery resulted in a significant increase in blood pressure in all genotypes of both sexes. In male mice, the increase in blood pressure was significantly greater in HET and KO mice as compared to WT mice (P < .05). This effect was not observed in female mice. Renovascular hypertension resulted in a significant increase (P < .05) in cardiac hypertrophy in male mice, which was not different between the genotypes. In female mice, HET and KO mice exhibited significantly greater (P < .05) cardiac hypertrophy as compared with WT mice.


CONCLUSION
These results demonstrate a sex-specific effect of HO-2 deficiency on the development of renovascular hypertension and its effects on the heart in response to the increase in blood pressure.
['Stout|Jacob M|JM|', 'Gousset|Monette U|MU|', 'Drummond|Heather A|HA|', 'Gray|Will|W|', 'Pruett|Brandon E|BE|', 'Stec|David E|DE|']
D000804:Angiotensin II D000818:Animals D001663:Bilirubin D001794:Blood Pressure D002248:Carbon Monoxide D006332:Cardiomegaly D059865:Endoplasmic Reticulum Stress D005260:Female D006419:Heme Oxygenase (Decyclizing) D006579:Heterozygote D006977:Hypertension, Renal D008297:Male D051379:Mice D057507:Mice, 129 Strain D008810:Mice, Inbred C57BL D018345:Mice, Knockout D012083:Renin D012084:Renin-Angiotensin System D012727:Sex Characteristics D014661:Vasoconstriction
carbon monoxide Angiotensin II blood pressure bilirubin renin