Abstract
Mean arterial pressure (MAP) increases after birth, however, the mechanisms remain unclear. Systemic angiotensin II (ANG II) infusions increase MAP in newborn sheep, but the direct effects of ANG II on peripheral vascular resistance (PVR) are minimal. Thus, its systemic pressor effects may reflect release of other pressor agents, e.g. α-agonists and/or AVP, suggesting they contribute to postnatal regulation of MAP and PVR. To address this, we performed studies in conscious sheep at 7–14, 15–21, and 22–35 d postnatal, infusing phenylephrine (PE) or AVP systemically or intra-arterially into the hindlimb while measuring MAP, heart rate (HR), and femoral blood flow (FmBF). Basal MAP and FmBF rose, whereas HR and femoral vascular resistance (FmVR) fell (p ≤ 0.03) during the first month postnatal. Although systemic PE and AVP dose dependently increased MAP and FmVR and decreased FmBF and HR (p < 0.001, ANOVA) at all ages, responses were not age dependent. Notably, increases in FmVR exceeded increases in MAP, and responses to PE appeared to exceed AVP (p < 0.05). Hindlimb infusions of both agents decreased FmBF and increased FmVR dose dependently (p < 0.001, ANOVA) at all ages without altering MAP or HR. These responses also were not age dependent. Unlike ANG II, PE and AVP directly increase PVR in newborn sheep. Moreover, FmVR increases more than MAP at all doses, suggesting these agonists may contribute to postnatal MAP regulation and could mediate the effects of systemic ANG II on postnatal MAP.
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Abbreviations
- ANG II:
-
angiotensin II
- AVP:
-
arginine vasopressin
- FmBF:
-
femoral blood flow
- FmVR:
-
femoral vascular resistance
- HR:
-
heart rate
- MAP:
-
mean arterial pressure
- PE:
-
phenylephrine
- PVR:
-
peripheral vascular resistance
- VSM:
-
vascular smooth muscle
References
Davidson D 1987 Circulating vasoactive substances and hemodynamic adjustments at birth in lambs. J Appl Physiol 63: 676–684
Assali NS 1967 Some aspects of fetal life in utero and the changes at birth. Am J Obstet Gynecol 97: 324–331
Chard T, Hudson CN, Edwards CR, Boyd NR 1971 Release of oxytocin and vasopressin by the human foetus during labour. Nature 234: 352–354
Hoppenstein JM, Miltenberger FW, Moran WH Jr 1968 The increase in blood levels of vasopressin in infants during birth and surgical procedures. Surg Gynecol Obstet 127: 966–974
Segar JL, Hajduczok G, Smith BA, Merrill DC, Robillard JE 1982 Ontogeny of baroreflex control of renal sympathetic nerve activity and heart rate. Am J Physiol 263: H1819–H1826
Klopfenstein HS, Rudolph AM 1978 Postnatal changes in the circulation and responses to volume loading in sheep. Circ Res 42: 839–845
Assali NS, Brinkman CR 3rd, Woods JR Jr, Dandavino A, Nuwayhid B 1977 Development of neurohumoral control of fetal, neonatal, and adult cardiovascular functions. Am J Obstet Gynecol 129: 748–759
LeFlore JL, Engle WD, Rosenfeld CR 2000 Determinants of blood pressure regulation in very low birth weight neonates: lack of effect of antenatal steroids. Early Hum Dev 59: 37–50
Engle WD 2001 Blood pressure in the very low birth weight neonate. Early Hum Dev 62: 97–130
Magness RR, Rosenfeld CR, Hassan A, Shaul PW 1996 Endothelial vasodilator production by uterine and systemic arteries. I. Effects of ANG II on PGI2 and NO in pregnancy. Am J Physiol 270: H1914–H1923
Yoshimura T, Rosenfeld CR, Magness RR 1991 Angiotensin II and α-agonist. III. In vitro fetal-maternal placental prostaglandins. Am J Physiol 260: E8–E13
Agata Y, Padbury JF, Ludlow JK, Polk DH, Humme JA 1986 The effect of chemical sympathectomy on catecholamine release at birth. Pediatr Res 20: 1338–1344
Cox BE, Rosenfeld CR 1999 Ontogeny of vascular angiotensin II receptor subtype expression in ovine development. Pediatr Res 45: 414–424
Arens Y, Chapados R, Cox BE, Kamm KE, Rosenfeld CR 1998 Differential development of umbilical and systemic arteries II. Contractile proteins. Am J Physiol 274: R1815–R1823
Woods JR Jr, Dandavino A, Brinkman CR 3rd, Nuwayhid B, Assali NS 1978 Cardiac output changes during neonatal growth. Am J Physiol 234: H520–H524
Wilson TA, Kaiser DL, Wright EM Jr, Ortt EM, Freedlender AE, Peach MJ, Carey RM 1981 Importance of plasma angiotensin concentrations in a comparative study of responses to angiotensin in the maturing newborn limb. Hypertension 3: II18–II24
Woods JR Jr, Dandavino A, Murayama K, Brinkman CR 3rd, Assali NS 1977 Autonomic control of cardiovascular functions during neonatal development and in adult sheep. Circ Res 40: 401–407
Rose JC, Morris M, Meis PJ 1982 Development aspects of pituitary and adrenal responses to arterial hypotension in neonatal, weanling, and adult sheep. Am J Physiol 242: E215–E219
Wiriyathian S, Porter JC, Naden RP, Rosenfeld CR 1983 Cardiovascular effects and clearance of arginine vasopressin in the fetal lamb. Am J Physiol 245: E24–E31
Wyse DG, Van Petten GR, Harris WH 1977 Responses to electrical stimulation, noradrenaline, serotonin, and vasopressin in the isolated ear artery of the developing lamb and ewe. Can J Physiol Pharmacol 55: 1001–1006
Velaphi SC, Roy T, DeSpain K, Rosenfeld CR 2002 Differential responses to systemic and local angiotensin II infusions in conscious postnatal sheep. Pediatr Res 52: 333–341
Wilson TA, Kaiser DL, Wright EM Jr, Peach MJ, Carey RM 1981 Ontogeny of blood pressure and the renin-angiotensin-aldosterone system: Sequential studies in newborn lamb. Circ Res 49: 416–423
Bottari SP, de Gaspero M, Steckelings UM, Levens NR 1993 Angiotensin II receptor subtypes: characterization, signalling mechanisms, and possible physiological implications. Front Neuroendocrinol 14: 123–171
Shi L, Hu F, Morrissey P, Yao J, Xu Z 2003 Intravenous angiotensin induces brain c-fos expression and vasopressin release in the near-term ovine fetus. Am J Physiol Endocrinol Metab 285: E1216–E1222
Cox BE, Williams CE, Rosenfeld CR 2000 Angiotensin II indirectly vasoconstricts the ovine uterine circulation. Am J Physiol Regul Integr Comp Physiol 278: R337–R344
Cox BE, Roy TA, Rosenfeld CR 2004 Angiotensin II mediates uterine vasoconstriction through alpha-stimulation. Am J Physiol Heart Circ Physiol 287: H126–H134
Nuwayhid B, Brinkman CR 3rd, Su C, Bevan JA, Assali NS 1975 Systemic and pulmonary hemodynamic responses to adrenergic and cholinergic agonists during fetal development. Biol Neonate 26: 301–317
Yoshimura T, Magness RR, Rosenfeld CR 1990 Angiotensin and α-agonist. I Responses of ovine fetoplacental vasculature. Am J Physiol 259: H464–H472
Naden RP, Rosenfeld CR 1981 Effect of angiotensin II on uterine and systemic vasculature in pregnant sheep. J Clin Invest 68: 468–474
Brans YW, Andrew DS, Schwartz CA, Carey KD 1991 Serial estimates of body water content and distribution during the first postnatal month in baboons. J Med Primatol 20: 75–81
Kaiser JR, Cox BE, Roy TA, Rosenfeld CR 1998 Differential development of umbilical and systemic arteries. I. ANG II receptor subtype expression. Am J Physiol 274: R797–R807
Minoura S, Gilbert RD 1987 Postnatal change of cardiac function in lambs: effects of ganglionic block and afterload. J Dev Physiol 9: 123–135
Segar JL 1997 Ontogeny of the arterial and cardiopulmonary baroreflex during fetal and postnatal life. Am J Physiol 273: R457–R471
Zugaib M, Forsythe AB, Nuwayhid B, Lieb SM, Tabsh K, Erkkola R, Ushioda E, Brinkman CR 3rd, Assali NS 1980 Mechanisms of beat-to-beat variability in the heart rate of the neonatal lamb. I. Influence of the autonomic nervous system. Am J Obstet Gynecol 138: 444–452
Levy MN, Zieske H 1969 Autonomic control of cardiac pacemaker activity and atrioventricular transmission. J Appl Physiol 27: 465–470
Nuyt AM, Segar JL, Holley AT, O'Mara MS, Chapleau MW, Robillard JE 1996 Arginine vasopressin modulation of arterial baroreflex responses in fetal and newborn sheep. Am J Physiol 271: R1643–R1653
Rosenfeld CR, Velaphi SC, DeSpain K, Roy T 2003 Changes in the renin-angiotensin system in the conscious postnatal sheep during the first month after birth. Pediatr Res 53: 146A
Rosenfeld CR 2001 Mechanisms regulating angiotensin II responsiveness by the uteroplacental circulation. Am J Physiol Regul Integr Comp Physiol 281: R1025–R1040
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Supported in part by the George L. MacGregor Professorship in Pediatrics and Grant HD-08783 from the National Institutes of Health.
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Velaphi, S., Roy, T., Despain, K. et al. Effects of Systemic and Local Phenylephrine and Arginine Vasopressin Infusions in Conscious Postnatal Sheep. Pediatr Res 58, 58–65 (2005). https://doi.org/10.1203/01.PDR.0000163395.07153.90
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DOI: https://doi.org/10.1203/01.PDR.0000163395.07153.90