The Effects of Salt Loading on the Renin-Angiotensin Control of Blood Pressure in the Newborn Lamb

Abstract

SummaryThe renin-angiotensin system control of newborn blood pressure was studied in six sets of twin newborn lambs. The mean aortic blood pressure and plasma renin activity (PRA) was 79.6 f 0.96 mmHg (mean and S.E.) and 6.88 + 0.83 ng/ml/h in the chronically salt-loaded lambs (10 mEq/kg/day for 5 days); 86.16 + 1.8 mmHg ( P < 0.001) and 20.48 f 2.46 ng/ml/h ( P < 0.001), respectively in the control lambs. PRA and % change after angiotensin 11 blockade with saralasin was greater in the control lambs, 181.5 2 6.09 ng/ml/h and 780% than in the chronically salt-loaded lambs, 40 f 10.47 and 480%, P < 0.001. Blood pressure decreased 10 mmHg only in the control lambs, P < 0.001. An angiotensin 11 dose of 0.25 pg/kg/min increased blood pressure 32 + 3.1 mmHg in control mambs, and 0.10 pg/kg/min increased blood pressure 32 + 3.2 mmHg in acutely salt-loaded (10 mEq/kg in 20 ml 5% dextrose/water) lambs. PRA and mean aortic blood pressure decreased in the acutely salt-loaded lambs from 22.3 + 3.0 ng/ml/ h and86.6 f 1.0mmHg to 11.3 f 1.1 and76.4 f 0.8, P < 0.01, respectively. These data show that sodium loading will suppress the basal renin-angiotensin system levels, and mean aortic blood pressure; decrease the hypotensive and PRA responses to saralasin; and increase the pressor responsiveness to angiotensin 11. Abbreviations D/W, dextrose/water PRA, plasma renin activity Blood pressure is under volume and vasoconstrictive control. In the normal newborn lamb, basal blood pressure is maintained under the vasoconstrictor control of the renin-angiotensin system (19). Pressor responsiveness to angiotensin 11 is decreased compared to the ewe (18). These altered responses may be secondary to the very high renin-angiotensin levels present in the newborn lamb (20).Blood pressure control and the renin-angiotensin system are both affected by sodium (8, 10, 11). The purpose of this study was to determine the effects of acute and chronic salt loading on the renin-angiotensin system and blood pressure control in the newborn lamb. MATERIALS AND METHODSSix sets of twin newborn lambs 7-14 days (7-9 kg) and 14-21 days (11-13 kg) were studied for each experiment. The nursing lambs with their mothers were obtained from the vivarium. Polyvinyl catheters were inserted into the femoral artery and vein under local anesthetic (1% lidocaine). The animals were restrained on a specially constructed board, so that they were nonstressed and warm, and studied 2 days after catheter placement. Experiment 1. NaCl(10 mEq/kg in 20 ml5% D/W) was infused over 60 rnin in one of each set of twin lambs 7-14 days of age.Serial doses of angiotensin 11 (0.025, 0.5, 0.1, and 0.25 yg/kg/ min) were infused for 15 rnin each into the salt-loaded and control lambs. Blood samples for PRA were drawn before and 55 and 60 rnin after the NaCl infusion. Mean aortic blood pressure was monitored continuously.Experiment 2. NaC1 (10 mEq/kg/day in 50 ml 5% D/W) was infused slowly over 2 h for 5 days @to one of each set of twin lambs 14-21 days of age. On the 5th day, two baseline bl...

Renin-angiotensin II response to the hemodynamic pathology of ovines with ventricular septal defect.

“…PRA is elevated in the infant, presumably in response to the relative sodium-wasting state, 27 and the subsequent generation of angiotensin II becomes a dominant factor in maintaining systemic resistance. 12 Stimulation of the renin-angiotensin system results in a hyposensitivity to additional exogenous angiotensin II.…”

“…2730 The normal suckling lamb would receive 1-2 meq Na + /kg/day, whereas lambs in this study received 4 meq Na + /kg/day or at least twice the normal sodium intake. 27 It appears that the RAS is near maximally stimulated with a large VSD since both maximal pharmacologic doses of angiotensin II and a threefold stimulation of PRA with furosemide caused only an additional 20% increase in R,. If the RAS system was down regulated in terms of organ receptor response, the recovery must be short (10 minutes) since short-term inhibition of angiotensin II production with captopril restores responsiveness to exogenous angiotensin II.…”