Organ Tissue Blood Flow Responses to Hypoxemia in Lambs: Effect of Angiotensin Converting Enzyme Inhibitor

Abstract

SummaryChronically-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 12.5 pg/(kg*min)], which significantly ( P < 0.01) decreased arterial concentrations (mean + S.D.) of angiotensin-I1 (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 pg/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 (Poz 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)l tissue blood flow, decreased (P < 0.01) spleen [from 1. 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. Abbreviations AI, angiotensin I AII, angiotensin I1 ACE, angiotensin converting enzyme Aldo, aldosterone HR, heart rate MAP, mean arterial pressure RAA, renin-angiotensin-aldosterone Activity of the renin-angiotensin-aldosterone (RAA) system is increased in newborns in comparison to adults (12, 15, 18-20, 24, 25), and decreases rapidly with increasing postnatal age (6,10,23,25,27,29). Responsiveness of this system may also vary with postnatal age (29). The contribution of this system to the control of organ tissue blood flow in newborn animals is unknown. Furthermore, its importance in pathophysiologic conditions, such as hypoxemia, during maturation is not clear. Activity of RAA system is increased in response to hypoxemia (1,14,22,30,32) and is accompanied by a redistribution of organ tissue arterial blood flow (...

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

“…In normal lambs, converting enzyme inhibition lowers aortic pressure without changing organ blood flow. 29 In control lambs in this study, captopril lowered mean right and left atrial pressures, but the change in R, was not significant.…”

Chronic Hypoxemia in the Newborn Lamb: Cardiovascular, Hematopoietic, and Growth Adaptations

“…Several authors have studied acute hypoxemia in the developing organism and elucidated its effects on general cardiovascular function (1)(2)(3), regional blood flow (1,4,5), metabolic activity (6,7), and course of decompensation (1). The effects of sympathetic blockade (8,9) and decreasing Hb oxygen affinity (10,11) on the response to acute hypoxemia have also been addressed.…”

Control of aldosterone secretion in domestic mammals during the perinatal period

“…-Intravenous injection (Fleischman et al, 1975) or infusion Fisher, 1977, 1980) (Siegel, 1981 b). Inhibition of the angiotensin-converting enzyme with captopril in chronically catheterized 2 to 38-day old lambs was associated with a decrease in plasma angiotensin II and aldosterone concentrations (Weismann et al, 1983) (Siegel, 1979 In the newborn lamb and calf, the RAS is functional and responds to stimulation. Renin release by the newborn kidney can be suppressed by angiotensin II in the lamb, and the negative feedback inhibition of angiotensin 11 on renin release is similar throughout the first month of postnatal life while aldosterone response to angiotensin II is age-dependent.…”