Submitted on May 14, 2008
Revised on June 17, 2008
Accepted on July 2, 2008
Metabolism and Synthesis of Arginine Vasopressin in Conscious Newborn Sheep
Darryl C. Miao1, Sithembiso C. Velaphi2, Timothy Roy1, Kevin DeSpain3, and Charles R. Rosenfeld4*
1 UT Southwestern Medical Center
2 University of Witwaterstrand
3 UT Southwestern Medical Center at Dallas
4 University of Texas Southwestern Medical Center
* To whom correspondence should be addressed. E-mail: charles.rosenfeld{at}utsouthwestern.edu.
Arginine vasopressin (AVP) is an important regulator of cardiovascular homeostasis in the fetus; but its role after birth is unclear. Although infused AVP increases mean arterial pressure (MAP) during the first month after birth, pressor responses are unchanged, suggesting vascular responsiveness is also unchanged. Alternatively, this could reflect increases in AVP metabolic clearance rate (MCRAVP). However, newborn AVP metabolism and synthesis are poorly studied. Therefore, we examined the pressor responses to infused AVP and the pattern of circulating AVP, AVP production rate (PRAVP) and MCRAVP in conscious newborn sheep (n=5) between 9-38d postnatal. Basal MAP rose and heart rate (HR) fell during the study period (P
0.02), while circulating AVP was unchanged (P>0.1), averaging 3.01±0.86 pg/ml. Infused AVP elicited steady-state responses at 10-40min, increasing plasma AVP and MAP and decreasing HR (P<0.001). Although pressor responses were unchanged between 9-38d, the rise in MAP correlated with increases in plasma AVP (R=0.47, P=0.02, n=24). MCRAVP was unchanged throughout the first month (P>0.2), averaging 205±17 ml/kg•min, and was associated with an elevated PRAVP, 973±267 pg/kg•min, that also was unchanged, P>0.1. After birth, both the MCRAVP and PRAVP are elevated, probably accounting for the stable plasma AVP levels observed. The former is also likely to account for the stable pressor responses to infused AVP during the first month of life. The reason for the elevated PRAVP is unclear; but may relate to increases in vascular volume associated with postnatal growth.
