Plasma angiotensin II levels in hypoxic and hypovolemic stress in unanesthetized rabbits

Zakheim, Richard M.; Molteni, Agostino; Mattioli, Leone; Park, M.

doi:10.1152/jappl.1976.41.4.462

Cited by 47 publications

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“…The increased cardiac output, however, presumably augments nutrient and 02 delivery to peripheral tissues, and hence may be beneficial. We and others (21,22) have also found a prompt decline in arterial AII concentrations in acutely hypoxic animals. These declines are associated with decreased systemic vascular resistance, having the effect ofreducing left ventricular afterload.…”

Section: Resultssupporting

confidence: 72%

Impaired Angiotensin Conversion and Bradykinin Clearance in Experimental Canine Pulmonary Emphysema

Stalcup¹,

Leuenberger²,

Lipset³

et al. 1981

J. Clin. Invest.

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A B S T R A C T Chronic hypoxic lung diseases are associated with abnormal blood pressure regulation. Because the lung is the principal site of angiotensin conversion and because hypoxia decreases converting enzyme activity, we examined whether angiotensin converting enzyme activity was impaired in lung disease. 12 dogs received a 6 wk course of aerosolized and intratracheal papain that produced moderate panlobular emphysema. These dogs and 24 control dogs were anesthetized and sampling catheters were placed under fluoroscopic control. Angiotensin conversion was measured by a blood pressure response bioassay. Pulmonary converting enzyme activity was also assessed by infusing bradykinin (BK) and using radioimmunoassay to measure the instantaneous clearance of BK and the concentration of BK in the pulmonary artery which first produced spillover of BK into left atrial blood. Angiotensin conversion was reduced in the emphysematous dogs to 81.1% (13.2 SD) from 92% (6 SD) in the control dogs (P < 0.01). Instantaneous clearance of BK in the emphysematous dogs was only slightly reduced (93%), despite reduction in their Pao2 to 75 mm Hg, indicating that the greatest proportion of the perfused vascular bed was exposed to alveolar Po2 of >90 mm Hg. However, the barrier to BK passage provided by the lung, and measured by the spillover level, was reduced Y4 to ½2 that observed in control animals. That the defect was promptly corrected by supplemental oxygen indicates that regional pulmonary vascular converting enzyme activity had been impaired by regional alveolar hypoxia, which permitted some peptide to pass through the lungs (2). In men with lung disease sufficient to reduce arterial Po2 below 60 Torr, the same defects were observed and were reversed when supplemental oxygen was provided (3). Cohn and Luria (4) found that men with pulmonary emphysema failed to demonstrate increased systemic vascular resistance in response to shock, regardless of the precipitating event. Anderson et al. (5) found that the resting blood pressures of 30 men with mild to severe emphysema were significantly lower than controls. Other studies suggest that the defect is not exclusive for emphysema, but extends to other lung disease. In patients with cystic fibrosis, whether mild or severe, Lieberman and Rodbard (6) observed lower blood pressure; these patients also had a lower pressor response to exercise. The underlying mechanisms contributing to all ofthese conditions remain unknown, but they raise the possibility ofan interplay between disease ofthe lung parenchyma and control of systemic blood pressure in the whole organism.We have shown that acute hypoxia reduces the activity of angiotensin converting enzyme (7-9). pressor response to injected angiotensin I, as well as pulmonary bradykinin clearance, was reduced in hypoxic animals. We speculated that injury to the pulmonary vascular bed, occurring as a consequence ofthe development of pulmonary emphysema, could interfere with converting enzyme activity and blood pressure regulation in two ...

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Section: Resultssupporting

confidence: 72%

Impaired Angiotensin Conversion and Bradykinin Clearance in Experimental Canine Pulmonary Emphysema

Stalcup¹,

Leuenberger²,

Lipset³

et al. 1981

J. Clin. Invest.

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“…Fur- Table 1 Response to challenge with U-46619: Rise in mean pulmonary arterial pressure (PAP; mmHg) above baseline in response to U-46619 5 pg kg-' given as a bolus injection before and 5 min after intervention with saline or AT, receptor antagonist (Los, losartan; GR, GR138950C) thermore, there was a small increase in abundance of this receptor during the first week of exposure to hypoxia. This occurred in spite of evidence that circulating All levels increase during this time (Zakheim et al, 1976), a situation which might be expected to down-regulate All receptors. The increase in All binding sites does not appear to be part of a generalized cellular response to hypoxia; previous studies have reported no change in the density of vasointestinal polypeptide binding sites and the selective downregulation of the atrial natriuretic peptide clearance receptor in hypoxic rat lungs (Li et al, 1995;.…”

Section: Discussionmentioning

confidence: 80%

“…However, studies based on changes in All levels and angiotensin-converting enzyme (ACE) activity have failed to define its role. Circulating All levels have been reported to increase during the first week of exposure to hypoxia but thereafter decline to baseline (Zakheim et al, 1976). Several early studies indicated that whole lung ACE activity is reduced by chronic exposure to hypoxia (Keane et al, 1982;Kay et al, 1985;Jederlinic et al, 1988), but recently a local increase in ACE levels has been observed in the walls of newly muscularized pulmonary arteries in hypoxic rat lung (Morrell et al, 1995a).…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II receptor expression and inhibition in the chronically hypoxic rat lung

Zhao¹,

Al-Tubuly²,

Sebkhi³

et al. 1996

British J Pharmacology

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“…Several lines of evidence support this hypothesis. First, chronic hypoxia has been reported to increase the ANG II circulating levels (42). Second, ANG II has been reported in vitro to increase the levels of AT 2 receptors through translational and not through transcriptional mechanisms (17).…”

Section: Discussionmentioning

confidence: 99%

Cardiac modulations of ANG II receptor expression in rats with hypoxic pulmonary hypertension

Adamy

Oliviéro

Eddahibi

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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. Cardiac modulations of ANG II receptor expression in rats with hypoxic pulmonary hypertension. Am J Physiol Heart Circ Physiol 283: H733-H740, 2002. First published April 18, 2002 10.1152/ ajpheart.01088.2001.-Right ventricular myocardial hypertrophy during hypoxic pulmonary hypertension is associated with local renin-angiotensin system activation. The expression of angiotensin II type 1 (AT 1) and type 2 (AT2) receptors in this setting has never been investigated. We have therefore examined the chronic hypoxia pattern of AT 1 and AT2 expression in the right and left cardiac ventricles, using in situ binding and RT-PCR assays. Hypoxia produced right, but not left, ventricular hypertrophy after 7, 14, and 21 days, respectively. Hypoxia for 2 days was associated in each ventricle with a simultaneous and transient increase (P Ͻ 0.05) in AT1 binding and AT1 mRNA levels in the absence of any significant change in AT 2 expression level. Only after 14 days of hypoxia, AT 2 binding increased (P Ͻ 0.05) in the two ventricles, concomitantly with a right ventricular decrease (P Ͻ 0.05) in AT 2 mRNA. Along these data, AT1 and AT2 binding remained unchanged in both the left and hypertrophied right ventricles from rats treated with monocrotaline for 30 days. These results indicate that chronic hypoxia induces modulations of AT1 and AT2 receptors in both cardiac ventricles probably through direct and indirect mechanisms, respectively, which modulations may participate in myogenic (at the level of smooth or striated myocytes) rather than in the growth response of the heart to hypoxia. chronic hypoxia; heart ventricles; angiotensin II; AT1 and AT 2 receptor subtypes CHRONIC HYPOXIA-INDUCED pulmonary hypertension is characterized by an increased pulmonary vascular resistance due to pulmonary artery thickening that impedes ejection of blood by the cardiac right ventricle (RV) and leads to RV hypertrophy (1,20,21,33). Evidence that chronic hypoxia increases the plasma levels of renin (9), angiotensin-converting enzyme (ACE) (24), and angiotensin II (ANG II) (42) has stimulated interest in the contribution of the renin-angiotensin system to the hypoxia-induced cardiopulmonary changes. This hypothesis is supported by data from chronically hypoxic rats showing that ACE inhibitor treatment reduces pulmonary arterial pressure (5,14,26,27,34,41), pulmonary artery thickening (5, 26, 27, 41), and RV hypertrophy (14,26,32,41).Two pharmacologically distinct subtypes of receptors, designated as AT 1 and AT 2 , participate in regulating ANG II activity. Both have been described based on their affinity for selective receptor antagonists and their sensitivity to reducing agents (6). Whereas AT 1 mediates the vasoconstrictor and growth-promoting effects of ANG II, AT 2 has been suggested to mediate vasodilator effects and to exert antigrowth action within many cell types, including vascular smooth muscle cells, endothelial cells, cardiac fibroblasts, and myocytes (6,12,22,23). We have shown in the rat hypoxic lung that AT 1 and AT 2 receptor e...

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Plasma angiotensin II levels in hypoxic and hypovolemic stress in unanesthetized rabbits

Cited by 47 publications

References 0 publications

Impaired Angiotensin Conversion and Bradykinin Clearance in Experimental Canine Pulmonary Emphysema

Impaired Angiotensin Conversion and Bradykinin Clearance in Experimental Canine Pulmonary Emphysema

Angiotensin II receptor expression and inhibition in the chronically hypoxic rat lung

Cardiac modulations of ANG II receptor expression in rats with hypoxic pulmonary hypertension

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