Prenatal Nicotine Exposure Results in the Inhibition of Baroreflex Sensitivity Induced by Intravenous Injection Angiotensin II in the Adult Male Offspring Rats

Abstract

Epidemiological studies show that maternal cigarette smoking is associated with an increased risk of cardiovascular diseases in postnatal life. Baroreflex sensitivity (BRS) is an important index for evaluating the homeostasis of the cardiovascular system. This experiment was designed to investigate the possible mechanism of prenatal nicotine on the adult male offspring's heart rate (HR) increase due to BRS. Pregnant rats received the 0.3 ml of saline or nicotine (1.5 mg kg) by subcutaneous injection from gestational days 3 to 21. The male offsprings of saline injected dams were the control group, and the male offsprings of the nicotine injected dams were the nicotine group. The 90-day-old male offsprings' funny current (I ) of their sinoatrial node (SAN) cells, BRS induced by intravenous injection of angiotensin (Ang) II in the presence or absence of the L-nitro-arginine methylester (L-NAME), cervical vagal activity, c-fos protein levels of the cervical spinal cord-8 to the thoracic spinal cord-5 (C-T) lateral horn neuron, and blood hormones were tested. The results showed that prenatal nicotine exposure had no effect on the offsprings' I of their SAN cells, but it significantly decreased the offsprings' BRS. The c-fos protein levels of the C-T lateral horn neurons and the blood catecholamine levels were increased in the nicotine group, but the cervical vagal activity was not changed. After intraventricular injection of L-NAME, the nicotine exposed offsprings' BRS was partly recovered. These data suggest that prenatal nicotine exposure results in hyper reactivity of the spinal sympathetic nerve center and a higher peripheral catecholamine hormone state of 90-day-old male offsprings, and these may be the reason for the BRS inhibition and HR increase. Nitric oxide (NO) may participate in the process acting as an important neurotransmitter.

Nicotine and the renin-angiotensin system

“…In rats with prior in utero nicotine exposure, a reduction of baroreflex sensitivity in response to ANG II infusion was observed (143,147). In addition, prenatal nicotine exposure increases blood norepinephrine levels at baseline as well as following intrave-R898 NICOTINE AND THE RAS nous administration of ANG II (147). Increased AT 1 R and decreased AT 2 R expression were observed in whole brain extracts from fetal and adult offspring rats that had been subjected to perinatal nicotine exposure (96).…”

“…Perinatal nicotine exposure alters the brain RAS and results in increased sympathetic activity in the adult offspring. In rats with prior in utero nicotine exposure, a reduction of baroreflex sensitivity in response to ANG II infusion was observed (143,147). In addition, prenatal nicotine exposure increases blood norepinephrine levels at baseline as well as following intrave-R898 NICOTINE AND THE RAS nous administration of ANG II (147).…”

Does Prenatal Exposure to CNS Stimulants Increase the Risk of Cardiovascular Disease in Adult Offspring?

“…Similar to cocaine (31, 33) and methamphetamine (27), rats that were prenatally exposed to nicotine also exhibit decreased expression of cardioprotective PKC-ε (72-74). Other investigators have reported increased heart rates, decreased contractile function (stroke volume, fractional shortening, and ejection fraction), fibrosis, and thickening of the left ventricular walls in adult rats following prenatal exposure to nicotine (62,63). These preclinical studies provide evidence that maternal use of tobacco increases the risk of ischemic injury, suppresses cardiac contractile function, and induces cardiac remodeling in adult offspring.…”

“…These nicotine-induced effects are associated with changes in the expression of angiotensin II receptors in vascular smooth muscle (60), increased thickening of the media of the arterial wall (60), enhanced sensitivity of vascular smooth muscle to calcium (60), increased oxidative stress (24, 59), attenuation of endothelium-dependent relaxation (24), and disruption of perivascular adipose-dependent mechanisms that regulate vascular tone (56,61). Attenuation of the baroceptor reflex and increased basal levels of circulating catecholamines and angiotensin II have also been reported in adult mice and rats following prenatal exposure to nicotine (58,60,62,63). Thus, prenatal nicotine may increase blood pressure through mechanisms that involve targets within the endothelium, vascular smooth muscle, and perivascular adventitia as well as mechanisms involving neuronal and hormonal regulation.…”

The Role of Smoking and Nicotine in the Transmission and Pathogenesis of COVID-19

“…Perinatal nicotine exposure is also demonstrated to alter the brain RAS resulting in enhanced sympathetic function in the adult offspring. Baroreflex sensitivity was decreased after Ang-II infusion in rats which were prenatally exposed to nicotine (Xiao et al, 2008;Yu et al, 2017). Perinatal nicotine exposure can also increase brain AT 1 R and decrease brain AT 2 R expression in offspring rats (Lu et al, 2008).…”