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Effect of Prenatal Methamphetamine Exposure on Blood Pressure and Vascular Function in Adult Male and Female Offspring
Author(s) -
Harrison Allison M.,
Seeley Sarah L.,
Rorabaugh Boyd R.,
Chrissobolis Sophocles
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.997.3
Subject(s) - offspring , meth , methamphetamine , blood pressure , medicine , endocrinology , pregnancy , physiology , biology , chemistry , genetics , monomer , organic chemistry , acrylate , polymer
Hypertension and endothelial dysfunction are commonly associated with cardiovascular disease. Methamphetamine (meth) use is a widespread societal problem, with ~4.7% of the US population having tried meth at least once. Meth use during pregnancy can have deleterious developmental and behavioral consequences for offspring, including delayed development of gross motor skills and decreased memory. Although prenatal meth exposure reportedly causes increased cardiac ischemia in females, there exists very little additional data on the cardiovascular consequences of prenatal meth exposure in adult offspring. The aims of this study were to therefore test whether prenatal meth exposure increases blood pressure and impairs endothelial function in adult offspring, and whether this is influenced by gender. Pregnant female Sprague Dawley rats (8 wk old) were treated with either saline or methamphetamine (5 mg/kg/d sc , once daily) from gestational day 1 until pups were born. Male and female pups were weaned at 3 weeks of age and blood pressure (using tail cuff plethysmography) and vascular function (using myography) assessed after rats were 8 weeks old. Systolic blood pressure (SBP) was increased in male offspring prenatally exposed to meth (SBP = 151±2 mmHg, n=11) vs saline (141±3 mmHg, n=11, P<0.05 vs meth). SBP was similar in female offspring prenatally exposed to meth (SBP = 128±5 mmHg, n=7) and saline (SBP = 125±4 mmHg, n=8, P>0.05 vs meth). In males, endothelium‐dependent relaxation (assessed via relaxation responses to acetylcholine [ACh]) in second‐order mesenteric resistance arteries was impaired by prenatal meth exposure (pEC50: meth‐exposed = −7.5±0.06, n=5; saline‐exposed = −8.0±0.1, n=6; P<0.05). Prenatal meth exposure had no effect on responses to ACh in females (pEC50: meth‐exposed = −7.8±0.05, n=5; saline‐exposed = −8.1±0.08, n=5; P>0.05). Vasorelaxation responses to the endothelium‐independent agonist DEA NONOate, and phenylephrine‐induced vasoconstriction were not influenced by prenatal meth exposure in either gender. These data suggest that prenatal exposure to methamphetamine increases blood pressure and causes endothelial dysfunction in adult male offspring, whereas female offspring prenatally exposed to methamphetamine are protected against an increase in blood pressure and endothelial dysfunction. Prenatal methamphetamine exposure may therefore increase risk of cardiovascular disease in males. Support or Funding Information Raabe College of Pharmacy, Ohio Northern University