RESUMO
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.
Assuntos
Pressão Sanguínea/genética , Heme Oxigenase (Desciclizante)/genética , Hipertensão Renal/genética , Hipertensão Renal/fisiopatologia , Caracteres Sexuais , Angiotensina II/sangue , Animais , Bilirrubina/sangue , Monóxido de Carbono/sangue , Cardiomegalia/genética , Cardiomegalia/fisiopatologia , Estresse do Retículo Endoplasmático/genética , Estresse do Retículo Endoplasmático/imunologia , Feminino , Heme Oxigenase (Desciclizante)/deficiência , Heterozigoto , Hipertensão Renal/imunologia , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Renina/sangue , Sistema Renina-Angiotensina/genética , Sistema Renina-Angiotensina/imunologia , Vasoconstrição/fisiologiaRESUMO
New guidance on the prevention and management of pressure ulcers has been developed collaboratively by the National Institute for Health and Clinical Excellence (NICE) and the Royal College of Nursing. Julie Stevens and Will Gray provide the background to its development and discuss the key recommendations.
