Organ tissue blood flow responses to hypoxemia in lambs: effect of angiotensin converting enzyme inhibitor.

Abstract

Summary: Chronically-catheterized lambs (n = 21), 2–38 days of age, were studied to test the hypothesis that the products of angiotensin converting enzyme (ACE) activity are involved in control of baseline arterial pressure and organ tissue blood flow and the redistribution of organ tissue blood flow in response to normocapnic hypoxemia in the maturing lamb. ACE activity was inhibited by administration of captopril [2.5 μg/(kg ± min)], which significantly (P < 0.01) decreased arterial concentrations (mean ± S.D.) of angiotensin-II (from 105.0 ± 33.9 to 67.0 ± 25.9 pg/ml) and aldosterone (from 115.0 ± 105.0 to 53.8 ± 28.6 pg/ml) and inhibited by greater than 90% the vasopressor response to an intravenous bolus of angiotensin-I (1 μg/kg). Baseline mean arterial pressure was significantly (P < 0.01) decreased from 78 ± 8 to 66 ± 10 mmHg) and remained depressed during hypoxemia (67 ± 12 mmHg) and recovery (62 ± 9 mmHg) periods. Baseline heart rate was unchanged by ACE inhibition (from 181 ± 33 to 188 ± 35 beats/min) but increased (P < 0.01) significantly in response to hypoxemia (to 233 ± 52 beats/min). Baseline heart, adrenal, jejunum, ileum, and skeletal muscle tissue blood flow, measured by radiolabeled microspheres, were not significantly (P > 0.05) changed by ACE inhibitor. Baseline liver tissue blood flow increased slightly [from 0.10 ± 0.10 to 0.16 ± 0.12 ml/(min ± g)] but significantly (P < 0.05) during ACE inhibitor treatment, and spleen tissue blood flow decreased significantly [from 2.54 ± 1.03 to 1.31 ± 0.61 ml/(min ± g)]. Normocapnic hypoxemia (Po2 42 ± 6 torr; oxyhemoglobin saturation 50.7 ± 18.0%) for 30 min during ACE inhibition was associated with increased (P < 0.01) heart [from 2.72 ± 1.52 to 8.87 ± 5.78 ml/(min ± g)] and adrenal [from 2.75 ± 1.88 to 6.43 ± 2.82 ml/(min ± g)] tissue blood flow, decreased (P < 0.01) spleen [from 1.31 ± 0.60 to 0.48 ± 0.57 ml/(min·g)] tissue blood flow, and unchanged (P > 0.05) blood flow to jejunum [from 2.51 ± 0.67 to 2.63 ± 2.00 ml/(min ± g)], ileum [from 0.82 ± 0.28 to 0.84 ± 0.42 ml/(min ± g)], liver [from 0.19 ± 0.13 to 0.43 ± 0.41 ml/(min ± g)] and skeletal muscle [from 0.11 ± 0.09 to 0.48 ± 0.57 ml/(min ± g)] tissues. Responses to hypoxemia were similar in control lambs, except that comparisons of the change (Δ) in tissue blood flow in response to hypoxemia in control versus captopril-treated lambs for ileum [Δileum −0.32 ± 0.29 versus 0.03 ± 0.40 ml/(min ± g)] and jejunum [Δjejunum −1.60 ± 2.20 versus 0.60 ± 2.00 ml/(min ± g)] demonstrated a greater fall in blood flow to these tissues in response to hypoxemia in control lambs. Thus, the products of ACE may be important in maintenance of baseline arterial pressure in the maturing animal. Furthermore, these products may be important in splanchnic vasoconstrictive responses to stress such as hypoxemia in the maturing animal.