Chronic captopril treatment reveals the role of ANG II in cardiovascular function of embryonic American alligators (Alligator mississippiensis)

Abstract

Angiotensin II (ANG II) is a powerful vasoconstrictor of the renin-angiotensin system (RAS) that plays an important role in cardiovascular regulation in adult and developing vertebrates. Knowledge of ANG II's contribution to developmental cardiovascular function comes from studies in fetal mammals and embryonic chickens. This is the first study to examine the role of ANG II in cardiovascular control in an embryonic reptile, the American alligator (Alligator mississippiensis). Using chronic low (~ 5-mg kg embryo), or high doses (~ 450-mg kg embryo) of captopril, an angiotensin-converting enzyme (ACE) inhibitor, we disrupted the RAS and examined the influence of ANG II in cardiovascular function at 90% of embryonic development. Compared to embryos injected with saline, mean arterial pressure (MAP) was significantly reduced by 41 and 72% under low- and high-dose captopril treatments, respectively, a greater decrease in MAP than observed in other developing vertebrates following ACE inhibition. Acute exogenous ANG II injection produced a stronger hypertensive response in low-dose captopril-treated embryos compared to saline injection embryos. However, ACE inhibition with the low dose of captopril did not change adrenergic tone, and the ANG II response did not include an α-adrenergic component. Despite decreased MAP that caused a left shifted baroreflex curve for low-dose captopril embryos, ANG II did not influence baroreflex sensitivity. This study demonstrates that ANG II contributes to cardiovascular function in a developing reptile, and that the RAS contributes to arterial blood pressure maintenance during development across multiple vertebrate groups.

Genome of the Komodo dragon reveals adaptations in the cardiovascular and chemosensory systems of monitor lizards

“…In mammals, the level of Angll increases in response to intense physical activity, contributing to arterial blood pressure and regional blood regulation 63 – 66 . Reptiles have a functional renin-angiotensin system (RAS) that is important for their cardiovascular response to aerobic activity 67 – 69 . The positive selection for AGT points to important adaptations in cardiovascular physiology and the renin-angiotensin system in the Komodo dragon.…”

A high-resolution, chromosome-assigned Komodo dragon genome reveals adaptations in the cardiovascular, muscular, and chemosensory systems of monitor lizards

“…The positive selection for AGT points to important adaptations in these physiological parameters. Reptiles have a functional renin-angiotensin system that is important for their cardiovascular physiology 39–41 . It is likely that positive selection for AGT is related to a mammalian-like cardiovascular function in the Komodo dragon.…”

Changes in hemoglobin function and isoform expression during embryonic development in the American alligator, Alligator mississippiensis

“…Plasticity of the embryonic cardiovascular system in crocodilians has been the focus of several recent investigations. The American alligator (Alligator mississippiensis; Duadin, 1801) undergoes both morphological and physiological changes in response to fluctuations in O 2 availability during development (8,9,(11)(12)(13)(14)(15)(16). Specifically, egg incubation in 10% O 2 induces changes in protein composition of cardiac tissue, cardiac growth, blood pressure, and cardiovascular regulatory mechanisms of embryonic alligators (14,15,(17)(18)(19)(20).…”