Prenatal nicotine exposure induces gender-associated left ventricular-arterial uncoupling in adult offspring

Abstract

Abstract. Alterations in vascular or myocardial structure and function have been demonstrated in offspring subjected to prenatal nicotine exposure (PNE), however, limited data are available on how these changes interact. The present study assessed the hypothesis that prenatal nicotine exposure induced gender-specific alterations of left ventricular-arterial coupling indices in adult offspring. Female Sprague-Dawley rats were exposed to either nicotine (8 mg/kg/day) or saline via subcutaneous osmotic mini-pumps throughout gestation. Male and female offspring, aged 12 months, underwent non-invasive echocardiography and invasive left ventricular cannulation. Left ventricular-arterial coupling was analysed as the ratio of effective arterial elastance (Ea) to ventricular end-systolic elastance (Ees). The left ventricular myocardium and aorta were stained with hematoxylin and eosin and the myocardial cell cross-sectional area was calculated. Simultaneously, the ratio of medium thickness to internal diameter in the aorta and mesenteric artery was determined. The fibrosis component of left ventricle myocardium was analyzed by Sirius-red staining and further confirmed by hydroxyproline determination. The elastic properties of the aortic wall were analyzed by van Gieson staining. PNE caused significant increases in pulse pressure (56.36±7.41 vs. 50.16±4.94 mmHg; P<0.05) and left ventricular meridional wall stress (78.25±9.12 vs. 69.64±7.58 kdyne/cm 2 ; P<0.05) in male offspring compared with the control. Conversely, no similar effect was observed in female offspring. An elevated augmentation index was noted in male and female pups. Additionally, Ea/Ees was reduced in PNE males compared with control males, due to a disproportionate increase in Ees vs. Ea whereas in females, Ea/Ees did not differ significantly due to tandem increase in Ea and Ees. In addition, collagen cross-linking was markedly higher in male offspring, whereas it was unaltered in females compared with their respective controls. Fragmentation of the elastic network in the aorta and the increased ratio of medial thickness to internal diameter in the mesenteric artery were more evident in male offspring when compared with female offspring. PNE caused combined ventricular-arterial stiffening in male and female offspring, with lower Ea/Ees in males, while Ea/Ees was preserved in females. Enhanced collagen cross-linking in the myocardium, underdeveloped elastic fibers in the aorta and remodeled resistance vessels were associated with pathological ventricular arterial mismatching. The results of the present study indicated that male offspring were more susceptible to the development of ventricular and arterial dysfunction in response to PNE compared with female offspring.

Maternal nicotine exposure leads to decreased cardiac protein disulfide isomerase and impaired mitochondrial function in male rat offspring

“…Animal studies now demonstrate the strong links between perinatal nicotine exposure and long-term cardiac dysfunction (Chou & Chen, 2014;Fox et al, 2012;Gao et al, 2008;Lawrence et al, 2008;Wang et al, 2015;Xiao, Huang, Lawrence, Yang, & Zhang, 2007;Xiao et al, 2016;Yu et al, 2016). While several of these cardiac defects have been attributed to increased fibrosis, little is known about the underlying cellular stresses involved in nicotine-induced cardiac disease in these offspring, particularly after the perinatal nicotine insult (Chou & Chen, 2014;Yu et al, 2016).…”

“…While they are thought to be safer than conventional cigarettes, the long‐term health effects of early life exposure to nicotine remain elusive (De Long, Barra, Hardy, & Holloway, ). Regardless of its source, animal models have revealed that nicotine use during pregnancy leads to adverse metabolic, neurobehavioral, fertility, pulmonary and cardiovascular outcomes in the offspring (Chou & Chen, ; Dasgupta, Xiao, Xu, Yang, & Zhang, ; Gao et al, , ; Holloway, Kellenberger, & Petrik, ; Ma, Nicholson, Wong, Holloway, & Hardy, ; Pauly & Slotkin, ; Wang et al, ; Yu et al, ).…”

“…With respect to the postnatal cardiovascular health of the offspring, perinatal nicotine exposure results in a number of adverse cardiac outcomes including increased heart rate and blood pressure, thicker septum, decreased ejection volume, and a reduced ability to recover from ischemic insults (Fox et al, ; Gao et al, ; Lawrence et al, ; Xiao et al, ; Yu et al, ). Moreover, these offspring exhibit ventricular–arterial stiffening, underdeveloped elastic fibers and impaired acetylcholine‐induced aortic relaxation, with a greater incidence in males (Chou & Chen, ; Fox et al, ; Gao et al, ; Lawrence et al, ; Wang et al, ; Xiao et al, ; Yu et al, ). Elegant studies by Chou and Chen have demonstrated some of these heart deficits are due, in part, to nicotine‐induced cardiac remodeling (i.e.…”

“…greater incidence in males (Chou & Chen, 2014;Fox et al, 2012;Gao et al, 2008;Lawrence et al, 2008;Wang et al, 2015;Xiao et al, 2008;Yu et al, 2016). Elegant studies by Chou and Chen have demonstrated some of these heart deficits are due, in part, to nicotine-induced cardiac remodeling (i.e.…”

Gender peculiarities of coronary vessels tone and cardiac contractility disorders in the offspring of rats which underwent chronic stress during their pregnancy

“…Повышение жесткости миокарда левого желудочка у организмов, матери которых испытывали действие неблагоприятных факторов во время беременности (гипоксии, компонентов табачного дыма, высокого содержания поваренной соли в рационе и др.) уже доказано [13,14,15] и обусловлено активацией фибробластов в условиях окислительного стресса, а также дисбалансом цитокинов и факторов роста в развивающемся сердце плода. Одной из причин как систолической, так и диастолической дисфункции миокарда левого желудочка самцов, матери которых подвергались действию стрессоров во время беременности, может быть нарушение гомеостаза ионов кальция в кардиомиоцитах вследствие количественных и/или качественных изменений кальциевых каналов кардиомиоцитов.…”