Sex differences in vascular reactivity in mesenteric arteries from a mouse model of Acute Intermittent Porphyria [AIP]

Victor Pulgar; M. Yasuda; G. Lin; R. Desnick; H. Bonkovsky

Sex differences in vascular reactivity in mesenteric arteries from a mouse model of Acute Intermittent Porphyria [AIP]

Victor Pulgar, M. Yasuda, G. Lin, R. Desnick, H. Bonkovsky

Campbell University

Research output: Contribution to conference › Presentation

Abstract

<p> <h3 id="x-x-st0010"> Background and aims </h3> <p id="x-x-sp0045"> Acute intermittent <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/porphyria" title="Learn more about Porphyria from ScienceDirect's AI-generated Topic Pages"> porphyria </a> (AIP) results from a partial deficiency of <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/porphobilinogen-deaminase" title="Learn more about Porphobilinogen Deaminase from ScienceDirect's AI-generated Topic Pages"> porphobilinogen deaminase </a> (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 <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/c57bl-6-mouse" title="Learn more about C57BL 6 Mouse from ScienceDirect's AI-generated Topic Pages"> C57BL/6 mice </a> . <h3 id="x-x-st0015"> Methods </h3> <p id="x-x-sp0050"> An acute porphyric attack was induced in AIP mice by treatment with <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/phenobarbital" title="Learn more about Phenobarbital from ScienceDirect's AI-generated Topic Pages"> phenobarbital </a> . <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/blood-vessel-reactivity" title="Learn more about Blood Vessel Reactivity from ScienceDirect's AI-generated Topic Pages"> Vascular responses </a> to K <sup> + </sup> , <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/phenylephrine" title="Learn more about Phenylephrine from ScienceDirect's AI-generated Topic Pages"> phenylephrine </a> (PE), <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/acetylcholine" title="Learn more about Acetylcholine from ScienceDirect's AI-generated Topic Pages"> acetylcholine </a> (ACh), and hemin were determined (Wire Multi Myograph). <h3 id="x-x-st0020"> Results </h3> <p id="x-x-sp0055"> Maximal contraction to PE was increased in arteries from male and female AIP mice ( <em> p </em> < .05) during an induced attack of acute porphyria. Female AIP arteries had increased sensitivity to PE ( <em> p </em> < .05) even after <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/nitric-oxide" title="Learn more about Nitric Oxide from ScienceDirect's AI-generated Topic Pages"> nitric oxide </a> (NO) blockade with <em> N </em> <sub> ω </sub> -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). <h3 id="x-x-st0025"> Summary/conclusions </h3> <p id="x-x-sp0060"> 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. </p> </p> </p> </p></p>

Original language	American English
State	Published - Jan 1 2017
Event	ICPP2017 International Congress in Porphyrins and Porphyria - Bordeaux, France Duration: Jan 1 2017 → …

Conference

Conference	ICPP2017 International Congress in Porphyrins and Porphyria
Period	1/1/17 → …

Disciplines

Pharmacy and Pharmaceutical Sciences

Cite this

@conference{e2a4f4ca2891405a83b07a68b11ecc9d,

title = "Sex differences in vascular reactivity in mesenteric arteries from a mouse model of Acute Intermittent Porphyria [AIP]",

abstract = " 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 N ω -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. ",

author = "Victor Pulgar and M. Yasuda and G. Lin and R. Desnick and H. Bonkovsky",

year = "2017",

month = jan,

day = "1",

language = "American English",

note = "ICPP2017 International Congress in Porphyrins and Porphyria ; Conference date: 01-01-2017",

}

TY - CONF

T1 - Sex differences in vascular reactivity in mesenteric arteries from a mouse model of Acute Intermittent Porphyria [AIP]

AU - Pulgar, Victor

AU - Yasuda, M.

AU - Lin, G.

AU - Desnick, R.

AU - Bonkovsky, H.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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 N ω -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.

AB - 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 N ω -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.

UR - https://cufind.campbell.edu/pharmacy/2146

M3 - Presentation

T2 - ICPP2017 International Congress in Porphyrins and Porphyria

Y2 - 1 January 2017

ER -

Sex differences in vascular reactivity in mesenteric arteries from a mouse model of Acute Intermittent Porphyria [AIP]

Abstract

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