Inactivation of Bradykinin and Angiotensin I Conversion in Conscious Rats with Two-Kidney, One-Clip Hypertension

1982 ◽  
Vol 63 (s8) ◽  
pp. 199s-201s ◽  
Author(s):  
Inge E. K. Trindade ◽  
Eduardo M. Krieger
Keyword(s):  
Enzyme Activity ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Renal Artery ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Angiotensin I ◽  
Parallel Increase

1. The extents of pulmonary degradation of bradykinin (BK) and angiotensin I (ANG I) to angiotensin II (ANG II) conversion were measured simultaneously to determine whether converting enzyme activity, in vivo, is altered in two-kidney, one-clip hypertensive rats (15, 60 and 180 days after renal artery clipping). 2. Inactivation of BK (estimated by comparing equipressor doses injected intravenously and intra-aortically) was markedly increased in these hypertensive rats: 98.5% (15 days), 98.4% (60 days) and 99.5% (180 days) vs 95.6% in control rats. All groups of hypertensive rats exhibited hyper-reactivity to intra-aortic BK, requiring doses 14–38 times smaller than the control rats to produce the same depressor response. 3. The percentage of ANG I conversion (calculated from equipressor doses of ANG I and ANG II injected intravenously) was elevated after 15 days (46.0% vs 28.1% in control rats), unchanged after 60 days (27.7%) and slightly elevated after 180 days (36.0%). Hyporeactivity to ANG II was observed 15 and 180 days after renal artery clipping (doses six times were needed to produce a standard increase in mean arterial pressure). No alterations were found in the rats at 60 days after artery clipping. 4. The increased degradation of BK cannot be explained solely by elevation of converting enzyme activity since no parallel increase in ANG I conversion was observed, indicating that other bradykininases in the lung may be involved.

Angiotensin II induces apoptosis in human and rat alveolar epithelial cells

1999 ◽  
Vol 276 (5) ◽  
pp. L885-L889 ◽  
Author(s):  
Rongqi Wang ◽  
Alex Zagariya ◽  
Olivia Ibarra-Sunga ◽  
Claudia Gidea ◽  
Edmund Ang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Epithelial Cells ◽  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitor ◽  
Alveolar Epithelial Cells ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Alveolar Epithelial

Recent work from this laboratory demonstrated potent inhibition of apoptosis in human alveolar epithelial cells (AECs) by the angiotensin-converting enzyme inhibitor captopril [B. D. Uhal, C. Gidea, R. Bargout, A. Bifero, O. Ibarra-Sunga, M. Papp, K. Flynn, and G. Filippatos. Am. J. Physiol. 275 ( Lung Cell. Mol. Physiol. 19): L1013–L1017, 1998]. On this basis, we hypothesized that apoptosis in this cell type might be induced by angiotensin II (ANG II) through its interaction with the ANG II receptor. Purified ANG II induced dose-dependent apoptosis in both the human AEC-derived A549 cell line and in primary type II pneumocytes isolated from adult Wistar rats as detected by nuclear and chromatin morphology, caspase-3 activity, and increased binding of annexin V. Apoptosis also was induced in primary rat AECs by purified angiotensinogen. The nonselective ANG II-receptor antagonist saralasin completely abrogated both ANG II- and angiotensinogen-induced apoptosis at a concentration of 50 μg/ml. With RT-PCR, both cell types expressed the ANG II-receptor subtypes 1 and 2 and angiotensin-converting enzyme (ACE). The nonthiol ACE inhibitor lisinopril blocked apoptosis induced by angiotensinogen, but not apoptosis induced by purified ANG II. These data demonstrate the presence of a functional ANG II-dependent pathway for apoptosis in human and rat AECs and suggest a role for the ANG II receptor and ACE in the induction of AEC apoptosis in vivo.

scholarly journals Autophagy inhibition by chloroquine prevents increase in blood pressure and preserves endothelial functions

2020 ◽  
Vol 19 (4) ◽  
pp. 789-796
Author(s):  
Moon Jain ◽  
Hina Iqbal ◽  
Pankaj Yadav ◽  
Himalaya Singh ◽  
Debabrata Chanda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Angiotensin Ii ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Autophagy Flux ◽  
Endothelial Functions

Purpose: To determine the effects of lysosomal inhibition of autophagy by chloroquine (CHQ) onhypertension-associated changes in the endothelial functions. Method: Angiotensin II (Ang II)-treated human endothelial cell line EA.hy926 and renovascularhypertensive rats were subjected to CHQ treatment (in vitro: 0.5, 1, and 2.5 μM; in vivo: 50 mg/kg/dayfor three weeks). Changes in the protein expressions of LC3b II (autophagosome formation marker) andp62 (autophagy flux marker) were assessed using immunoblotting. Cell migration assay, tubuleformation assay (in vitro), and organ bath studies (in vivo) were performed to evaluate the endothelialfunctions. Hemodynamic parameters were measured as well. Results: A higher expression of LC3b II and a reduced expression of p62 observed in the Ang II-treatedendothelial cells, as well as in the aorta of the hypertensive rats, indicated enhanced autophagy.Treatment with CHQ resulted in reduced autophagy flux (in vitro as well as in vivo) and suppressed AngII-induced endothelial cell migration and angiogenesis (in vitro). The treatment with CHQ was alsoobserved to prevent increase in blood pressure in hypertensive rats and preserved acetylcholineinducedrelaxation in phenylephrine-contracted aorta from the hypertensive rats. In addition, chloroquineattenuated Ang II-induced contractions in the aorta of normotensive as well as hypertensive rats. Conclusion: These observations indicated that CHQ lowers the blood pressure and preserves thevascular endothelial function during hypertension. Keywords: Angiotensin II, Autophagy, Chloroquine, Endothelial function, Hypertension, Vasculardysfunction

Angiotensin I conversion and vascular reactivity in pathophysiological states in dogs

1980 ◽  
Vol 48 (2) ◽  
pp. 308-312 ◽  
Author(s):  
P. J. Leuenberger ◽  
S. A. Stalcup ◽  
L. M. Greenbaum ◽  
R. B. Mellins ◽  
G. M. Turino
Keyword(s):  
Blood Pressure ◽  
Enzyme Activity ◽  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Blood Pressure Response ◽  
Acute Hypoxia ◽  
Pressure Response ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Arterial Blood

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.

scholarly journals Electroacupuncture Improved Chronic Cerebral Hypoperfusion-Induced Anxiety-Like Behavior and Memory Impairments in Spontaneously Hypertensive Rats by Downregulating the ACE/Ang II/AT1R Axis and Upregulating the ACE2/Ang-(1-7)/MasR Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Peipei Feng ◽  
Zemin Wu ◽  
Hao Liu ◽  
Yafang Shen ◽  
Xu Yao ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Spontaneously Hypertensive Rats ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Memory Impairments

Electroacupuncture (EA) can effectively alleviate anxiety disorders and memory impairments caused by various neurodegenerative diseases; however, the molecular mechanisms underlying its neuroprotective effects are unclear. Previous studies have shown that the renin-angiotensin system (RAS) comprises of two axes with mutual antagonism: the classical angiotensin converting enzyme/angiotensin II/angiotensin II type 1 receptor (ACE/Ang II/AT1R) axis and the protective angiotensin converting enzyme 2/angiotensin-(1-7)/Mas receptor (ACE2/Ang-(1-7)/MasR) axis. In this study, we observed that chronic cerebral hypoperfusion (CCH) mediated anxiety-like behavior and memory impairments in spontaneously hypertensive rats (SHR) via upregulation of the hippocampal classical axis (ACE/Ang II/AT1R) and the partial hippocampal protective axis (ACE2/Ang-(1-7)). However, Ang II levels were much higher than those of Ang-(1–7), indicating that the ACE/Ang II/AT1R axis plays a dominant role in the comorbidity of CCH and hypertension. Moreover, candesartan cilexetil (Canc) and perindopril (Peril) were used as positive control drugs. We found that EA, Canc, and Peril attenuated CCH-induced anxiety-like behavior and memory impairments in SHR, potentially via downregulation of the hippocampal classical axis (ACE/Ang II/AT1R) and upregulation of the whole hippocampal protective axis (ACE2/Ang-(1-7)/MasR). These results suggest that EA therapy for CCH with hypertension may be mediated by two hippocampal RAS axes.

scholarly journals RENAL HYPERTENSION IN RATS IMMUNIZED AGAINST ANGIOTENSIN I AND ANGIOTENSIN II

1974 ◽  
Vol 139 (2) ◽  
pp. 239-248 ◽  
Author(s):  
Helen F. Oates ◽  
Gordon S. Stokes ◽  
Brian G. Storey ◽  
Robyn G. Glover ◽  
Beverley F. Snow
Keyword(s):  
Angiotensin Ii ◽  
Renal Artery ◽  
Mechanism Of Action ◽  
Renal Hypertension ◽  
Hypertensive Rats ◽  
Angiotensin I ◽  
Receptor Sites ◽  
Significant Difference ◽  
Blood Pressures ◽  
Renal Artery Constriction

Rats, actively immunized against angiotensin I (AI) and angiotensin II (AII), were subjected to unilateral renal artery constriction to determine whether the resulting hypertension, which may still ensue in the animal immunized against AII, could be prevented by such combined immunity. Sustained immunity to both AI and AII neither changed preoperative blood pressures of the rats from those of control mock-immunized rats nor altered the incidence or severity of renal dip hypertension. Vascular hyperresponsiveness to small quantities of free angiotensin could not be invoked to explain the hypertension, for there was no significant difference between mock-immunized hypertensive animals, and those remaining normotensive, regarding pressor sensitivity to intravenous AI, AII, renin, and norepinephrine. (AI + AII)-immunized hypertensive rats required AI doses averaging 260 times greater than nonimmune hypertensives to elicit equipressor responses, and were refractory to renin, but not to norepinephrine. Thus, while previous studies have not excluded direct participation of endogenous AI in renal clip hypertension in rats, evidence from our experiments makes it extremely difficult to sustain any pressor function therein for circulating AI or AII. Our results also preclude involvement of AII produced from circulating AI by conversion within arteriolar walls, close to receptor sites, since AI immunity would block this mechanism of action.

Functional role of local angiotensin-converting enzyme (ACE) in adrenal catecholamine secretion in vivo

1999 ◽  
Vol 77 (11) ◽  
pp. 878-885 ◽  
Author(s):  
Nobuharu Yamaguchi ◽  
Daniel Martineau ◽  
Stéphane Lamouche ◽  
Richard Briand
Keyword(s):  
Angiotensin Ii ◽  
Adrenal Gland ◽  
Angiotensin Converting Enzyme ◽  
Venous Blood Flow ◽  
Dependent Manner ◽  
Converting Enzyme ◽  
Left Adrenal Gland ◽  
Angiotensin I ◽  
Aortic Blood

The aim of the present study was to investigate whether exogenous angiotensin I (AngI) is locally converted to angiotensin II (AngII), which in turn results in an increase in the adrenal catecholamine (CA) secretion in the adrenal gland in anesthetized dogs. Plasma CA concentrations in adrenal venous and aortic blood were determined by an HPLC-electrochemical method. Adrenal venous blood flow was measured by gravimetry. Local administration of AngI (0.0062 to 6.2 µg, 0.0096 to 9.6 µM) to the left adrenal gland resulted in significant increases in CA output in a dose-dependent manner. Following administration of 0.62 µg (0.96 µM) of AngI, adrenal epinephrine and norepinephrine outputs increased from 20.8 ± 13.6 to 250.9 ± 96.4 ng·min-1·g-1 (p < 0.05, n = 5) and from 2.8 ± 1.7 to 29.6 ± 11.1 ng·min-1·g-1 (p < 0.05, n = 5), respectively. From the same left adrenal gland, the output of AngII increased from -0.02 ± 0.04 to 26.39 ± 11.38 ng·min-1·g-1 (p < 0.05, n = 5), while plasma concentrations of AngII in aortic blood remained unchanged. In dogs receiving captopril (12.5 µg, 0.5 mM) 10 min prior to AngI, the net amounts of CA and AngII secreted during the first 3 min after AngI were diminished by about 80% (p < 0.05, n = 5) compared with those obtained from the control group. There was a close correlation (r2 = 0.91, n = 6) between the net increases in AngII and CA outputs induced by AngI. The results indicate that the local angiotensin converting enzyme is functionally involved in regional AngII formation in the canine adrenal gland in vivo. The study suggests that AngII thus generated may play a role in the local regulation of adrenal CA secretion.Key words: angiotensin I, angiotensin II, captopril, adrenal gland, anesthetized dog.

Direct effects in vivo of angiotensins I and II on the canine sinus node

1991 ◽  
Vol 69 (3) ◽  
pp. 389-392 ◽  
Author(s):  
C. Lambert ◽  
D. Godin ◽  
P. Fortier ◽  
R. Nadeau
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Angiotensin Ii ◽  
Sinus Node ◽  
Converting Enzyme ◽  
Chronotropic Effect ◽  
Angiotensin I ◽  
Sinus Node Artery ◽  
Blood Pressures

The chronotropic responses to angiotensins I and II (5 μg in 1 mL Tyrode's solution) injected into the sinus node artery were assessed before and after the intravenous administration of captopril (2 mg/kg) and saralasin (20 μg/kg) in anaesthetized dogs. The effects of angiotensin II given intravenously were also observed. The animals (n = 8) were vagotomized and pretreated with propranolol (1 mg/kg, i.v.) to prevent baroreceptor-mediated responses to increases in blood pressure. Injection of angiotensin I into the sinus node artery induced significant increases in heart rate (114 ± 6 vs. 133 ± 6 beats/min) and in systemic systolic (134 ± 13 vs. 157 ± 14 mmHg; 1 mmHg = 133.3 Pa) and diastolic (95 ± 10 vs. 126 ± 13 mmHg) blood pressures. Similar results were obtained when angiotensin II was injected into the sinus node artery, but intravenous injection induced changes in systolic (138 ± 8 vs. 180 ± 25 mmHg) and diastolic (103 ± 8 vs. 145 ± 20 mmHg) blood pressures only. Captopril induced a significant decrease in systolic (118 ± 11 vs. 88 ± 12 mmHg) and diastolic (84 ± 9 vs. 59 ± 9 mmHg) blood pressures without affecting the heart rate (109 ± 6 vs. 106 ± 6 beats/min). Saralasin produced a significant increase in systolic (109 ± 7 vs. 126 ± 12 mmHg) blood pressure only. Increments in heart rate and systolic and diastolic blood pressures in response to angiotensins I and II were, respectively, abolished by captopril and saralasin. It was concluded that angiotensin II has, in vivo, a direct positive chronotropic effect that can be blocked by saralasin. The antagonism by captopril of the response to angiotensin I suggests the presence of local tissue converting enzyme activity in the region of the sinus node.Key words: angiotensin, chronotropic effect, tissue converting enzyme.

Protein kinase Cɛ contributes to regulation of the sarcolemmal Na+-K+ pump

2001 ◽  
Vol 281 (3) ◽  
pp. C1059-C1063 ◽  
Author(s):  
Kerrie A. Buhagiar ◽  
Peter S. Hansen ◽  
Nerida L. Bewick ◽  
Helge H. Rasmussen
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Enzyme Inhibitor ◽  
Pump Current ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Kinase C

A reduction in angiotensin II (ANG II) in vivo by treatment of rabbits with the angiotensin-converting enzyme inhibitor, captopril, increases Na+-K+ pump current ( I p) of cardiac myocytes. This increase is abolished by exposure of myocytes to ANG II in vitro. Because ANG II induces translocation of the ɛ-isoform of protein kinase C (PKCɛ), we examined whether this isozyme regulates the pump. We treated rabbits with captopril, isolated myocytes, and measured I p of myocytes voltage clamped with wide-tipped patch pipettes. I p of myocytes from captopril-treated rabbits was larger than I p of myocytes from controls. ANG II superfusion of myocytes from captopril-treated rabbits decreased I p to levels similar to controls. Inclusion of PKCɛ-specific blocking peptide in pipette solutions used to perfuse the intracellular compartment abolished the effect of ANG II. Inclusion of ψɛRACK, a PKCɛ-specific activating peptide, in pipette solutions had an effect on I p that was similar to that of ANG II. There was no additive effect of ANG II and ψɛRACK. We conclude that PKCɛ regulates the sarcolemmal Na+-K+ pump.

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