Signaling of angiotensin II-induced vascular protein synthesis in conduit and resistance arteries in vivo

We have compared the responsiveness of rabbit mesenteric resistance arteries with agonists under isometric and isobaric conditions. When pressurized (60 mmHg), arteries spontaneously reduced their diameter by 18.1%. An equivalent isometric stress did not generate force in a “wire” myograph. Subsequently, much higher concentrations of norepinephrine (NE) and histamine were required to cause isometric contractions than were needed to reduce vascular diameter of pressurized vessels, whereas angiotensin II produced a maintained response only in pressurized arteries. Reducing transmural pressure to 20 mmHg abolished pressure-induced myogenic tone and decreased arterial sensitivity to NE. Under isometric conditions, partial depolarization with KCl increased sensitivity to NE and histamine to within the concentration range effective in pressurized vessels and also "revealed" responses to angiotensin II. The membrane potential of the vascular smooth muscle cells under partially depolarized conditions was similar to that found in vivo and in vessels studied isobarically. These observations demonstrate a fundamental interaction between pressure-induced myogenic tone and the sensitivity of resistance arteries to vasoactive stimuli. This influence was mimicked in isometrically mounted vessels by partial depolarization, indicating a possible pivotal role for membrane potential in determining the reactivity of the resistance vasculature.

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Position of Src tyrosine kinases in the interaction between angiotensin II and endothelin in in vivo vascular protein synthesis

Journal of Hypertension ◽

10.1097/00004872-200502000-00015 ◽

2005 ◽

Vol 23 (2) ◽

pp. 329-335 ◽

Cited By ~ 4

Author(s):

Pierre Beaucage ◽

Marc Iglarz ◽

Marc Servant ◽

Rhian M Touyz ◽

Pierre Moreau

Keyword(s):

Protein Synthesis ◽

Angiotensin Ii ◽

Tyrosine Kinases ◽

Src Tyrosine Kinases

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EGF Receptor Transactivation in Angiotensin II and Endothelin Control of Vascular Protein Synthesis in vivo

Journal of Cardiovascular Pharmacology ◽

10.1097/01.fjc.0000166220.65593.22 ◽

2004 ◽

Vol 44 (Supplement 1) ◽

pp. S20-S23 ◽

Cited By ~ 8

Author(s):

Pierre Beaucage ◽

Pierre Moreau

Keyword(s):

Protein Synthesis ◽

Angiotensin Ii ◽

Egf Receptor ◽

Receptor Transactivation

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Angiotensin II increases the release of endothelin-I from human cultured endothelial cells but does not regulate its circulating levels

Clinical Science ◽

10.1042/cs0960261 ◽

1999 ◽

Vol 96 (3) ◽

pp. 261-270 ◽

Cited By ~ 1

Author(s):

Claudio FERRI ◽

Giovambattista DESIDERI ◽

Roberta BALDONCINI ◽

Cesare BELLINI ◽

Marco VALENTI ◽

...

Keyword(s):

Endothelial Cells ◽

Protein Synthesis ◽

Angiotensin Ii ◽

At1 Receptor ◽

Dependent Manner ◽

Synthesis Inhibitor ◽

Endothelin 1 ◽

Cultured Endothelial Cells

We investigated the effect of angiotensin II on endothelin-1 secretion in vitro and in vivo. In vivo, angiotensin II was given intravenously to 23 essential hypertensive and 8 control subjects according to different protocols: Study A, 1.0 ngċmin-1ċkg-1 and 3.0 ngċmin-1ċkg-1 angiotensin II for 30 min each; Study B, 1.0 ngċmin-1ċkg-1 and 3.0 ngċmin-1ċkg-1 angiotensin II for 120 min each; Study C, 3.0 ngċmin-1ċkg-1 angiotensin II for 30 min followed by a dose increment of 3.0 ngċmin-1ċkg-1 every 30 min until mean blood pressure levels increased by 25 mmHg; Study D, 1.0 ngċmin-1ċkg-1 followed by 3.0 ngċmin-1ċkg-1 angiotensin II for 60 min each on two different NaCl diets (either 20 mmol NaCl/day or 220 mmol NaCl/day, both for 1 week). In all in vivo studies neither plasma nor urine endothelin-1 levels changed with angiotensin II infusion. In contrast, angiotensin II (10-9, 10-8, 10-7 mol/l) stimulated endothelin-1 secretion from cultured human vascular endothelial cells derived from umbilical cord veins in a time- and dose-dependent manner. The in vitro angiotensin II effects were abolished by candesartan cilexetil, an inhibitor of the membrane-bound AT1 receptor, and also by actinomycin D, an RNA synthesis inhibitor, and cycloheximide, a protein synthesis inhibitor, indicating that endothelin-1 release depended on AT1 receptor subtype and de novo protein synthesis. Our findings indicate that angiotensin II regulates endothelin-1 release by cultured endothelial cells through an AT1 receptor-dependent pathway, but does not influence circulating endothelin-1 levels in vivo.

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Telomerase reverse transcriptase protects against angiotensin II-induced microvascular endothelial dysfunction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00472.2017 ◽

2018 ◽

Vol 314 (5) ◽

pp. H1053-H1060 ◽

Cited By ~ 15

Author(s):

Karima Ait-Aissa ◽

Andrew O. Kadlec ◽

Joseph Hockenberry ◽

David D. Gutterman ◽

Andreas M. Beyer

Keyword(s):

Cardiovascular Disease ◽

Angiotensin Ii ◽

Reverse Transcriptase ◽

Microvascular Dysfunction ◽

Telomerase Reverse Transcriptase ◽

Telomerase Rna ◽

Ang Ii ◽

Resistance Arteries ◽

Novel Target

A rise in reactive oxygen species (ROS) may contribute to cardiovascular disease by reducing nitric oxide (NO) levels, leading to loss of NO’s vasodilator and anti-inflammatory effects. Although primarily studied in larger conduit arteries, excess ROS release and a corresponding loss of NO also occur in smaller resistance arteries of the microcirculation, but the underlying mechanisms and therapeutic targets have not been fully characterized. We examined whether either of the two subunits of telomerase, telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC), affect microvascular ROS production and peak vasodilation at baseline and in response to in vivo administration to angiotensin II (ANG II). We report that genetic loss of TERT [maximal dilation: 52.0 ± 6.1% with vehicle, 60.4 ± 12.9% with Nω-nitro-l-arginine methyl ester (l-NAME), and 32.2 ± 12.2% with polyethylene glycol-catalase (PEG-Cat) ( P < 0.05), means ± SD, n = 9–19] but not TERC [maximal dilation: 79 ± 5% with vehicle, 10.7 ± 9.8% with l-NAME ( P < 0.05), and 86.4 ± 8.4% with PEG-Cat, n = 4–7] promotes flow-induced ROS formation. Moreover, TERT knockout exacerbates the microvascular dysfunction resulting from in vivo ANG II treatment, whereas TERT overexpression is protective [maximal dilation: 88.22 ± 4.6% with vehicle vs. 74.0 ± 7.3% with ANG II (1,000 ng·kg−1·min−1) ( P = not significant), n = 4]. Therefore, loss of TERT but not TERC may be a key contributor to the elevated microvascular ROS levels and reduced peak dilation observed in several cardiovascular disease pathologies. NEW & NOTEWORTHY This study identifies telomerase reverse transcriptase (TERT) but not telomerase RNA component as a key factor regulating endothelium-dependent dilation in the microcirculation. Loss of TERT activity leads to microvascular dysfunction but not conduit vessel dysfunction in first-generation mice. In contrast, TERT is protective in the microcirculation in the presence of prolonged vascular stress. Understanding the mechanism of how TERT protects against vascular stress represents a novel target for the treatment of vascular disorders.

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