angiotensin-i and Hypoxia

Alternative branches of the classical renin-angiotensin-aldosterone system (RAS) represent an important cascade in which angiotensin 2 (AngII) undergoes cleavage via the action of the angiotensin-converting enzyme 2 (ACE2) with subsequent production of Ang(1-7) and other related metabolites eliciting its effects via Mas receptor activation. Generally, this branch of the RAS system is described as its non-canonical alternative arm with counterbalancing actions to the classical RAS, conveying vasodilation, anti-inflammatory, anti-remodeling and anti-proliferative effects. The implication of this branch was proposed for many different diseases, ranging from acute cardiovascular conditions, through chronic respiratory diseases to cancer, nonetheless, hypoxia is one of the most prominent common factors discussed in conjugation with the changes in the activity of alternative RAS branches. The aim of this review is to bring complex insights into the mechanisms behind the various forms of hypoxic insults on the activity of alternative RAS branches based on the different duration of stimuli and causes (acute vs. intermittent vs. chronic), localization and tissue (heart vs. vessels vs. lungs) and clinical relevance of studied phenomenon (experimental vs. clinical condition). Moreover, we provide novel insights into the future strategies utilizing the alternative RAS as a diagnostic tool as well as a promising pharmacological target in serious hypoxia-associated cardiovascular and cardiopulmonary diseases.

Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Animals; COVID-19; Humans; Hypoxia; Lung; Myocardial Infarction; Peptide Fragments; Renin-Angiotensin System; SARS-CoV-2

Topics: Angiotensin I; Angiotensin II; Animals; Blood Flow Velocity; Cardiomegaly; Coronary Vessels; Dogs; Humans; Hypoxia; In Vitro Techniques; Myocardial Ischemia; Peptidyl-Dipeptidase A; Rats; Renin-Angiotensin System; Swine

Topics: Angiotensin I; Animals; Bradykinin; Humans; Hypoxia; In Vitro Techniques; Kinetics; Lung; Oligopeptides; Peptides; Peptidyl-Dipeptidase A; Teprotide

Tsantan Sumtang, which consists of Choerospondias axillaris (Roxb.) Burtt et Hill, Myristica fragrans Houtt and Santalum album L, is a traditional and common prescription of Tibetan medicine. Tsantan Sumtang originates from Four Tantra with properties of nourishing heart and has been used as a folk medicine for cardiovascular diseases and heart failure in Qinghai, Tibet and Inner Mongolia. Our previous studies found that Tsantan Sumtang showed beneficial effects on right ventricular structure in hypoxia rats, while the underling mechanism remains unclear.. To elucidate the underlying mechanisms of Tsantan Sumtang attenuated right ventricular (RV) remodeling and fibrosis of chronic hypoxia-induced pulmonary arterial hypertension (HPAH) rats.. Our results showed that RVHI, RV/TL and RVSP were significantly increased in HPAH rat. Furthermore, levels of collagen I, collagen III and hydroxyproline were up-regulated in RV tissue under hypoxia. We found that RV hypertrophy and fibrosis were associated with increased expression of ACE, AngII, AT1R as well as decreased expression of ACE2, Ang1-7 and Mas. RV remodeling and fibrosis were attenuated after Tsantan Sumtang administration by up-regulating ACE2 and Mas level as well as down-regulating ACE, AngII and AT1R levels in RV tissue. 35 constituents in Tsantan Sumtang were identified.. Tsantan Sumtang attenuated RV remodeling and fibrosis in rat exposed to chronic hypoxia. The pharmacological effect of Tsantan Sumtang was based on equilibrating ACE-AngII-AT1R and ACE2-Ang1-7-Mas axis of RV tissue in HPAH rat.

Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Fibrosis; Hypertrophy, Right Ventricular; Hypoxia; Male; Medicine, Tibetan Traditional; Peptide Fragments; Peptidyl-Dipeptidase A; Plant Preparations; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Ventricular Remodeling

Topics: Angiotensin I; Angiotensin-Converting Enzyme 2; Gastrointestinal Microbiome; Humans; Hypertension, Pulmonary; Hypoxia; Lung

The aim of this study was to investigate the mechanism of fasudil alleviating hypoxic pulmonary hypertension (HPH).. A total of 50 Sprague-Dawley rats were randomized into control, model and fasudil intervention groups. Hemodynamic and pulmonary pathomorphology data were collected using Powerlab system and hematoxylin and eosin staining. The protein expression of Ang-(1-7) was detected by immunohistochemical staining and ELISA assay in vivo or in vitro. Western blot was utilized to observe the protein expression of ACE2 and HIF-1α in vitro.. Fasudil treatment repressed the elevation of RVSP, RV/(LV+S), attenuated the pulmonary vascular structure remodeling (PVSR) of pulmonary arterioles induced by chronic hypoxia, and stabilized the expression of Ang-(1-7) in vivo and in vitro. In addition, experiments consistently indicated an escalation of ACE2 and a reduction of HIF-1α.. Our results suggest that fasudil can effectively attenuate PVSR and PH. The underlying mechanism may partially up-regulated Ang-(1-7) and ACE2, and lessened HIF-1α.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Angiotensin I; Animals; Gene Expression; Hypertension, Pulmonary; Hypoxia; Peptide Fragments; Rats; Rats, Sprague-Dawley; Signal Transduction

Obstructive sleep apnea is associated with inflammation and oxidative stress in lung tissues and can lead to metabolic abnormalities. We investigated the effects of angiotensin1-7 [Ang-(1-7)] on lung injury in rats induced by chronic intermittent hypoxia (CIH). We randomly assigned 32 male Sprague-Dawley rats (180-200 g) to normoxia control (NC), CIH-untreated (uCIH), Ang-(1-7)-treated normoxia control (N-A), and Ang-(1-7)-treated CIH (CIH-A) groups. Oxidative stress biomarkers were measured in lung tissues, and expression of NADPH oxidase 4 (Nox4) and Nox subunits (p22phox, and p47phox) was determined by Western blot and reverse transcription-polymerase chain reaction. Pulmonary pathological changes were more evident in the uCIH group than in the other groups. Enzyme-linked immunosorbent assays and immunohistochemical staining showed that inflammatory factor concentrations in serum and lung tissues in the uCIH group were significantly higher than those in the NC and N-A groups. Expression of inflammatory factors was significantly higher in the CIH-A group than in the NC and N-A groups, but was lower than in the uCIH group (P<0.01). Oxidative stress was markedly higher in the uCIH group than in the NC and N-A groups. Expression of Nox4 and its subunits was also increased in the uCIH group. These changes were attenuated upon Ang-(1-7) treatment. In summary, treatment with Ang-(1-7) reversed signs of CIH-induced lung injury via inhibition of inflammation and oxidative stress.

Topics: Angiotensin I; Animals; Blotting, Western; Cytokines; Enzyme-Linked Immunosorbent Assay; Hypoxia; Immunohistochemistry; Inflammation; Lung; Lung Injury; Male; Malondialdehyde; Oxidative Stress; Peptide Fragments; Protective Agents; Random Allocation; Rats, Sprague-Dawley; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Sleep Apnea, Obstructive; Vasodilator Agents

The aim of the present study was to test the hypothesis that chronic hypoxia would aggravate hypertension in Ren-2 transgenic rats (TGR), a well-defined monogenetic model of hypertension with increased activity of endogenous renin-angiotensin system (RAS). Systolic blood pressure (SBP) in conscious rats and mean arterial pressure (MAP) in anesthetized TGR and normotensive Hannover Sprague-Dawley (HanSD) rats were determined under normoxia that was either continuous or interrupted by two weeks´ hypoxia. Expression, activities and concentrations of individual components of RAS were studied in plasma and kidney of TGR and HanSD rats under normoxic conditions and after exposure to chronic hypoxia. In HanSD rats two weeks´ exposure to chronic hypoxia did not alter SBP and MAP. Surprisingly, in TGR it decreased markedly SBP and MAP; this was associated with substantial reduction in plasma and kidney renin activities and also of angiotensin II (ANG II) levels, without altering angiotensin-converting enzyme (ACE) activities. Simultaneously, in TGR the exposure to hypoxia increased kidney ACE type 2 (ACE2) activity and angiotensin 1-7 (ANG 1-7) concentrations as compared with TGR under continuous normoxia. Based on these results, we propose that suppression of the hypertensiogenic ACE-ANG II axis in the circulation and kidney tissue, combined with augmentation of the intrarenal vasodilator ACE2-ANG 1-7 axis, is the main mechanism responsible for the blood pressure-lowering effects of chronic hypoxia in TGR.

Topics: Age Factors; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Animals; Blood Pressure; Disease Models, Animal; Hypertension; Hypoxia; Kidney; Peptide Fragments; Peptidyl-Dipeptidase A; Proto-Oncogene Mas; Proto-Oncogene Proteins; Rats, Sprague-Dawley; Rats, Transgenic; Receptors, G-Protein-Coupled; Renin; Renin-Angiotensin System; Signal Transduction; Vasoconstriction; Vasodilation

The present study was performed to evaluate the role of intrapulmonary activity of the two axes of the renin-angiotensin system (RAS): vasoconstrictor angiotensin-converting enzyme (ACE)/angiotensin II (ANG II)/ANG II type 1 receptor (AT₁) axis, and vasodilator ACE type 2 (ACE2)/angiotensin 1-7 (ANG 1-7)/Mas receptor axis, in the development of hypoxic pulmonary hypertension in Ren-2 transgenic rats (TGR). Transgene-negative Hannover Sprague-Dawley (HanSD) rats served as controls. Both TGR and HanSD rats responded to two weeks´ exposure to hypoxia with a significant increase in mean pulmonary arterial pressure (MPAP), however, the increase was much less pronounced in the former. The attenuation of hypoxic pulmonary hypertension in TGR as compared to HanSD rats was associated with inhibition of ACE gene expression and activity, inhibition of AT₁receptor gene expression and suppression of ANG II levels in lung tissue. Simultaneously, there was an increase in lung ACE2 gene expression and activity and, in particular, ANG 1-7 concentrations and Mas receptor gene expression. We propose that a combination of suppression of ACE/ANG II/AT₁receptor axis and activation of ACE2/ANG 1-7/Mas receptor axis of the RAS in the lung tissue is the main mechanism explaining attenuation of hypoxic pulmonary hypertension in TGR as compared with HanSD rats.

Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Animals; Arterial Pressure; Disease Models, Animal; Hypertension, Pulmonary; Hypoxia; Lung; Peptide Fragments; Peptidyl-Dipeptidase A; Proto-Oncogene Mas; Proto-Oncogene Proteins; Rats, Sprague-Dawley; Rats, Transgenic; Receptor, Angiotensin, Type 1; Receptors, G-Protein-Coupled; Renin; Renin-Angiotensin System; Signal Transduction; Vasoconstriction; Vasodilation

We previously demonstrated that mice which overexpress human renin and angiotensinogen (R+A+) show enhanced cerebral damage in both in vivo and in vitro experimental ischemia models. Angiotensin-converting enzyme 2 (ACE2) counteracts the effects of angiotensin (Ang-II) by transforming it into Ang-(1-7), thus reducing the ligand for the AT1 receptor and increasing stimulation of the Mas receptor. Triple transgenic mice, SARA, which specifically overexpress ACE2 in neurons of R+A+ mice were used to study the role of ACE2 in ischemic stroke using oxygen and glucose deprivation (OGD) of brain slices as an in vitro model. We examined tissue swelling, the production of reactive oxygen species (ROS), and cell death in the cerebral cortex (CX) and the hippocampal CA1 region during OGD. Expression levels of NADPH oxidase (Nox) isoforms, Nox2 and Nox4 were measured using western blots. Results show that SARA mice and R+A+ mice treated with the Mas receptor agonist Ang-(1-7) had less swelling, cell death, and ROS production in CX and CA1 areas compared to those in R+A+ animals. Treatment of slices from SARA mice with the Mas antagonist A779 eliminated this protection. Finally, western blots revealed less Nox2 and Nox4 expression in SARA mice compared with R+A+ mice both before and after OGD. We suggest that reduced brain swelling and cell death observed in SARA animals exposed to OGD result from diminished ROS production coupled with lower expression of Nox isoforms. Thus, the ACE2/Ang-(1-7)/Mas receptor pathway plays a protective role in brain ischemic damage by counteracting the detrimental effects of Ang-II-induced ROS production.

Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Animals; Brain; Brain Edema; Brain Ischemia; CA1 Region, Hippocampal; Cell Death; Cerebral Cortex; Glucose; Hypoxia; Membrane Glycoproteins; Mice, Transgenic; NADPH Oxidase 2; NADPH Oxidase 4; NADPH Oxidases; Neurons; Peptide Fragments; Peptidyl-Dipeptidase A; Proto-Oncogene Mas; Proto-Oncogene Proteins; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Receptors, G-Protein-Coupled; Signal Transduction; Stroke; Tissue Culture Techniques

To investigate the effect of angiotensin-(1-7) [Ang(1-7)] on the transdifferentiation of normal rat kidney proximal tubular epithelia cells (NRK52E) under hypoxic condition induced by cobaltous chloride (Co) and the underlying mechanism.. NRK52E cells were divided into control group, Co group, Co+Ang-(1-7) group and Ang-(1-7) group and cultured for 6 d. Expression levels of hypoxia-inducible factor-1α (HIF-lα) and α-smooth muscle actin (α-SMA) were detected by immunocytochemistry. Immunohistochemistry and Western blotting were used to determine the expression of p-ERK1/2 and ELISA to measure the content of collagen type 1 (Col I) in the culture supernatant.. Compared with the control group, the expressions of HIF-lα, α-SMA, Col Iand p-ERK1/2 in the Co group and the Co+Ang-(1-7) group increased significantly (P<0.05) 6 d later. Compared with the Co group, the expressions of HIF-lα, α-SMA, Col Iand p-ERK1/2 in the Co+Ang-(1-7) group decreased significantly (P<0.05).. Ang-(1-7) can inhibit Co-induced rats' tubular epithelial-to-mesenchymal transition and reduce the production of extracellular matrix. Inhibition of ERK1/2 pathway may play an important role in this process.

Topics: Actins; Angiotensin I; Animals; Cell Line; Cobalt; Collagen Type I; Epithelial-Mesenchymal Transition; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Kidney Tubules, Proximal; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Peptide Fragments; Rats

The present study attempted to evaluate the effects of chronic intermittent hypoxia (CIH) associated with sleep restriction in hemodynamic parameters and the plasma renin-angiotensin system. Wistar-Hannover rats were submitted to isolated CIH exposure (1000-1600 h), sleep restriction (1600-1000 h), defined as 18-h paradoxical sleep deprivation followed by 6-h sleep permission period and CIH associated to sleep restriction for 21 days. The CIH and sleep restriction group showed a preferential increase in renal sympathetic nervous system (rSNA) associated with a reduction in plasma angiotensin (1-7) concentrations. However, CIH-sleep restriction rats did not modify rSNA and showed a higher angiotensin (1-7) concentration when compared to isolated CIH and sleep restriction. These results suggest that CIH and sleep restriction impaired the cardiovascular system, and its association to sleep loss can modify these effects by partially restoring circulating angiotensin (1-7).

Topics: Angiotensin I; Animals; Chromatography, High Pressure Liquid; Disease Models, Animal; Electrophysiology; Hemodynamics; Hypertension; Hypoxia; Male; Peptide Fragments; Rats; Rats, Wistar; Renin-Angiotensin System; Sleep Apnea Syndromes; Sleep Deprivation; Sympathetic Nervous System

Reduced alveolar Po(2) in rats produces a rapid systemic inflammation characterized by reactive O(2) species generation, mast cell (MC) degranulation, leukocyte-endothelial interactions, and increased vascular permeability. The inflammation is not initiated by the low systemic Po(2) but rather by the release of monocyte chemoattractant protein-1 (MCP-1) from alveolar macrophages (AMO) activated by alveolar hypoxia. Circulating AMO-borne MCP-1 induces MC degranulation, which activates the local renin-angiotensin system (RAS) and mediates the microvascular inflammation. This study was directed to determine the mechanism of RAS activation by MCP-1-induced MC degranulation. Experiments in isolated rat peritoneal MCs showed the following: 1) Western blots and immunocytochemistry demonstrated the presence of renin and angiotensin-converting enzyme (ACE) in MCs and their release upon degranulation; 2) MCP-1-induced degranulation of MCs incubated in plasma produced an increase in angiotensin II (ANG II) concentration; and 3) this increase was inhibited completely by the following agents: the MCP-1 receptor antagonist RS-102895, the specific rat renin inhibitor WFML, or the ACE inhibitor captopril administered separately. Captopril also inhibited ANG II generation by MCs incubated in culture medium plus ANG I. The results show that peritoneal MCs contain active renin, which activates the RAS upon degranulation, and that peritoneal MCs are a source of ACE and suggest that conversion of ANG I to ANG II is mediated predominantly by ACE. This study provides novel evidence of the presence of active renin in rat peritoneal MCs and helps explain the mechanism of activation of the RAS during alveolar hypoxia.

Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Blotting, Western; Cell Degranulation; Cells, Cultured; Chemokine CCL2; Hypoxia; Immunohistochemistry; Inflammation; Macrophage Activation; Macrophages, Peritoneal; Peptidyl-Dipeptidase A; Pulmonary Alveoli; Rats; Rats, Sprague-Dawley; Receptors, CCR2; Renin; Renin-Angiotensin System

To determine whether the somatostatin receptor 2 (sst(2)) influences angiogenesis and its associated factors in a model of hypoxia-induced retinal neovascularization.. sst(1)-knockout (KO) mice, in which sst(2) is overexpressed and overfunctional, and sst(2)-KO mice were used. Angiogenesis was evaluated in fluorescein-perfused retinas. Angiogenesis-associated factors were determined by RT-PCR and immunohistochemistry.. Retinal neovascularization was increased in sst(2)-KO mice, but remained unchanged in sst(1)-KO compared with wild-type (WT) mice. Retinal levels of sst(2) mRNA were not affected by hypoxia. Normoxic levels of angiogenesis regulators were similar in WT and KO retinas except for mRNA levels of IGF-1, Ang-2, and its receptor Tie-2. In WT, hypoxia induced an increase in mRNA levels of (1) VEGF and its receptors, (2) IGF-1R, and (3) Ang-2 and Tie-2. The increase in VEGF and IGF-1R mRNAs was more pronounced after sst(2) loss, but was less pronounced when sst(2) was overexpressed. In addition, in hypoxic retinas, sst(2) loss increased IGF-1 mRNA, whereas it decreased Ang-1, Tie-1, and Tie-2 mRNA levels. Moreover, Tie-1 mRNA increased when sst(2) was overexpressed. Immunohistochemistry confirmed the results in hypoxic retinas on increased expression of VEGF, IGF-1, and their receptors after sst(2) loss. It also allowed the localization of these factors to specific retinal cells. In this respect, VEGFR-2, IGF-1, and IGF-1R were localized to Müller cells.. These results suggest that sst(2) may be protective against angiogenesis. The immediate clinical importance lies in the establishment of a potential pharmacological target based on sst(2) pharmacology.

Topics: Angiotensin I; Angiotensin II; Animals; Capillaries; Disease Models, Animal; Hypoxia; Insulin-Like Growth Factor I; Mice; Mice, Inbred C57BL; Mice, Knockout; Neovascularization, Pathologic; Receptor, IGF Type 1; Receptor, TIE-1; Receptor, TIE-2; Receptors, Somatostatin; Retinal Diseases; RNA, Messenger; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2

Adenosine is an important paracrine hormone in the cardiovascular system. Adenosine flux across cardiomyocyte membranes occurs mainly via equilibrative nucleoside transporters (ENTs). The role of the ENTs in adenosine physiology is poorly understood, particularly in response to metabolic stress such as hypoxia. Therefore, we investigated the effects of chronic hypoxia on ENT1, the predominant ENT isoform in cardiomyocytes.. HL-1 cells (immortalized murine cardiomyocytes) were exposed to hypoxia (2% O2) for 0-20 h. Cell viability, lactate dehydrogenase (LDH) release, glucose uptake, GLUT1 and GLUT4 protein, adenosine uptake, PKC activity, translocation profiles of PKCdelta and, nitrobenzylthioinosine (NBTI) binding and mENT1 mRNA levels were measured. The role of PKC in regulating mENT1 was further investigated using phorbol ester (100 nM, 18 h) and a dominant negative PKC construct, pSVK3PKC1-401.. HL-1 cells have typical cardiomyocyte responses to hypoxia based on cell viability, LDH release, glucose uptake and GLUT protein levels. Hypoxia (8-20 h) down-regulates mENT1-dependent adenosine uptake, NBTI-binding and PKC but not PKCdelta in HL-1 cells. Abrogation of PKC activity using chronic phorbol ester or a dominant negative PKC mimicked the effect of hypoxia on adenosine uptake suggesting that PKC is involved in regulation of mENT1. Hypoxia (4 h) decreases mENT1 mRNA, which returns to basal levels by 20 h.. Chronic hypoxia down-regulates mENT1 activity possibly via PKC. Hypoxia and PKC also regulate mENT1 RNA levels. Cardiomyocytes may regulate mENT1 (via PKC) to modulate release and/or uptake of adenosine. However, the relationship between mENT1 mRNA levels, protein levels and functional transport is complex.

Topics: Angiotensin I; Animals; Cell Line; Enzyme Activation; Equilibrative Nucleoside Transporter 1; Hypoxia; Mice; Mice, Transgenic; Myocytes, Cardiac; Protein Kinase C

In pulmonary hypertension, changes in pulmonary vascular structure and function contribute to the elevation in pulmonary artery pressure. The time-courses for changes in function, unlike structure, are not well characterised. Medial hypertrophy and neomuscularisation and reactivity to vasoactive agents were examined in parallel in main and intralobar pulmonary arteries and salt-perfused lungs from rats exposed to hypoxia (10% O2) for 1 and 4 weeks (early and established pulmonary hypertension, respectively). After 1 week of hypoxia, in isolated main and intralobar arteries, contractions to 5-hydroxytryptamine and U46619 (thromboxane-mimetic) were increased whereas contractions to angiotensins I and II and relaxations to acetylcholine were reduced. These alterations varied quantitatively between main and intralobar arteries and, in many instances, regressed between 1 and 4 weeks. The alterations in reactivity did not necessarily link chronologically with alterations in structure. In perfused lungs, constrictor responses to acute alveolar hypoxia were unchanged after 1 week but were increased after 4 weeks, in conjunction with the neomuscularisation of distal alveolar arteries. The data suggest that in hypoxic pulmonary hypertension, the contribution of altered pulmonary vascular reactivity to the increase in pulmonary artery pressure may be particularly important in the early stages of the disease.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acetylcholine; Angiotensin I; Angiotensin II; Animals; Hemodynamics; Hypertension, Pulmonary; Hypoxia; In Vitro Techniques; Lung; Organ Size; Pulmonary Artery; Pulmonary Circulation; Rats; Rats, Wistar; Renin-Angiotensin System; Serotonin; Vasodilator Agents

This study investigated whether adenosine mediates the decrease in plasma renin activity (PRA) during acute hypoxia. Eight chronically tracheotomized, conscious beagle dogs were kept under standardized environmental conditions and received a low-sodium diet (0.5 mmol.kg body wt(-1).day(-1)). During the experiments, the dogs were breathing spontaneously via a ventilator circuit: first hour, normoxia (21% inspiratory concentration of O(2)); second and third hours, hypoxia (10% inspiratory concentration of O(2)). Each of the eight dogs was studied twice in randomized order in control and theophylline experiments. In theophylline experiments, theophylline, an A(1)-receptor antagonist, was infused intravenously during hypoxia (loading dose: 3 mg/kg within 30 min, maintenance: 0.5 mg. kg(-1). h(-1)). In theophylline experiments, PRA (5.9 +/- 0.8 ng ANG I. ml(-1). h(-1)) and ANG II plasma concentration (15.9 +/- 2.3 pg/ml) did not decrease during hypoxia, whereas plasma aldosterone concentration decreased from 277 +/- 63 to 132 +/- 23 pg/ml (P < 0.05). In control experiments, PRA decreased from 6.8 +/- 0.8 during normoxia to 3.0 +/- 0.5 ng ANG I. ml(-1). h(-1) during hypoxia, ANG II decreased from 13.3 +/- 1.9 to 7.3 +/- 1.9 pg/ml, and plasma aldosterone concentration decreased from 316 +/- 50 to 70 +/- 13 pg/ml (P < 0.05). Thus infusion of the adenosine receptor antagonist theophylline inhibited the suppression of the renin-angiotensin system during acute hypoxia. The decrease in aldosterone occurred independently and is apparently directly related to hypoxia. In conclusion, it is likely that adenosine mediates the decrease in PRA during acute hypoxia in conscious dogs.

Topics: Acute Disease; Adenosine; Aldosterone; Angiotensin I; Angiotensin II; Animals; Blood Pressure; Carbon Dioxide; Consciousness; Diet, Sodium-Restricted; Dogs; Female; Heart Rate; Hemodynamics; Hypoxia; Oxygen; Partial Pressure; Potassium; Purinergic P1 Receptor Antagonists; Renin; Renin-Angiotensin System; Theophylline

The aims of this study were to investigate whether angiotensin II and/or endothelin could contribute to the hypoxic contractile response of isolated rat pulmonary artery. Experiments were performed for 1 h on noradrenaline precontracted arterial rings in hypoxic conditions (95% N2 and 5% CO2). Nicardipine, lisinopril, losartan, phosphoramidon, FR139317 and bosentan were used to block Ca2+ channels, angiotensin I-converting enzyme, AT1 receptors, endothelin-converting enzyme, ETA receptors, and ETA/ETB receptors, respectively. The profile of the hypoxic contractile response was biphasic, displaying, after a short relaxation, a weak and transient contraction (from 2-4 min) and then, before complete relaxation, a slowly developed but sustained contraction (from 14-60 min). Endothelium removal abolished the transient contraction and reduced (-59%) the sustained contraction. Nicardipine did not modify the transient contraction, but concentration-dependently decreased (from -35% to -100%) the sustained contraction (P = 0.024). Lisinopril and losartan did not affect the response (P = 0.418 and P = 0.973, respectively). Bosentan did not modify the transient contraction, but concentration-dependently decreased (from -14% to -71%) the sustained contraction (P = 0.016), whereas phosphoramidon and FR139317 did not affect the response (P = 0.830 and P = 0.806, respectively).. In rat, (i) both phases of the hypoxic contractile response are endothelium-dependent and independent of angiotensin II; (ii) the transient contraction does not depend on endothelin; (iii) the sustained contraction, which involves calcium influx, appears partly dependent on mature endothelin released from storage granules by stimulating ETB receptors.

Topics: Angiotensin I; Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Azepines; Bosentan; Calcium; Calcium Channel Blockers; Endothelin Receptor Antagonists; Endothelins; Endothelium, Vascular; Extracellular Space; Glycopeptides; Hypoxia; In Vitro Techniques; Indoles; Lisinopril; Losartan; Male; Muscle Contraction; Muscle, Smooth, Vascular; Nicardipine; Pulmonary Artery; Rats; Rats, Wistar; Sulfonamides

This study aimed at examining the influence of acute hypoxia on renin secretion and renin gene expression in the kidney. To this end, male Sprague-Dawley rats were exposed to severe hypoxic stress (8% O2) or to carbon monoxide (0.1% CO) for 6 h, and plasma renin activity (PRA) and renal renin mRNA levels were determined. PRA values increased from 3 to 13 and 10 ng angiotensin I x h(-1) x ml(-1), and renin mRNA levels increased by 120 and 100% during hypoxia and CO, respectively. Lowering the PO2 from 150 to 20 or 7 mmHg in the gas atmosphere of primary cultures of renal juxtaglomerular cells had no influence on renin secretion and renin gene expression after 6 and 20 h. Our findings thus suggest that both arterial and venous hypoxia can be powerful stimulators of renin secretion and renin gene expression in vivo. Because renal denervation did not prevent stimulation of the renin system by hypoxia, the effect could be indirectly mediated via the baroreceptor-macula densa mechanism. Another potential mediator of the effect could be circulating catecholamines, since we found that plasma norepinephrine increased from 0.7 to 1.5 and 2.4 ng/ml and plasma epinephrine increased from 0.3 to 1.4 and 2.7 ng/ml during hypoxia and CO inhalation, respectively.

Topics: Analysis of Variance; Angiotensin I; Animals; Carbon Monoxide; Cell Hypoxia; Cells, Cultured; Denervation; Epinephrine; Hypoxia; Juxtaglomerular Apparatus; Kidney; Male; Norepinephrine; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; Reference Values; Renin; RNA, Messenger; Transcription, Genetic

The plasma renin activity (RA), the concentration and the ratio of angiotensin (AI) conversion into angiotensin II (AII), and arginine vasopressin (AVP) level were observed in Wistar rats with pulmonary hypertension (PH) induced by extracardiac left-to-right shunting (LRS), hypobaric hypoxia (HH) and shunting plus HH (SHH). In comparison with normal control rats, RA in LRS and SHH rats showed an increasing trend, although no statistical significance appeared (P > 0.05). No change occurred in HH rats. The concentration and ratio of AI conversion into AII were significantly increased in LRS rats (P < 0.05), but decreased in HH and SHH rats (more markedly in HH rats). AVP increased significantly in LRS rats, and also showed an increasing trend in HH and SHH, but no significance was found (P > 0.05). The action of humoral factors in PH formation was discussed.

Topics: Angiotensin I; Angiotensin II; Animals; Arginine Vasopressin; Hypertension, Pulmonary; Hypoxia; Rats; Rats, Wistar; Renin; Renin-Angiotensin System

Dose-response curves of angiotensin I (AI, 1.0-1000.0 pmol) and angiotensin II (AII, 1.25-1250.00 pmol) were obtained in isolated rat hearts subjected to control conditions, mild hypoxia (PO2 = 145 mm Hg), reoxygenation, ischemic (perfusion pressure = 35 mm Hg) and reperfusion. Both AI and AII caused dose-dependent coronary flow (CF) of 26 +/- 3 and 27 +/- 2%, respectively. The effects of both AI and AII were substantially attenuated during hypoxia, but were fully restored upon reoxygenation. During ischemia, the effect of AII was unaltered while the effect of AI was enhanced compared to the control (P less than 0.05). This enhancement was reversible on reperfusion. Cardiac conversion of AI, calculated from ED50 values for AI and AII, was significantly increased during ischemia (P less than 0.05). Infusion of saralasin (0.5-5.0 micrograms/min) did not increase CF in any of the groups. We conclude that (1) the coronary vasoconstrictive effect of AII is preserved in ischemia but attenuated in hypoxia and (2) cardiac conversion of AI to AII is enhanced in hearts injured by ischemia.

Topics: Angiotensin I; Angiotensin II; Animals; Coronary Circulation; Coronary Disease; Coronary Vessels; Heart; Hypoxia; In Vitro Techniques; Male; Rats; Rats, Inbred Strains; Saralasin; Vasoconstriction

The coupling of aldosterone with renin is altered during acute hypoxemia. We measured the various components of the renin-angiotensin system and the plasma levels of immunoreactive atrial natriuretic factor (iANF) during room air and hypoxic gas-mixture breathing before and after administration of metoclopramide, a competitive antagonist of dopamine. Seven resting volunteers were studied 1 wk apart under room air and hypoxic conditions (inspired O2 fraction 0.12). During hypoxemia, the release of aldosterone induced by metoclopramide was significantly smaller. This change was associated with a slight increase in iANF and with a decrease in plasma angiotensin II levels, without any change in immunoreactive blood angiotensin I concentrations. Plasma electrolytes and blood acid-base status did not show relevant changes, nor did blood pressure and heart rate. We conclude that the decreased aldosterone concentrations seen under hypoxemia are related to decreased angiotensin II levels. Other influences, such as elevated ANF, may also mediate this effect.

Topics: Adult; Aldosterone; Angiotensin I; Angiotensin II; Atrial Natriuretic Factor; Blood Pressure; Heart Rate; Humans; Hypoxia; Metoclopramide; Oxygen; Potassium; Reference Values; Renin-Angiotensin System; Sodium

We compared the reactivity of pulmonary vessels to bradykinin (BK) and angiotensin I (AI) in normal and chronically hypoxic rats; the latter have pulmonary hypertension and muscularized pulmonary arterioles. These peptides are respectively inactivated and activated by the angiotensin converting-enzyme (ACE) on pulmonary endothelium. Isolated lungs were perfused at a constant flow rate when changes in pulmonary artery pressure (Ppa) reflect changes in vascular resistance. Dose-response curves to BK (1 ng-10 micrograms) were derived during normoxia and pre-constriction by hypoxia; BK both decreased and increased vascular resistance, i.e. vasodilation and vasoconstriction. In normal rats only constriction was seen in normoxia, which reflected low basal vascular tone, whereas in chronically hypoxic rats there was only dilatation which reflected high basal vascular tone. In hypoxia in normal rats, low doses caused dilatation, high doses constriction; in chronically hypoxic rats there was again only dilatation which was larger than in controls. After the ACE-inhibitor captopril, constriction was exaggerated in control rats in both normoxia and hypoxia and took place in chronically hypoxic rats after high doses in both normoxia and hypoxia; oedema often followed. Dose-response curves to AI (1 ng-micrograms) in normoxia showed greatly enhanced pressor responses in chronically hypoxic compared with normal rats, probably attributable to increased sensitivity to angiotensin II (AII) rather than enhanced conversion of AI to AII. Captopril caused a proportionate reduction in responses in both groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin I; Animals; Blood Pressure; Bradykinin; Captopril; Chronic Disease; Dose-Response Relationship, Drug; Hypoxia; Male; Pulmonary Artery; Rats; Rats, Inbred Strains; Vasoconstriction; Vasodilation

The high pressure muscular pulmonary circulation of chronically hypoxic (CH) rats was compared with the low pressure circuit in control (C) rats; differences were found in the effects of lung inflation, in pressure/flow relations during lung inflation, in reactivity to autocoids, and in responses to pulmonary dilator drugs. Isolated blood-perfused lungs of CH rats (2 to 3 wk in 10% O2) were compared with those of C rats kept in air. High inflation (alveolar) pressure (Palv) caused a rise in pulmonary artery pressure (Ppa) close to delta Palv in both groups; in CH rats, Ppa continued to rise, whereas it adapted to a lower level in C rats. Pressure-flow (P/Q) lines were measured at high and low Palv, all in Zone 2 state. In normoxia, high Palv caused a parallel shift in the P/Q line close to delta Palv in both C and CH rats. However, during hypoxic pulmonary vasoconstriction (HPV), high Palv caused a shift in the P/Q line less than delta Palv in C rats and greater than delta Palv in CH rats. Similar differences between C and CH rats were seen during constriction caused by almitrine, a drug that simulates HPV. Thus, these stimuli affect vessels that are functionally "extra-alveolar" in C rats but functionally "alveolar" in CH rats. We consider whether vasoconstriction by hypoxia and almitrine moves peripherally to the newly muscularized alveolar arterioles that are found in CH rats. Reactivity of lung vessels to bradykinin, angiotensin-1, and platelet-activating factor was greater in CH than in C rats, possibly also associated with muscularization of arterioles in the former.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine; Adenosine-5'-(N-ethylcarboxamide); Almitrine; Angiotensin I; Animals; Bradykinin; Chronic Disease; Hypoxia; Male; Platelet Activating Factor; Pulmonary Circulation; Pyrazines; Rats; Rats, Inbred Strains; Reference Values; Respiration; Vasoconstriction; Vasodilator Agents; Vasomotor System

The effects of exposing rats to hypoxia (10% O2) at normal atmospheric pressure for periods of 14 or 28 days on angiotensin-converting enzyme (ACE) activity and stores of angiotensin I (ANG I) and angiotensin II (ANG II) in lung, kidney, brain, and testis were examined. ACE activity was measured by spectrophotometric assay, and active sites of ACE were estimated by measuring the binding of 125I-351A [N-(1-carbonyl-3-phenyl-propyl)-L-lysyl-L-proline], a highly specific active site-directed inhibitor of ACE, to tissue homogenates and perfused lungs. Hypoxia exposure produced progressive reductions in ACE activity in lung homogenates and in ACE inhibitor binding to perfused lungs. ANG II levels in lungs from hypoxia-adapted animals were significantly less than air controls, suggesting that the reduction in intrapulmonary ACE activity was associated with reduced local generation of ANG II. ACE activity was increased in kidney and unchanged in brain and testis of hypoxia-adapted rats compared with air controls. Thus the effects of chronic hypoxia on catalytically active ACE and ACE active sites in the intact animal were organ specific. Adaptation to chronic hypoxia did not significantly alter plasma renin activity or ANG I or ANG II levels or serum ACE content. The hypoxia-induced alterations in lung and kidney ACE were reversible after return to a normoxic environment.

Topics: Adaptation, Physiological; Angiotensin I; Angiotensin II; Animals; Dipeptides; Enalapril; Hypoxia; Lisinopril; Lung; Male; Peptidyl-Dipeptidase A; Rats; Rats, Inbred Strains

Systemic and pulmonary vascular reactivity to graded doses of angiotensin I (ANG I), angiotensin II (ANG II), and, as a control, phenylephrine were examined in 14- or 28-day hypoxia-exposed and air control rats. Hypoxic rats exhibited pulmonary hypertension that was reversible on return to room air, but systemic arterial pressure was not altered by hypoxia. Systemic pressor responses to ANG I and ANG II were significantly less in the hypoxic rats than in the control rats at 14 and 28 days but returned to control levels in hypoxic animals that were then returned to room air, demonstrating reversibility of the hypoxia-induced changes in vascular reactivity. Pulmonary pressor responses to ANG I were significantly less at 14 days, whereas responses to ANG II were significantly greater at 28 days, in hypoxic rats than in controls. There were no significant differences in systemic and pulmonary pressor responses to phenylephrine between the hypoxic and air control animals. The altered systemic and pulmonary pressor responsiveness to ANG I and ANG II in hypoxic rats is probably related to mechanisms specific to the renin-angiotensin system, such as inhibition of intrapulmonary angiotensin-converting enzyme activity and down regulation of ANG II receptors in the systemic circulation. Further study is needed to elucidate these mechanisms.

Topics: Angiotensin I; Angiotensin II; Animals; Blood Pressure; Body Weight; Hypoxia; Male; Peptidyl-Dipeptidase A; Phenylephrine; Pulmonary Artery; Rats; Rats, Inbred Strains

Studies were initiated to investigate the effects of hypoxia on the conversion of angiotensin I (AI) to angiotensin II (AII) in microvessels of the lung. Using the technique of allografting neonatal lung tissue into the cheek pouch of normal hamsters, the microvessels of the lung, pulmonary arterioles, and venules could be visualized and manipulated by direct in vivo microscopy. The microvessels of the lung were studied 7-10 days after allografting by anesthetizing the hamster with pentobarbital (6.0 mg/100 g body weight i.p.) and then preparing the lung tissue for observation. The tissue was suffused with a Ringer's bicarbonate solution bubbled with a normal (20% O2-5% CO2-75% N2) or a low (95% N2-5% CO2) oxygen mixture. After equilibration, a pulmonary arteriole or venule was selected for observation, and the vessel geometry was recorded. Then, a micropipette containing either AI or AII was positioned alongside the vessel, and the agent was delivered continuously for 2 minutes. Lumen diameter was recorded continually for 8-10 minutes. This procedure was repeated until both angiotensins were tested on pulmonary arterioles and venules under conditions of a normal and low oxygen environment. This protocol was repeated on cheek pouch microvessels that did not contain pulmonary allografts. Both AI and AII produced rapid decreases in the lumen diameters of all microvessels tested. This vasoconstriction was greater for AII, and the oxygen environment did not alter the response. Conversion of AI to AII was not altered by the oxygen environment, and the relative conversion was similar in the microvessels of the lung and cheek pouch.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin I; Angiotensin II; Animals; Arteries; Arterioles; Cheek; Cricetinae; Female; Hypoxia; Lung; Lung Transplantation; Mesocricetus; Methods; Microcirculation; Peptidyl-Dipeptidase A; Pulmonary Circulation; Veins; Venules

The tissue protective effect of iloprost against anoxia was studied in the isolated perfused rat lung. The change in angiotensin converting enzyme activity was taken as a sign of the biochemical activity of pulmonary vascular endothelium and was measured by bioassay of the vasoconstrictor effects of angiotensin I and angiotensin II. A significant decrease in angiotensin converting enzyme activity was observed in the lungs incubated with Krebs alone and exposed to anoxia for 2 h. The decrease in angiotensin converting enzyme activity following anoxia for 2 and 24 h was prevented by prior pretreatment with iloprost. The pulmonary vasoconstrictor effect of angiotensin II was significantly enhanced following anoxia and iloprost prevented this potentiation. The prevention by iloprost of the decrease in angiotensin converting enzyme activity and increase in the pressor response to angiotensin II was attributed to damage of pulmonary vascular endothelium during anoxia. Possible underlying mechanisms are discussed.

Topics: Angiotensin I; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Epoprostenol; Female; Hypoxia; Iloprost; Lung; Male; Perfusion; Rats

The effects of exposing rats to hypoxia at normal atmospheric pressure for periods of 21-24 days on intrapulmonary conversion of angiotensin I (ANG I) to angiotensin II (ANG II) were examined using an isolated rat lung preparation perfused at constant flow. 125I-ANG I (160 fmol) was injected alone and with graded doses (0.1, 1.0, and 100 nmol) of unlabeled ANG I into the pulmonary artery, and the effluent was collected for measurement of ANG I, ANG II, and metabolites. At low doses of injected ANG I (125I-ANG I alone or with 0.1 or 1.0 nmol unlabeled ANG I), the percent conversion of ANG I to ANG II was 67.5 +/- 2.1 (SE), 65.1 +/- 2.0, and 62.5 +/- 1.6 in 21-day hypoxia-exposed animals and 83.8 +/- 2.7, 81.4 +/- 3.9, and 79.6 +/- 2.3 (P less than 0.01) in control rats maintained under normoxic conditions. At the highest dose (100 nmol) of injected ANG I, percent conversion was reduced in both hypoxic and control groups to 46.8 +/- 5.0 and 64.0 +/- 6.0, respectively (P less than 0.05). Mean transit times of labeled material through the pulmonary circulation were not significantly different in hypoxic vs. normoxic lungs at any ANG I load, suggesting that the decreased conversion seen in hypoxic lungs was not related to altered kinetics of substrate exposure. Thus chronic hypoxia is associated with significant inhibition of transpulmonary ANG I conversion that is independent of perfusate flow. We postulate that this phenomenon is due to alterations at the endothelial membrane level.

Topics: Angiotensin I; Angiotensin II; Angiotensins; Animals; Chronic Disease; Hypertension, Pulmonary; Hypoxia; In Vitro Techniques; Lung; Male; Peptidyl-Dipeptidase A; Perfusion; Pulmonary Circulation; Rats; Rats, Inbred Strains

Topics: Adult; Angiotensin I; Angiotensin II; Capillary Permeability; Female; Humans; Hypoxia; Infant, Newborn; Kallikreins; Kinins; Lung; Male; Renin-Angiotensin System; Respiratory Distress Syndrome, Newborn

Acute hypoxia in the intact animal and in cultured endothelial cells has been shown to be associated with a decrease in conversion of angiotensin I (AI) to angiotensin II (AII). Alterations in capillary surface and in contact time resulting from hemodynamic changes have been shown to influence the rate of pulmonary AI conversion. The dependency of AI conversion on hemodynamics complicates the interpretation of experiments showing changes in AI conversion in intact animals. We studied the effect of acute hypoxia on AI conversion in the isolated rat lung perfused at constant flow without recirculation of perfusate. Three levels of oxygenation were produced by ventilating lungs and equilibrating perfusate with a range of hypoxic gas mixtures. AI (1 microgram) was injected into the pulmonary artery, and the effluent was collected for measurement of AI and AII. Instead of the expected hypoxic inhibition, percent conversion of AI to AII increased slightly but significantly from 69.3 +/- 3.1 (mean +/- S.E.M.) at normal oxygenation to 74.4 +/- 3.0 at moderate hypoxia (P less than 0.005, paired t) and to 73.5 +/- 3.9 at severe hypoxia (P less than 0.01, paired t). Decreasing mean transit time of substrate through the lung (by increasing perfusate flow rate from 5 to 20 ml/min) resulted in a significant decrease in conversion of AI from 88.7 +/- 2.9 to 73.4 +/- 2.1% (P less than 0.001, paired t). These data confirm the effect of contact time on the rate of AI conversion in the lungs. The isolated rat lung preparation does not exhibit the phenomenon of hypoxia-induced inhibition of AI conversion. The authors speculate that hypoxia-induced inhibition of AI conversion in vivo may be secondary to the effects of hypoxia on hemodynamics.

Topics: Angiotensin I; Angiotensin II; Angiotensins; Animals; Biotransformation; Female; Hypoxia; Lung; Male; Perfusion; Rats; Rats, Inbred Strains

Evidence is presented implicating the renin-angiotensin system in the regulation of plasma erythropoietin concentration. Male and female rats were exposed to hypoxia at 0.43 atm for 8 hr. In male rats, individual erythropoietin values showed a positive correlation with renin, renin substrate, and angiotensin I after 8 hr of hypoxia. In female rats, renin was not elevated during hypoxia. However, after renin was injected subcutaneously, plasma renin values became similar to those in male rats and erythropoietin doubled. Individual erythropoietin values of the combined groups showed a positive correlation with plasma renin. A single oral dose of SQ 14225, an angiotensin I-converting enzyme inhibitor, reduced erythropoietin to undetectable levels in renin-injected female rats. Angiotensin II, in subpressor amounts, prevented the suppression of erythropoietin by SQ 14225. SQ 14225 also reduced renin substrate concentration at ambient pressure and during hypoxic exposure. The correlation coefficient between renin substrate and erythropoietin in rats given SQ 14225 to lower substrate or angiotensin II to increase substrate was 0.85; p < 0.0005. The increase in renin substrate that occurred during hypoxia in female rats given angiotensin II correlated positively with erythropoietin, r = 0.86; p < 0.0005.

Topics: Angiotensin I; Angiotensin II; Animals; Captopril; Erythropoietin; Female; Hypoxia; Male; Rats; Renin

We studied the effect of acute hypoxia on pulmonary conversion of angiotensin I to II in anesthetized dogs. When arterial PO2 was decreased from 86 +/- 14 (SD) to 33 +/- 8 mm Hg without changing pH or PCO2, the single passage conversion of intravenous boluses of radiolabeled angiotensin I in tracer doses fell significantly (P less than 0.005) from 72 +/- 4 to 67 +/- 6%. The effect of comparable levels of hypoxemia on the conversion of continuous intravenous infusions of pharmacological doses (1000 times physiological) of angiotensin I was greater: from 55 +/- 14 to 33 +/- 13% (P less than 0.025). There was prompt return of percent conversion ratios to control levels when hypoxemia was reversed. We conclude that acute hypoxia is associated with a reversible decrease in pulmonary angiotensin converting enzyme availability.

Topics: Acute Disease; Angiotensin I; Angiotensin II; Angiotensins; Animals; Blood Pressure; Carbon Dioxide; Cardiac Output; Dogs; Hydrogen-Ion Concentration; Hypoxia; Injections, Intravenous; Lung; Oxygen; Time Factors; Vasoconstriction

To determine if angiotension converting enzyme activity is altered by acute pathophysiological insults, we assessed angiotensin I conversion using a blood pressure response technique in anesthetized dogs studied during acute 100% O2 breathing and acute acid-base derangements. Also, we determined systemic vascular reactivity to angiotensin II by measuring the magnitude and duration of the arterial blood pressure response to intra-arterial injections of angiotensin II under these same conditions. Angiotensin I conversion found in normoxia [91 +/- 7 (SD)%] was unchanged by acute acidosis, alkalosis, and hyperoxia. During acute hyperoxia the mean half time of the hypertensive response increased from 68 +/- 25 (SD) s at a PaO2 of 112 +/- 18 (SD) Torr to 100 +/- 34 (SD) s at a PaO2 of 491 +/- 47 (SD) Torr (P less than 0.01). No other pathophysiological condition studied had any effect on reactivity of systemic vasculature to angiotensin II. We conclude that, except during acute hypoxia as previously shown, converting enzyme activity is resistant to other pathophysiological insults and that vascular responsiveness to angiotensin II is enhanced by hyperoxia.

Topics: Acid-Base Imbalance; Acidosis; Acidosis, Respiratory; Acute Disease; Alkalosis; Alkalosis, Respiratory; Angiotensin I; Angiotensin II; Angiotensins; Animals; Dogs; Hypoxia; Vascular Resistance

Topics: Angiotensin I; Angiotensins; Animals; Blood Pressure; Cardiac Output; Dogs; Hypoxia; Lung; Oxygen; Vascular Resistance

Topics: Angiotensin I; Angiotensin II; Angiotensins; Animals; Hypoxia; Lung; Prostaglandins; Prostaglandins E; Prostaglandins F; Pulmonary Alveoli; Rats; Vasomotor System