(702.1) Sex-Dependent Changes in Vascular Function in Adult Rats Following Prenatal Exposure to Methamphetamine
Monday, April 4, 2022
10:00 AM – 12:00 PM
Location: Exhibit/Poster Hall A-B - Pennsylvania Convention Center
Poster Board Number: B154
Hasitha Chavva (Marshall University School of Pharmacy), Adam Belcher (Marshall University School of Pharmacy), Daniel Brazeau (Marshall University School of Pharmacy, Marshall University School of Medicine), Boyd Rorabaugh (Marshall University School of Pharmacy, Marshall University School of Medicine)
Presenting Author Marshall University School of Pharmacy
Background: Prenatal exposure to central nervous system stimulants such as cocaine, nicotine, and caffeine alters cardiovascular function in adult offspring. Methamphetamine use during pregnancy is associated with negative consequences in the offspring. However, most studies of methamphetamine use during pregnancy have focused on behavioral and neurological outcomes. Relatively little is known regarding the impact of prenatal methamphetamine exposure on the adult cardiovascular system. This study examined the hypothesis that methamphetamine use during pregnancy alters contractile function of the vasculature in the adult offspring. We also investigated the role of perivascular adipose tissue (PVAT) in methamphetamine-induced changes in vascular function.
Methods: Pregnant female rats received daily injections of saline or methamphetamine (5 mg/kg) throughout gestation. Agonist-induced contraction and relaxation responses were measured in aortas of 5 month old offspring in the presence and absence of perivascular adipose tissue.
Results: Prenatal methamphetamine significantly attenuated acetylcholine-induced relaxation in male (but not female) aortas when PVAT remained intact. However, prenatal methamphetamine had no impact on acetylcholine-induced relaxation when PVAT was removed. Nitroprusside-induced relaxation was unaffected by prenatal methamphetamine. Prenatal exposure to methamphetamine had no impact on acetylcholine-induced relaxation in third order mesenteric arteries of male or female offspring regardless of the presence of PVAT. Angiotensin II-induced contractile responses were significantly potentiated in male (but not female) aortas regardless of the presence of PVAT. This effect was abolished by L-Nitro arginine methyl ester (L-NAME). Contractile responses to phenylephrine and serotonin were unaffected in both male and female aortas. Basal blood pressure in adult male and female offspring was also unaffected by prenatal exposure to methamphetamine.
Conclusions: Prenatal exposure to methamphetamine sex-dependently alters PVAT function in the aorta. Methamphetamine also enhances angiotensin II-induced contraction through a mechanism that involves suppression of nitric oxide signaling. These data provide evidence that methamphetamine use during pregnancy induces sex-dependent changes in the vasculature that may increase the risk of cardiovascular disease in adult offspring.
