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Sex differences in vascular reactivity in mesenteric arteries from a mouse model of acute intermittent porphyria.
Pulgar, Victor M; Yasuda, Makiko; Gan, Lin; Desnick, Robert J; Bonkovsky, Herbert L.
Afiliación
  • Pulgar VM; Department of Pharmaceutical Sciences, Campbell University, Buies Creek, NC, USA; Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC, USA. Electronic address: pulgar@campbell.edu.
  • Yasuda M; Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA. Electronic address: makiko.yasuda@mssm.edu.
  • Gan L; Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA. Electronic address: lin.gan@mssm.edu.
  • Desnick RJ; Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA. Electronic address: robert.desnick@mssm.edu.
  • Bonkovsky HL; Section on Gastroenterology & Hepatology, Wake Forest University/NC Baptist Medical Center, Winston-Salem, NC, USA. Electronic address: hbonkovs@wakehealth.edu.
Mol Genet Metab ; 128(3): 376-381, 2019 11.
Article en En | MEDLINE | ID: mdl-30639047
BACKGROUND AND AIMS: Acute intermittent porphyria (AIP) results from a partial deficiency of porphobilinogen deaminase (PBGD). Symptomatic AIP patients, most of whom are women, experience acute attacks characterized by severe abdominal pain and abrupt increases in blood pressure. Here, we characterized the reactivity of mesenteric arteries from male and female AIP mice with ~30% of normal PBGD activity and wild type C57BL/6 mice. METHODS: An acute porphyric attack was induced in AIP mice by treatment with phenobarbital. Vascular responses to K+, phenylephrine (PE), acetylcholine (ACh), and hemin were determined (Wire Multi Myograph). RESULTS: Maximal contraction to PE was increased in arteries from male and female AIP mice (p < .05) during an induced attack of acute porphyria. Female AIP arteries had increased sensitivity to PE (p < .05) even after nitric oxide (NO) blockade with Nω-nitro-L-arginine methyl ester (L-NAME) (p < .05). Maximal relaxation to ACh was similar in males and females with lower sensitivity in female AIP arteries (p < .05). Hemin induced greater relaxation in AIP arteries in both males and females (p < .05). SUMMARY/CONCLUSIONS: Sex differences in this AIP mouse model include a pro-contractile response in females. These alterations may contribute to the increased blood pressure during an acute attack and provide a novel mechanism of action whereby heme ameliorates the attacks.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores Sexuales / Porfiria Intermitente Aguda / Arterias Mesentéricas Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Mol Genet Metab Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA / METABOLISMO Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores Sexuales / Porfiria Intermitente Aguda / Arterias Mesentéricas Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Mol Genet Metab Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA / METABOLISMO Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos