Epigenetic Upregulation of Carotid Body Angiotensin Signaling Increases Blood Pressure

Epigenetic changes can be shaped by a wide array of environmental cues, maternal health, and behaviors. One of the most detrimental behaviors to the developing fetus is nicotine exposure. Perinatal nicotine exposure remains a significant risk factor for cardiovascular health and, in particular, hypertension. Increased basal carotid body (CB) activity and excitation are significant contributors to hypertension. This study investigated the epigenetic changes to CB activity induced by perinatal nicotine exposure resulting in CB-mediated hypertension.

We used a rodent model of perinatal nicotine exposure and cell culture methods.

We show that the AgtR1 (angiotensin II type 1 receptor) is upregulated in the carotid bodies of nicotine-exposed offspring. These changes were attributed to an upregulation of genetic promotion as DNA methylation of AgtR1 occurred within intron regions, exemplifying an upregulation of genetic transcription for this gene. Nicotine increased angiotensin signaling in vitro. CB reactivity to angiotensin was increased in perinatal nicotine-exposed offspring compared with control offspring. Furthermore, CB denervation reduced arterial pressure because of suppressed efferent sympathetic activity in perinatal nicotine-exposed offspring.

Our data demonstrate that perinatal nicotine exposure adversely affects CB afferent sensing, which augments efferent sympathetic activity to increase vasoconstrictor signaling and induce hypertension. Targeting angiotensin signaling in the carotid bodies may provide a way to alleviate hypertension acquired by adverse maternal uterine environments in general and perinatal nicotine exposure in particular.