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Published on: December 14, 2014
Prenatal Exposure to Methamphetamine Causes Vascular Dysfunction in Adult Male Rat Offspring
Hasitha Chavva1, Adam M Belcher1, Daniel A Brazeau1,2
1Department of Pharmaceutical Sciences, Marshall University School of Pharmacy, Huntington, WV, United States.
Insights
Prenatal methamphetamine exposure alters adult offspring vascular function, particularly in males. This may increase the risk of cardiovascular disorders later in life.
Area of Science:
- Cardiovascular Science
- Developmental Toxicology
- Pharmacology
Background:
- Prenatal methamphetamine exposure is linked to adverse offspring outcomes, primarily behavioral and neurological.
- Limited research exists on the long-term cardiovascular effects of fetal methamphetamine exposure.
Purpose of the Study:
- To investigate the impact of chronic fetal methamphetamine exposure on adult offspring vascular function.
- To determine if prenatal methamphetamine exposure sex-dependently affects vascular responses in adult rats.
Main Methods:
- Pregnant rats received daily methamphetamine or saline injections throughout gestation.
- Vascular function, including relaxation and contraction, was assessed in 5-month-old offspring aortas and mesenteric arteries.
- Responses to acetylcholine, nitroprusside, angiotensin II, serotonin, and phenylephrine were evaluated with and without perivascular adipose tissue (PVAT).
Main Results:
- Prenatal methamphetamine impaired acetylcholine-induced relaxation in male aortas with intact PVAT, an effect absent in females or when PVAT was removed.
- Angiotensin II-induced contractions were potentiated in male aortas regardless of PVAT, an effect reversed by L-NAME.
- No significant effects were observed on nitroprusside-induced relaxation, serotonin/phenylephrine contractions, mesenteric artery function, or basal blood pressure.
Conclusions:
- Prenatal methamphetamine exposure sex-dependently alters adult vascular function, specifically affecting vasodilation and vasoconstriction mechanisms.
- These alterations may contribute to an increased risk of developing adult vascular disorders following prenatal methamphetamine exposure.
Abstract:
Methamphetamine use during pregnancy can have negative consequences on the offspring. However, most studies investigating the impact of prenatal exposure to methamphetamine have focused on behavioral and neurological outcomes. Relatively little is known regarding the impact of prenatal methamphetamine on the adult cardiovascular system. This study investigated the impact of chronic fetal exposure to methamphetamine on vascular function in adult offspring. Pregnant female rats received daily saline or methamphetamine (5 mg/kg) injections starting on gestational day 1 and continuing until the pups were born. Vascular function was assessed in 5 month old offspring. Prenatal methamphetamine significantly decreased both the efficacy and potency of acetylcholine-induced relaxation in isolated male (but not female) aortas when perivascular adipose tissue (PVAT) remained intact. However, prenatal methamphetamine had no impact on acetylcholine-induced relaxation when PVAT was removed. Nitroprusside-induced relaxation of the aorta was unaffected by prenatal methamphetamine. Angiotensin II-induced contractile responses were significantly potentiated in male (but not female) aortas regardless of the presence of PVAT. This effect was reversed by L-nitro arginine methyl ester (L-NAME). Serotonin- and phenylephrine-induced contraction were unaffected by prenatal methamphetamine. Prenatal methamphetamine had no impact on acetylcholine-induced relaxation of third order mesenteric arteries and no effect on basal blood pressure. These data provide evidence that prenatal exposure to methamphetamine sex-dependently alters vasomotor function in the vasculature and may increase the risk of developing vascular disorders later in adult life.
