Inhibition of converting enzyme activity by acute hypoxia in dogs

Stalcup, S. Alex; Lipset, J. S.; Legant, P. M.; Leuenberger, P.; Mellins, Robert B.

doi:10.1152/jappl.1979.46.2.227

Cited by 65 publications

(30 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Using a blood pressure response bioassay in intact, anesthetized dogs, we demonstrated that acute alveolar hypoxia impaired AI conversion (9). Subsequently, we have confirmed this finding using radioimmunoassay of extracted BK to assess converting enzyme activity across the pulmonary and systemic vascular beds ofdogs (10). To characterize the cellular basis for the inhibition of converting enzyme activity by hypoxia, we have developed an in vitro system using cultured endothelial cells.…”

Section: Abstract Endothelial Cells In Tissue Culturementioning

confidence: 75%

Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia.

Stalcup¹,

Lipset²,

Woan³

et al. 1979

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T Endothelial cells in tissue culturedegrade bradykinin and convert angiotensin I to angiotensin II. These are both functions of a single dipeptidyl hydrolase, angiotensin converting enzyme. Monolayer cultures were prepared from human, rabbit, pig, and calf vessels. Angiotensin converting enzyme activity was assessed by adding either bradykinin or angiotensin I to the cells in culture flasks, and measuring residual peptide over time by radioimmunoassay. Peptide degradation was inhibited by the specific converting enzyme inhibitor, SQ 20881. The flasks were equilibrated with varying hypoxic gas mixtures: hypoxia rapidly (<2 min) decreased enzyme activity and room air restored it as rapidly. The extent to which activity was reduced was a direct function of Po2 (r = 0.93, P < 0.001), and there was no enzyme activity below a Po2 of 30 mm Hg. Four preparations were studied with respect to decrease in enzyme activity by hypoxia: (a) intact cells in monolayer, (b) sonicated cells, (c) sonicated cells from which converting enzyme was partially dissolved by a detergent, and (d) purified converting enzyme. Hypoxia had progressively less of an inhibiting effect on the enzyme activity of the preparations as the degree of cell integrity decreased. Hypoxia inhibits angiotensin converting enzyme activity in cultured endothelial cells, but the effect of hypoxia is not on the enzyme per se, but appears to be a unique characteristic of the endothelial cell.

show abstract

Section: Abstract Endothelial Cells In Tissue Culturementioning

confidence: 75%

Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia.

Stalcup¹,

Lipset²,

Woan³

et al. 1979

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Because of the apparent role of thyroid hormones in lung maturation (7), cord blood content of iodothyronines and TSH has been extensively evaluated with interest. Several investigators have found reduced thyroid hormone concentration in cord blood of such babies (4,5,14). Thus, they have suggested a thyroid role in the pathogenesis of IRDS.…”

Section: Discussionmentioning

confidence: 99%

“…We interpreted these results as showing that tonic activity of the renin-angiotensin system normally damps fluctuations in peripheral vasomotor tone and that blockade permits maximal fluctuations in blood pressure which are then translated into heart rate fluctuations through the mediation of the autonomic nervous system. It has been documented in a canine model that acute hypoxia (14) of even a mild degree can signifi- cantly inhibit angiotensin-converting enzyme. In preliminary experiments, we have found in chronically instrumented newborn lambs that 17% Oz breathing enhances by approximately 90% the power in low frequency HR fluctuations.…”

Section: Sudden Infant Death Syndrome 925mentioning

confidence: 99%

Sudden Infant Death Syndrome: Abnormalities in Short Term Fluctuations in Heart Rate and Respiratory Activity

et al. 1984

View full text Add to dashboard Cite

SummaryIn order to test the hypothesis that a defect in cardiorespiratory regulation contributes to death of infants from sudden infant death syndrome (SIDS), we analyzed the power spectra of heart rate and respiratory activity during 256-sec epochs of quiet sleep. Data were obtained from pneumogram recordings performed for 12 h at night on eight infants who subsequently died from SIDS and 22 age-matched control infants. We computed the heart rate and respiratory power spectra from a single epoch on each infant using an algorithm developed for an 8085 microprocessor system dedicated to this investieation. There was no statistically sienificant difference betweenvSID~ and controls based on mean-respiratory and heart rates. Spectral analysis revealed enhancement in general has rested on the analysis of naturally occurring fluctuations in system variables (4). These fluctuations contain information concerning the spontaneously changing load on the system as well as the system's response. A useful first step in the quantitative analysis of the control system is the spectral analysis of the system variables. Prior work (1, 7, 9, 11) has emphasized the importance and relevance of the analysis of fluctuations in heart rate to assess autonomic functions. We present here the results of spectral analysis of 256-sec-long segments ofthe instantaneous heart and respiratory waveform in 22 control infants and eight infants who died of SIDS. MATERIALS AND METHODSof low frequency power in the 0.02 to 0.1 Hz band in the heart rate power spectrum in the SIDS group compared to control ( p Infants who died of SIDS diagnosed after an autopsy failed to < 0.002) and dispersion in respiratory frequency as determined identify the cause of death were evaluated because they all had by the respiratory band width ( p < 0.0000~). These data suggest at least one nocturnal recording of ECG and respiration at home. that a predisposition to SIDS manifests itself in an abnormal The indications for conducting the recording were near-SIDS pattern of fluctuations in heart rate and respiratory activity.(2), choking spells (2), and death from SIDS in one sibling (1) or two siblinns (2). One of the latter also exmrienced a near--. , SIDS event. Thus, three had not experiencedmnear-SIDS; in two Abbreviations of these, GER was identified on barium swallow. Although she SIDS, sudden infant death syndrome had no choking spells, GER was also identified in a sibling with ECG, electrocardiogram near-SIDS (patient 7, Table 1). The shortest interval between a EEG, electroencephalogram spell and the nocturnal recording was 5 days (the first recording GER, gastroesophageal reflux in patient 7). Near-SIDS was defined as sleep onset apnea asso-HR, heart rate ciated with limpness and cyanosis or pallor responding only to vigorous stimulation or resuscitation. Identifiable causes of pathologic apnea were ruled out by complete blood count, ECG, The purpose of this investigation was to test the hypothesis EEG, chest x-ray, serum Na' , K' , C1-, HC03-, and Ca2+, and sugg...

show abstract

“…The animals were then abruptly switched to the hypoxic gas mixture (10% 02, 90% N2) for a 60-min interval. This gas mixture was chosen to achieve a Pao2 between 30-40 mm Hg; in this range, angiotensin-converting enzyme activity is markedly inhibited (2). Because inhibition of enzyme activity is rapidly reversible, we then abruptly switched the gas back to room air, and continued observations for 60 min after reoxygenation.…”

Section: Methodsmentioning

confidence: 99%

“…Previous work from our laboratory has demonstrated that ACE activity is rapidly and reversibly inhibited by hypoxia in vivo (2,3) and in endothelial cell culture in vitro (4). In previous publications, we suggested that this phenomenon contributed to: (a) abnormal circulatory responses to stress in a canine model of pulmonary emphysema (5), (b) the physiologic adaptations of the circulation at the time of birth (6), and (c) the edema-producing effect of bradykinin in the hypoxic pulmonary vascular bed (7,8).…”

Section: Introductionmentioning

confidence: 94%

Systemic circulatory adjustments to acute hypoxia and reoxygenation in unanesthetized sheep. Role of renin, angiotensin II, and catecholamine interactions.

Davidson¹,

Stalcup²

1984

J. Clin. Invest.

View full text Add to dashboard Cite

Abstract. The hemodynamic consequences of the hypoxic inhibition of angiotensin-converting enzyme activity were studied in chronically instrumented unanesthetized sheep (n = 8) breathing a hypoxic gas mixture for 60 min (Pao2 = 31 mm Hg) followed by reoxygenation with room air. Changes in cardiac output, vascular pressures, blood flow distribution, arterial pH, Paco2, Pao2, and arterial levels of plasma renin activity, angiotensin II, bradykinin, and catecholamines were measured at selected time points. Seven additional sheep underwent the same protocol but received saralasin, an angiotensin II receptor blocker beginning at 55 min of hypoxia and extending into the reoxygenation period. During hypoxia, both groups developed identical hemodynamic patterns including a rise in cardiac output (25%), blood pressure (15%), and preferential blood flow distribution to the heart, brain, adrenals, diaphragm, and skeletal muscle, as well as a decrease in the fraction of cardiac output to the kidneys and most ofthe gut. This was associated with a decrease in angiotensin II concentrations (from 35 to 17 pg/ml) in spite of a doubling in plasma renin activity and catecholamines. Bradykinin levels did not change. Upon reoxygenation, bolus production of angiotensin II (from 17 to 1,819 pg/ml) occurred in spite of a constant level of plasma renin activity. Concurrently, different he-

show abstract

Inhibition of converting enzyme activity by acute hypoxia in dogs

Cited by 65 publications

References 0 publications

Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia.

Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia.

Sudden Infant Death Syndrome: Abnormalities in Short Term Fluctuations in Heart Rate and Respiratory Activity

Systemic circulatory adjustments to acute hypoxia and reoxygenation in unanesthetized sheep. Role of renin, angiotensin II, and catecholamine interactions.

Contact Info

Product

Resources

About