Contribution of circulating renin to local synthesis of angiotensin peptides in the heart

2000 ◽  
Vol 4 (1) ◽  
pp. 67-73 ◽  
Author(s):  
GARY PRESCOTT ◽  
DAVID W. SILVERSIDES ◽  
SUI MEI LINDA CHIU ◽  
TIMOTHY L. REUDELHUBER
Keyword(s):  
Blood Pressure ◽  
Cardiac Fibrosis ◽  
Direct Evidence ◽  
Renin Angiotensin System ◽  
Local Synthesis ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Angiotensin Peptides ◽  
Specific Synthesis

The activity of a local cardiac renin-angiotensin system (RAS) has long been suspected in the promotion of cardiac pathologies including hypertrophy, ischemia, and infarction. All of the components of the RAS cascade have been demonstrated to be synthesized within the heart with the possible exception of the first enzyme in the cascade, renin. In the current study, we provide direct evidence that circulating renin can contribute to cardiac-specific synthesis of angiotensin peptides. Furthermore, we demonstrate this effect is independent of blood pressure and that in animals of comparable blood pressure, elevated circulating renin significantly enhances cardiac fibrosis. These results may serve to explain some of the cardiac pathologies associated with the RAS.

scholarly journals Dipeptidyl peptidase 3 modulates the renin–angiotensin system in mice

2020 ◽  
Vol 295 (40) ◽  
pp. 13711-13723 ◽  
Author(s):  
Shalinee Jha ◽  
Ulrike Taschler ◽  
Oliver Domenig ◽  
Marko Poglitsch ◽  
Benjamin Bourgeois ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renin Angiotensin System ◽  
Dipeptidyl Peptidase ◽  
Amino Acid Residues ◽  
Angiotensin System ◽  
Ras Pathway ◽  
Renin Angiotensin ◽  
Cell Defense ◽  
Angiotensin Peptides ◽  
Dipeptidyl Peptidase 3

Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase involved in degrading oligopeptides with 4–12 amino acid residues. It has been associated with several pathophysiological processes, including blood pressure regulation, pain signaling, and cancer cell defense against oxidative stress. However, the physiological substrates and the cellular pathways that are potentially targeted by DPP3 to mediate these effects remain unknown. Here, we show that global DPP3 deficiency in mice (DPP3−/−) affects the renin–angiotensin system (RAS). LC–MS–based profiling of circulating angiotensin peptides revealed elevated levels of angiotensin II, III, IV, and 1–5 in DPP3−/− mice, whereas blood pressure, renin activity, and aldosterone levels remained unchanged. Activity assays using the purified enzyme confirmed that angiotensin peptides are substrates for DPP3. Aberrant angiotensin signaling was associated with substantially higher water intake and increased renal reactive oxygen species formation in the kidneys of DPP3−/− mice. The metabolic changes and altered angiotensin levels observed in male DPP3−/− mice were either absent or attenuated in female DPP3−/− mice, indicating sex-specific differences. Taken together, our observations suggest that DPP3 regulates the RAS pathway and water homeostasis by degrading circulating angiotensin peptides.

scholarly journals Novel angiotensin peptides regulate blood pressure, endothelial function, and natriuresis.

1998 ◽  
Vol 9 (9) ◽  
pp. 1716-1722
Author(s):  
C M Ferrario ◽  
M C Chappell ◽  
R H Dean ◽  
S N Iyer
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Receptor Subtype ◽  
Angiotensin I ◽  
Blood Pressure Lowering Effect ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Angiotensin Peptides ◽  
Pressure Lowering

Accumulating evidence suggests that angiotensin-(1-7) is an important component of the renin-angiotensin system, having actions that are either identical to or opposite that of angiotensin II. Angiotensin I can be directly converted to angiotensin-(1-7), bypassing formation of angiotensin II. This pathway is under the control of three enzymes: neutral endopeptidases 24.11 (neprilysin) and 24.15 and prolyl-endopeptidase 24.26. Two of the three angiotensin-forming enzymes (neprilysin and endopeptidase 24.15) also contribute to the breakdown of bradykinin and the atrial natriuretic peptide. Furthermore, angiotensin-(1-7) is a major substrate for angiotensin-converting enzyme. These observations suggest that the process of biotransformation between the various Ang peptides of the renin-angiotensin system and other vasodepressor peptides are intertwined through this enzymatic pathway. Substantial evidence suggests that angiotensin-(1-7) stimulates the synthesis and release of vasodilator prostaglandins, and nitric oxide, while also augmenting the metabolic actions of bradykinin. In addition, angiotensin-(1-7) alters tubular sodium and bicarbonate reabsorption, decreases Na+-K+-ATPase activity, induces diuresis, and exerts a vasodilator effect. These physiologic effects of angiotensin-(1-7) favor a blood pressure-lowering effect. The majority of the data currently available suggest that angiotensin-(1-7) mediates its effects through a novel non-AT1/AT2 receptor subtype.

Terlipressin Versus  Norepinephrine to Correct Refractory Arterial Hypotension after General Anesthesia in Patients Chronically Treated with Renin-Angiotensin System Inhibitors

2003 ◽  
Vol 98 (6) ◽  
pp. 1338-1344 ◽  
Author(s):  
Gilles Boccara ◽  
Alexandre Ouattara ◽  
Gilles Godet ◽  
Eric Dufresne ◽  
Michèle Bertrand ◽  
...  
Keyword(s):  
Blood Pressure ◽  
General Anesthesia ◽  
Arterial Blood Pressure ◽  
Renin Angiotensin System ◽  
Arterial Hypotension ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Arterial Blood ◽  
Long Term Treatment ◽  
Systolic Arterial Blood Pressure

Background Terlipressin, a precursor that is metabolized to lysine-vasopressin, has been proposed as a drug for treatment of intraoperative arterial hypotension refractory to ephedrine in patients who have received long-term treatment with renin-angiotensin system inhibitors. The authors compared the effectiveness of terlipressin and norepinephrine to correct hypotension in these patients. Methods Among 42 patients scheduled for elective carotid endarterectomy, 20 had arterial hypotension following general anesthesia that was refractory to ephedrine. These patients were the basis of the study. After randomization, they received either 1 mg intravenous terlipressin (n = 10) or norepinephrine infusion (n = 10). Beat-by-beat recordings of systolic arterial blood pressure and heart rate were stored on a computer. The intraoperative maximum and minimum values of blood pressure and heart rate, and the time spent with systolic arterial blood pressure below 90 mmHg and above 160 mmHg, were used as indices of hemodynamic stability. Data are expressed as median (95% confidence interval). Results Terlipressin and norepinephrine corrected arterial hypotension in all cases. However, time spent with systolic arterial blood pressure below 90 mmHg was less in the terlipressin group (0 s [0-120 s] vs. 510 s [120-1011 s]; P < 0.001). Nonresponse to treatment (defined as three boluses of terlipressin or three changes in norepinephrine infusion) occurred in zero and eight cases (P < 0.05), respectively. Conclusions In patients who received long-term treatment with renin-angiotensin system inhibitors, intraoperative refractory arterial hypotension was corrected with both terlipressin and norepinephrine. However, terlipressin was more rapidly effective for maintaining normal systolic arterial blood pressure during general anesthesia.

scholarly journals Divergent mechanism regulating fluid intake and metabolism by the brain renin-angiotensin system

2012 ◽  
Vol 302 (3) ◽  
pp. R313-R320 ◽  
Author(s):  
Curt D. Sigmund
Keyword(s):  
Blood Pressure ◽  
Fluid Intake ◽  
Renin Angiotensin System ◽  
Metabolic Effects ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Intracellular Form ◽  
Efferent Pathways ◽  
The Brain ◽  
Pituitary Adrenal Axis

The purpose of this review is two-fold. First, I will highlight recent advances in our understanding of the mechanisms regulating angiotensin II (ANG II) synthesis in the brain, focusing on evidence that renin is expressed in the brain and is expressed in two forms: a secreted form, which may catalyze extracellular ANG I generation from glial or neuronal angiotensinogen (AGT), and an intracellular form, which may generate intracellular ANG in neurons that may act as a neurotransmitter. Second, I will discuss recent studies that advance the concept that the renin-angiotensin system (RAS) in the brain not only is a potent regulator of blood pressure and fluid intake but may also regulate metabolism. The efferent pathways regulating the blood pressure/dipsogenic effects and the metabolic effects of elevated central RAS activity appear different, with the former being dependent upon the hypothalamic-pituitary-adrenal axis, and the latter being dependent upon an interaction between the brain and the systemic (or adipose) RAS.

Renin-angiotensin system in stroke-prone spontaneously hypertensive rats

1979 ◽  
Vol 236 (3) ◽  
pp. H409-H416 ◽  
Author(s):  
M. Shibota ◽  
A. Nagaoka ◽  
A. Shino ◽  
T. Fujita
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Malignant Hypertension ◽  
Hypertensive Rats ◽  
Salt Loading ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Renin Angiotensin

The development of malignant hypertension was studied in stroke-prone spontaneously hypertensive rats (SHR) kept on 1% NaCl as drinking water. Along with salt-loading, blood pressure gradually increased and reached a severe hypertensive level (greater than 230 mmHg), which was followed by increases in urinary protein (greater than 100 (mg/250 g body wt)/day) and plasma renin concentration (PRC, from 18.9 +/- 0.1 to 51.2 +/- 19.4 (ng/ml)/h, mean +/- SD). At this stage, renal small arteries and arterioles showed severe sclerosis and fibrinoid necrosis. Stroke was observed within a week after the onset of these renal abnormalities. The dose of exogenous angiotensin II (AII) producing 30 mmHg rise in blood pressure increased with the elevation of PRC, from 22 +/- 12 to 75 +/- 36 ng/kg, which was comparable to that in rats on water. The fall of blood pressure due to an AII inhibitor, [1-sarcosine, 8-alanine]AII (10(microgram/kg)/min for 40 min) became more prominent with the increase in PRC in salt-loaded rats, but was not detected in rats on water. These findings suggest that the activation of renin-angiotensin system participates in malignant hypertension of salt-loaded stroke-prone SHR rats that show stroke signs, proteinuria, hyperreninemia, and renovascular changes.

Sign in / Sign up

Export Citation Format

Share Document