Pressor Response to Angiotensin I and Angiotensin II: The Site of Conversion of Angiotensin I

1972 ◽  
Vol 43 (6) ◽  
pp. 839-849 ◽  
Author(s):  
E. C. Osborn ◽  
G. Tildesley ◽  
P. T. Pickens
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Left Ventricular ◽  
Angiotensin I ◽  
Intravenous Injections ◽  
Pressor Responses ◽  
The Difference

1. The pressor responses to angiotensin I were compared with those to angiotensin II after injections into the left ventricle and jugular vein in the sheep, dog and pig. 2. The ability of angiotensin I to raise the blood pressure was less than that of angiotensin II with both routes of injection, a difference which was more marked after ventricular injection. 3. When equipressor doses of the hormones were given there was a delay of 1–3 s in the onset of the pressor response to angiotensin I compared with angiotensin II after left-ventricular injections; the difference in the delay in onset was less apparent with intravenous injections. 4. The development of the pressor responses was similar with both hormones when equipressor doses were used but the rises in blood pressure were more prolonged with angiotensin I, especially when given by the left-ventricular route. 5. The in vitro rate of activation of angiotensin I by blood was much slower than the apparent in vivo formation of angiotensin II.

In vitro and in vivo inhibition of renin by fatty acids.

1978 ◽  
Vol 234 (6) ◽  
pp. E593 ◽  
Author(s):  
T A Kotchen ◽  
W J Welch ◽  
R T Talwalkar
Keyword(s):  
Blood Pressure ◽  
Fatty Acids ◽  
Linoleic Acid ◽  
Angiotensin Ii ◽  
Neutral Lipids ◽  
Pressor Response ◽  
Arterial Blood ◽  
Arachidonic Acids

Circulating neutral lipids inhibit the in vitro renin reaction. To identify the inhibitor(s), free fatty acids were added to human renin and homologous substrate. Capric, lauric, palmitoleic, linoleic, and arachidonic acids each inhibited the rate of angiotensin I production in vitro (P less than 0.01). Inhibition by polysaturated fatty acids (linoleic and arachidonic) was less (P less than 0.01) after catalytic hydrogenation of the double bonds. To evaluate an in vivo effect of renin inhibition intra-arterial blood pressure responses to infusions of renin and angiotensin II (5.0 microgram) were measured in anephric rats (n = 6) before and after infusion of linoleic acid (10 mg iv). Mean increase of blood pressure to angiotensin II before (75 mmHg +/- 9) and after (90 +/- 12) linoleic acid did not differ (P greater than 0.05). However, the pressor response to renin after linoleic acid (18 +/- 3) was less (P less than 0.00)) than that before (102 +/- 13). In summary, several fatty acids inhibit the in vitro renin reaction, and in part inhibition is dependent on unsaturation. Linoleic acid also inhibits the in vivo pressor response to renin. These results suggest that fatty acids may modify the measurement of plasma renin activity and may also affect angiotensin production in vivo.

Selective inhibition of angiotensin II-mediated vasoconstriction by lipoxygenase blockade

1989 ◽  
Vol 257 (2) ◽  
pp. H434-H443 ◽  
Author(s):  
N. Stern ◽  
M. Golub ◽  
K. Nozawa ◽  
M. Berger ◽  
E. Knoll ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
High Performance ◽  
Pressor Response ◽  
Selective Inhibition ◽  
Ang Ii ◽  
Vascular Effects ◽  
Pressor Responses ◽  
Radiometric Detection

We have previously demonstrated that the lipoxygenase (LO) pathway has a specific role in the effect of angiotensin II (ANG II) on aldosterone secretion. To elucidate whether the LO pathway also participates in the vascular effects of ANG II, the nonselective LO inhibitor phenidone (PHE; 30 mg/kg) was administered to rats 1 h before graded dose ANG II infusion. PHE reduced the LO product 12-hydroxyeicosatetraenoic acid (12-HETE) in deendothelialized aortas by an average of 36% as determined by radiometric detection with high-performance liquid chromatography and radioimmunoassay methods. In parallel, the peak systolic pressor response to ANG II was lowered from 36.2 +/- 3.7 to 16.8 +/- 2.0 mmHg. The peak pressor responses to ANG II were also reduced by two other LO inhibitors, baicalein (30 mg/kg) and esculetin (60 mg/kg) (13.9 +/- 2.4 and 22.1 +/- 4.7 mmHg, respectively; P less than 0.01 compared with control rats for both), but not by the cyclooxygenase inhibitor indomethacin. The LO inhibitors baicalein (7.5 X 10(-5) M) and PHE (10(-4) M) markedly attenuated the in vitro contractile response to ANG II of femoral artery rings. In contrast, neither the in vivo nor in vitro constrictor responses to norepinephrine were affected by baicalein. Thus lipoxygenase blockade induces a direct and selective inhibition of ANG II-induced vasoconstriction. The LO pathway may have an important role in mediating the pressor effect of ANG II.

Abstract MP03: ROCK2 Specific Inhibition Attenuates Angiotensin II-induced Hypertension In Mice

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Daniel J Fehrenbach ◽  
Meena S Madhur
Keyword(s):  
Blood Pressure ◽  
T Cell ◽  
Angiotensin Ii ◽  
Repeated Measures ◽  
Flow Cytometric Analysis ◽  
Coiled Coil ◽  
Ang Ii ◽  
Induced Hypertension

Hypertension, or an elevated blood pressure, is the primary modifiable risk factor for cardiovascular disease, the number one cause of mortality worldwide. We previously demonstrated that Th17 activation and interleukin 17A (IL-17A)/IL-21 production is integral for the full development of a hypertensive phenotype as well as the renal and vascular damage associated with hypertension. Rho-associated coiled-coil containing protein Kinase 2 (ROCK2) serves as a molecular switch upregulating Th17 and inhibiting regulatory T cell (Treg) differentiation. We hypothesize that hypertension is characterized by excessive T cell ROCK2 activation leading to increased Th17/Treg ratios and ultimately end-organ damage. We first showed in vitro that KD025, an experimental orally bioavailable ROCK2 inhibitor inhibits Th17 cell proliferation and IL-17A/IL-21 production. To determine if hypertensive stimuli such as endothelial stretch increases T cell ROCK2 expression, we cultured human aortic endothelial cells exposed to 5% (normotensive) or 10% (hypertensive) stretch with circulating human T cells and HLA-DR+ antigen presenting cells. Hypertensive stretch increased T cell ROCK2 expression 2-fold. We then tested the effect of ROCK2 inhibition with KD025 (50mg/kg i.p. daily) in vivo on angiotensin II (Ang II)-induced hypertension. Treatment with KD025 significantly attenuated the hypertensive response within 1 week of Ang II treatment (systolic blood pressure: 139± 8 vs 108±7mmHg) and this persisted for the duration of the 4 week study reaching blood pressures 20 mmHg lower (135±13mmHg) than vehicle treated mice (158±4mmHg p<0.05 effect of treatment 2-way Repeated Measures ANOVA). Flow cytometric analysis of tissue infiltrating leukocytes revealed that KD025 treatment increased Treg/Th17 ratios in the kidney (0.61±0.03 vs 0.79±0.08, p<0.05 student’s t-test). Thus, T cell ROCK2 may be a novel therapeutic target for the treatment of hypertension.

Lipopolysaccharide induces apoptosis in adult rat ventricular myocytes via cardiac AT1 receptors

2002 ◽  
Vol 283 (2) ◽  
pp. H461-H467 ◽  
Author(s):  
Hai Ling Li ◽  
Jun Suzuki ◽  
Evelyn Bayna ◽  
Fu-Min Zhang ◽  
Erminia Dalle Molle ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ventricular Myocytes ◽  
Annexin V ◽  
Left Ventricular ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
Cardiac Apoptosis

Lipopolysaccharide (LPS) from gram-negative bacteria circulates in acute, subacute, and chronic conditions. It was hypothesized that LPS directly induces cardiac apoptosis. In adult rat ventricular myocytes (isolated with depyrogenated digestive enzymes to minimize tolerance), LPS (10 ng/ml) decreased the ratio of Bcl-2 to Bax at 12 h; increased caspase-3 activity at 16 h; and increased annexin V, propidium iodide, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining at 24 h. Apoptosis was blocked by the caspase inhibitor benzyloxycarbonyl-valine-alanine-aspartate fluoromethylketone (Z-VAD-fmk), captopril, and angiotensin II type 1 receptor (AT1) inhibitor (losartan), but not by inhibitors of AT2 receptors (PD-123319), tumor necrosis factor-α (TNFRII:Fc), or nitric oxide ( N G-monomethyl-l-arginine). Angiotensin II (100 nmol/l) induced apoptosis similar to LPS without additive effects. LPS in vivo (1 mg/kg iv) increased apoptosis in left ventricular myocytes for 1–3 days, which dissipated after 1–2 wk. Losartan (23 mg · kg−1 · day−1 in drinking water for 3 days) blocked LPS-induced in vivo apoptosis. In conclusion, low levels of LPS induce cardiac apoptosis in vitro and in vivo by activating AT1 receptors in myocytes.

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

scholarly journals Angiotensin II acts through the angiotensin 1a receptor to upregulate pendrin

2011 ◽  
Vol 301 (6) ◽  
pp. F1314-F1325 ◽  
Author(s):  
Jill W. Verlander ◽  
Seongun Hong ◽  
Vladimir Pech ◽  
James L. Bailey ◽  
Diana Agazatian ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Plasma Membrane ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Angiotensin Receptors ◽  
Apical Plasma Membrane ◽  
Protein Abundance ◽  
Wild Type ◽  
Induced Hypertension

Pendrin is an anion exchanger expressed in the apical regions of B and non-A, non-B intercalated cells. Since angiotensin II increases pendrin-mediated Cl− absorption in vitro, we asked whether angiotensin II increases pendrin expression in vivo and whether angiotensin-induced hypertension is pendrin dependent. While blood pressure was similar in pendrin null and wild-type mice under basal conditions, following 2 wk of angiotensin II administration blood pressure was 31 mmHg lower in pendrin null than in wild-type mice. Thus pendrin null mice have a blunted pressor response to angiotensin II. Further experiments explored the effect of angiotensin on pendrin expression. Angiotensin II administration shifted pendrin label from the subapical space to the apical plasma membrane, independent of aldosterone. To explore the role of the angiotensin receptors in this response, pendrin abundance and subcellular distribution were examined in wild-type, angiotensin type 1a (Agtr1a) and type 2 receptor (Agtr2) null mice given 7 days of a NaCl-restricted diet (< 0.02% NaCl). Some mice received an Agtr1 inhibitor (candesartan) or vehicle. Both Agtr1a gene ablation and Agtr1 inhibitors shifted pendrin label from the apical plasma membrane to the subapical space, independent of the Agtr2 or nitric oxide (NO). However, Agtr1 ablation reduced pendrin protein abundance through the Agtr2 and NO. Thus angiotensin II-induced hypertension is pendrin dependent. Angiotensin II acts through the Agtr1a to shift pendrin from the subapical space to the apical plasma membrane. This Agtr1 action may be blunted by the Agtr2, which acts through NO to reduce pendrin protein abundance.

Effect of Sodium Depletion on the Steroidogenic and Pressor Actions of Angiotensin in the Rat

1979 ◽  
Vol 56 (4) ◽  
pp. 325-333 ◽  
Author(s):  
W. B. Campbell ◽  
J. M. Schmitz ◽  
H. D. Itskovitz
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Sodium Depletion ◽  
Angiotensin I ◽  
Arterial Blood ◽  
Serum Aldosterone ◽  
Pressor Responses ◽  
Angiotensin Iii

1. To investigate the relative roles of angiotensin II (AII) and des-Asp1-angiotensin II (angiotensin III) in the control of blood pressure and aldosterone release, the effects of seven angiotensin agonists on mean arterial blood pressure and serum aldosterone concentrations were compared in normal and sodium-depleted, conscious rats. 2. In normal rats, angiotensin I, α-Asp1-angiotensin II, β-Asp1-angiotensin II, and angiotensin II-amide were equipotent in elevating mean arterial blood pressure. Angiotensin III, des-Asp1-angiotensin I, and poly-O-acetylserine-angiotensin II were 25%, 25%, and 41% as potent as angiotensin II, respectively. After sodium depletion, pressor responses to these angiotensin peptides were reduced approximately 60–80% when compared with control responses. In contrast, pressor responses to noradrenaline were not significantly affected by sodium depletion. 3. Angiotensin II, β-Asp1-angiotensin II, angiotensin II-amide, and angiotensin III were equipotent in increasing serum aldosterone concentrations in normal animals. Angiotensin I was 59% and des-Asp1-angiotensin I only 5% as potent as angiotensin II in their abilities to release aldosterone. After sodium depletion, control serum aldosterone concentrations increased as did the slope of the dose—response curve for each angiotensin peptide. Angiotensin II was the most potent steroidogenic peptide in sodium-depleted rats with angiotensin III and β-Asp1-angiotensin II being 27%, angiotensin I 7%, angiotensin II-amide 3%, and des-Asp1-angiotensin I 1% as potent as angiotensin II in releasing aldosterone. Poly-O-acetylserine-angiotensin II has less steroidogenic effect than angiotensin II or III in both normal and sodium-depleted animals. 4. Infusions of the angiotensin II antagonist, Sar1-Ile8-angiotensin II, and the angiotensin III antagonist, Ile7-angiotensin III, enhanced aldosterone release in normal rats without altering blood pressure. After sodium depletion, Sar1-Ile8-angiotensin II decreased blood pressure without affecting aldosterone release whereas Ile7-angiotensin III diminished aldosterone release without altering blood pressure. 5. These data suggest that angiotensin II, independent of its conversion into angiotensin III, is an important regulator of steroidogenesis in the rat in normal sodium states. In sodium depletion, the octapeptide retains significant steroidogenic activity; however, the contribution of angiotensin III to its steroidogenic effects is increased.

Role of nitric oxide resistance in erythropoietin-induced hypertension in rats with chronic renal failure

1996 ◽  
Vol 271 (1) ◽  
pp. E113-E122 ◽  
Author(s):  
N. D. Vaziri ◽  
X. J. Zhou ◽  
F. Naqvi ◽  
J. Smith ◽  
F. Oveisi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Chronic Renal Failure ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Magnesium Concentration ◽  
Induced Hypertension ◽  
Group A

We studied the mechanism of erythropoietin (EPO)-induced hypertension (HTN) in rats with chronic renal failure (CRF). After partial nephrectomy, rats were randomized into four groups. Group A received EPO, 150 U/kg, two times weekly for 6 wk to prevent anemia; group B received placebo injections and became anemic; group C received EPO but was kept anemic by dietary iron deficiency; and group D received placebo and regular transfusions to match hematocrit (Hct) in group A. Blood pressure (BP), Hct, platelet cytosolic calcium ([Ca2+]i) and magnesium concentration, and pressor and vasodilatory responses were determined. By design, Hct in groups A and D were comparable and significantly greater (P < 0.01) than in groups B and C. Despite divergent Hct values, the EPO-treated groups A and C showed a significant rise in BP compared with the placebo-treated groups B and D. HTN occurred whether EPO therapy was begun immediately or 4 wk after nephrectomy. EPO therapy augmented the elevation of basal [Ca2+]i and restored the defective thrombin-mediated rise of platelet [Ca2+]i in CRF animals. EPO therapy did not alter caudal artery contraction in response to either 68 mM K(+)-induced depolarization, angiotensin II or alpha 1-agonist, methoxamine in vitro, or the pressor response to angiotensin II in vivo. However, EPO therapy impaired the hypotensive response to nitric oxide (NO) donors, sodium nitroprusside and S-nitroso-N-acetyl-D,L-penicillamine, and reversed the CRF-induced upregulation of guanosine 3',5'-cyclic monophosphate production by thoracic aorta in vitro. Thus EPO-induced HTN in CRF rats is Hct independent and is associated with and perhaps causally related to increased basal and stimulated [Ca2+]i and impaired vasodilatory response to NO.

Angiotensin II formation in dog heart is mediated by different pathways in vivo and in vitro

1996 ◽  
Vol 271 (2) ◽  
pp. H417-H421 ◽  
Author(s):  
E. Balcells ◽  
Q. C. Meng ◽  
G. R. Hageman ◽  
R. W. Palmer ◽  
J. N. Durand ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Heart Tissue ◽  
Left Ventricular ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Ang Ii ◽  
Dog Heart ◽  
Tissue Extracts

Angiotensin-converting enzyme (ACE) inhibitors (I) have beneficial effects that are presumably mediated by decreased angiotensin II (ANG II) production. However, in vitro assays in human heart extracts have demonstrated that > 75% of ANG II-forming enzyme activity was not inhibited by captopril (Cap) and therefore did not appear to be related to ACE but was inhibited by chymostatin, suggesting that it was predominantly chymase-like activity. Previous work in our laboratory has demonstrated a similar relative contribution of ACE and chymase-like activity toward ANG II formation in vitro in dog heart tissue extracts. Accordingly, we compared Cap-inhibitable ANG II formation in vitro in heart tissue of five adult mongrel dogs to the in vivo Cap-inhibitable, ANG II-forming activity across the myocardial bed in four openchest, adult mongrel dogs. In vitro studies demonstrated that only 6 +/- 2% of ANG II formation was inhibited by Cap from heart tissue extracts of the left ventricular midwall. In in vivo studies, ANG I (0.5 nmol/min) followed by ANG I plus the ACE inhibitor Cap (0.1 mumol/min) was infused into the left anterior descending artery, and ANG II was assayed in the proximal aorta and coronary sinus. The arterial-venous (A-V) difference of ANG II across the myocardial circulation increased significantly during ANG I infusion (-13.4 +/- 23.5 to 142.8 +/- 71.4 pg/ml; P < 0.03). Subsequent coinfusion of Cap with ANG I significantly decreased the myocardial A-V difference of ANG II by 60 +/- 18% (P < 0.05). Thus, in contrast to the in vitro situation, ANG II formation in vivo is inhibited significantly by Cap in the normal dog heart. This comparison of in vivo and in vitro conversion of ANG I to ANG II by ACE and chymase-like activity suggests that in vitro assays may underestimate the functional contribution of ACE to intracardiac ANG II formation.

Comparative Pharmacology of New Specific Angiotensin Antagonists

1974 ◽  
Vol 48 (s2) ◽  
pp. 19s-21s
Author(s):  
B. A. Schoelkens
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Blood Pressure Response ◽  
Renal Hypertension ◽  
Antagonistic Activity ◽  
Conscious Rats ◽  
Blood Pressures ◽  
Colon Ascendens

1. The angiotensin II antagonism by newly synthesized 8-C-phenylglycine analogues of [5-isoleucine]angiotensin II in different preparations was investigated in vitro and in vivo. 2. All analogues competitively inhibited the myotropic effect of angiotensin II on the isolated colon ascendens of the guinea-pig and the stomach of the rat. 3. In normotensive dogs, cats, rabbits, guinea-pigs and rats the blood pressure response to infused angiotensin II was inhibited by the antagonists. The angiotensin II-induced fall in renal blood flow in the dog was blocked during infusion of the analogues. Acute renal hypertension in rats was significantly decreased. Of conscious rats variously with normal blood pressures, spontaneous hypertension and chronic renal hypertension, only in the last group could a marked uniform fall in blood pressure be demonstrated. The central pressor effect of angiotensin II was also inhibited in conscious rats. 4. 8-C-Phenylglycine analogues of [5-isoleucine]-angiotensin II exhibit a specific antagonistic activity to endogenous and exogenous angiotensin II.

Sign in / Sign up

Export Citation Format

Share Document