Pregnancy and the endocrine regulation of the baroreceptor reflex

Abstract

-The purpose of this review is to delineate the general features of endocrine regulation of the baroreceptor reflex, as well as specific contributions during pregnancy. In contrast to the programmed changes in baroreflex function that occur in situations initiated by central command (e.g., exercise or stress), the complex endocrine milieu often associated with physiological and pathophysiological states can influence the central baroreflex neuronal circuitry via multiple sites and mechanisms, thereby producing varied changes in baroreflex function. During pregnancy, baroreflex gain is markedly attenuated, and at least two hormonal mechanisms contribute, each at different brain sites: increased levels of the neurosteroid 3␣-hydroxydihydroprogesterone (3␣-OH-DHP), acting in the rostral ventrolateral medulla (RVLM), and reduced actions of insulin in the forebrain. 3␣-OH-DHP appears to potentiate baroreflex-independent GABAergic inhibition of premotor neurons in the RVLM, which decreases the range of sympathetic nerve activity that can be elicited by changes in arterial pressure. In contrast, reductions in the levels or actions of insulin in the brain blunt baroreflex efferent responses to increments or decrements in arterial pressure. Although plasma levels of angiotensin II are increased in pregnancy, this is not responsible for the reduction in baroreflex gain, although it may contribute to the increased level of sympathetic nerve activity in this condition. How these different hormonal effects are integrated within the brain, as well as possible interactions with additional potential neuromodulators that influence baroreflex function during pregnancy and other physiological and pathophysiological states, remains to be clearly delineated.3␣-hydroxy-dihydroprogesterone; angiotensin II; insulin; paraventricular nucleus of the hypothalamus NORMAL PREGNANCY is characterized by profound changes in fluid and electrolyte balance and blood pressure regulation. Blood volume and cardiac output increase by 30 -50%, but arterial pressure falls due to even greater decreases in systemic vascular resistance (120,138,189). These hemodynamic alterations are evident early in pregnancy, precede the increases in uterine blood flow, and are sustained until parturition (127,138,189). Considerable data implicate increases in relaxin and nitric oxide (NO) in the systemic vasodilation induced by pregnancy (20,127,128,177,196). In addition, peripheral vascular sensitivity to circulating vasoconstrictors including vasopressin, angiotensin II (ANG II), and norepinephrine (NE) is decreased (50,71,154).Unlike the hemodynamic changes, which likely subserve adequate fetal development, an adverse consequence of normal pregnancy is a marked impairment of the arterial baroreceptor reflex. This change was first noted by Humphreys and Joels (97,98) in an extensive series of studies in anesthetized pregnant rabbits, in which reductions in carotid sinus pressure failed to elicit normal increases in arterial pressure and peripheral vascular resistanc...

GABA in the paraventricular nucleus tonically suppresses baroreflex function: alterations during pregnancy

“…First, ANG II is increased during pregnancy (3,30). Second, ANG II contributes to the increased basal levels of sympathetic activity in pregnant animals (24), indicating that angiotensin influences neural control of the circulation.…”

“…Pregnancy impairs baroreflex function by reducing baroreflex gain (BRG) and the maximum levels of sympathetic activity and HR achieved during acute severe hypotension (3). Yet, indirect evidence suggests that any PVN GABAergic suppressive influence on baroreflex function is lessened, thus counteracting the more primary inhibitory effect of pregnancy.…”

“…Yet, indirect evidence suggests that any PVN GABAergic suppressive influence on baroreflex function is lessened, thus counteracting the more primary inhibitory effect of pregnancy. First, pregnancy activates the renin-angiotensin system (3,30), which has been shown to decrease PVN GABAergic inhibition of sympathetic activity and heart rate (17,19,20). Second, a recent study by Kvochina et al (16) demonstrated that the increases in renal sympathetic nerve activity, HR, and arterial pressure following blockade of PVN GABA A receptors were less in anesthetized rats studied near term compared with nonpregnant animals.…”

Relaxin increases sympathetic nerve activity and activates spinally projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats

“…Z-Stack images (every 2 m) at a magnification of ϫ20 were obtained for brain regions of interest (ROIs): four rostral-caudal levels of the PVN, defined as levels [1][2][3][4], that contain the majority of AVP and spinally projecting cells (approximately Ϫ1.4 to Ϫ2.0 mm caudal to bregma) (1,61); the SON on either of the lateral edges of the optic tract (approximately Ϫ0.8 to 1.88 mm caudal to bregma); and the SFO (midline, approximately Ϫ0.8 to Ϫ1.4 mm caudal to bregma) (43). An Olympus BX51 with a disk-scanning unit (spinning disk), equipped with a three-axis motorized stage (Ludl Electronic Products, Hawthorne, NY), was used.…”

“…In pregnant (P) rats, the operating pressure range for arterial baroreflex control of sympathetic nerve activity (SNA) shifts toward the lower baseline arterial pressure (AP) of pregnancy, and baroreflex-mediated sympathoexcitation is attenuated (31), likely due to increased baroreflex-independent GABAergic inhibition of the rostral ventrolateral medulla (RVLM) in the brain stem (27). These adaptations are consistent with increased orthostatic hypotension in P women and greater sensitivity to the hypotensive effects of hemorrhage in pregnancy (3). However, even though the RVLM is under greater GABAergic inhibition, baseline SNA is elevated in conscious P rats (31) and women (17,20).…”