The Renin-Angiotensin System Modulates Inflammatory Processes in Atherosclerosis: Evidence from Basic Research and Clinical Studies

Recent evidence shows that the renin-angiotensin system is a crucial player in atherosclerotic processes. The regulation of arterial blood pressure was considered from its first description of the main mechanism involved. Vasoconstriction (mediated by angiotensin II) and salt and water retention (mainly due to aldosterone) were classically considered as pivotal proatherosclerotic activities. However, basic research and animal studies strongly support angiotensin II as a proinflammatory mediator, which directly induces atherosclerotic plaque development and heart remodeling. Furthermore, angiotensin II induces proatherosclerotic cytokine and chemokine secretion and increases endothelial dysfunction. Accordingly, the pharmacological inhibition of the renin-angiotensin system improves prognosis of patients with cardiovascular disease even in settings of normal baseline blood pressure. In the present review, we focused on angiotensin-convertingenzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and renin inhibitors to update the direct activities of the renin-angiotensin system in inflammatory processes governing atherosclerosis.

Download Full-text

Coevolution of the rennin–angiotensin system and the nervous control of blood circulation

Canadian Journal of Zoology ◽

10.1139/z84-022 ◽

1984 ◽

Vol 62 (2) ◽

pp. 137-147 ◽

Cited By ~ 6

Author(s):

John X. Wilson

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Blood Volume ◽

Vascular Resistance ◽

Renin Angiotensin System ◽

Peripheral Vascular Resistance ◽

Peripheral Vascular ◽

Angiotensin System ◽

Renin Angiotensin ◽

Arterial Blood

The mammalian renin–angiotensin system appears to be involved in the maintenance of blood volume and pressure because (i) sodium depletion, hypovolemia, and hypotension increase renin levels, and (ii) administration of exogenous angiotensin II rapidly increases mineralocorticoid and antidiuretic hormone production, transepithelial ion transport, drinking behavior, and peripheral vascular resistance. Are these also the physiological properties of the renin–angiotensin system in nonmammalian species? Signals for altered levels of renin activity have yet to be conclusively identified in nonmammalian vertebrates, but circulating renin levels are elevated by hypotension in teleost fish and birds. Systemic injection of angiotensin II causes an increase in arterial blood pressure in all the vertebrates studied, suggesting that barostatic control is a universal function of this hormone. Angiotensin II alters vascular tone by direct action on arteriolar muscles in some species, but at concentrations of the hormone which probably are unphysiological. More generally, angiotensin II increases blood pressure indirectly, by acting on the sympathetic nervous system. Catecholamines, derived from chromaffin cells and (or) from peripheral adrenergic nerves, mediate some portion of the vasopressor response to angiotensin II in cyclostomes, elasmobranchs, teleosts, amphibians, reptiles, mammals, and birds. Alteration of sympathetic outflow is a prevalent mechanism through which the renin–angiotensin system may integrate blood volume, cardiac output, and peripheral vascular resistance to achieve control of blood pressure and adequate perfusion of tissues.

Download Full-text

The Intrinsic Brain Iso-Renin-Angiotensin System in the Rat: Its Possible Role in Central Mechanisms of Blood Pressure Regulation

Clinical Science ◽

10.1042/cs048265s ◽

1974 ◽

Vol 48 (s2) ◽

pp. 265s-268s ◽

Cited By ~ 15

Author(s):

D. Ganten ◽

J. S. Hutchinson ◽

P. Schelling

Keyword(s):

Blood Pressure ◽

Cerebrospinal Fluid ◽

Angiotensin Ii ◽

Spontaneously Hypertensive Rats ◽

Renin Angiotensin System ◽

Angiotensin Ii Receptor ◽

Hypertensive Rats ◽

Angiotensin System ◽

Spontaneously Hypertensive ◽

Renin Angiotensin

1. Angiotensin is produced by the intrinsic iso-renin-angiotensin system. 2. Angiotensin is secreted into the cerebrospinal fluid of nephrectomized rats. 3. Angiotensin in cerebrospinal fluid elevates systemic blood pressure. 4. Rats with hereditary diabetes insipidus are virtually non-responsive to intraventricular angiotensin. 5. Angiotensin II is elevated in the cerebrospinal fluid of spontaneously hypertensive rats. 6. An intraventricular perfusion of the angiotensin II receptor-blocking agent P 113 decreases blood pressure in spontaneously hypertensive rats.

Download Full-text

The renin-angiotensin system in association with hyperreninaemic hypoaldosteronism in neoplasia induced hypercalcaemia

Acta Endocrinologica ◽

10.1530/acta.0.1020439 ◽

1983 ◽

Vol 102 (3) ◽

pp. 439-446

Author(s):

J. R. Sowers ◽

J. D. Barrett

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Serum Calcium ◽

Leydig Cell ◽

Renin Angiotensin System ◽

Plasma Norepinephrine ◽

Angiotensin System ◽

Renin Angiotensin ◽

Active Renin ◽

Arterial Blood

Abstract. The renin-angiotensin system was examined in Fischer rats at 7, 11 and 14 days after Leydig cell tumour transplantation and in age matched controls. Mean arterial blood pressure (MAP), active plasma renin and serum calcium were higher (P < 0.01) in the tumour transplant rats than in the controls at 11 days after transplantation. There was a positive correlation of both active renin and MAP with serum calcium at this time. Although inactive renin levels were elevated in the tumour transplanted rats, the ratio of inactive to active renin was decreased in comparison to controls. Plasma norepinephrine, active renin and plasma angiotensin II were higher in tumour rats at 14 days. Nevertheless, basal levels of aldosterone and MAP as well as aldosterone responses to graded infusion of angiotensin II, ACTH and KCl were decreased in the tumour rats at 14 days. Moderate hypercalcaemia (day 7 and 11), induced by Leydig cell transplantation in the Fischer rat, is associated, therefore with elevated blood pressure which appears to be related, in part, to activation of the reninangiotensin system. However, severe hypercalcaemia (day 14) was associated with hypotensive hyperreninaemic hypoaldosteronism state.

Download Full-text

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

Anesthesiology ◽

10.1097/00000542-200306000-00007 ◽

2003 ◽

Vol 98 (6) ◽

pp. 1338-1344 ◽

Cited By ~ 55

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.

Download Full-text

The Relationship between the Adrenal Tissue Renin-Angiotensin System, Internalization of the Type I Angiotensin II Receptor (AT1) and Angiotensin II Function in the Rat Adrenal Zona Glomerulosa Cell

Advances in Experimental Medicine and Biology - Tissue Renin-Angiotensin Systems ◽

10.1007/978-1-4899-0952-7_22 ◽

1995 ◽

pp. 319-329 ◽

Cited By ~ 6

Author(s):

G. P. Vinson ◽

M. M. Ho ◽

J. R. Puddefoot ◽

R. Teja ◽

S. Barker ◽

...

Keyword(s):

Angiotensin Ii ◽

Renin Angiotensin System ◽

Zona Glomerulosa ◽

Type I ◽

Angiotensin Ii Receptor ◽

Angiotensin System ◽

Renin Angiotensin ◽

Adrenal Tissue ◽

The Relationship

Download Full-text

Rosiglitazone, a Ligand to PPARγ, Improves Blood Pressure and Vascular Function through Renin-Angiotensin System Regulation

PPAR Research ◽

10.1155/2019/1371758 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 7

Author(s):

María Sánchez-Aguilar ◽

Luz Ibarra-Lara ◽

Leonardo Del Valle-Mondragón ◽

María Esther Rubio-Ruiz ◽

Alicia G. Aguilar-Navarro ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

In Silico ◽

Vascular Function ◽

Renin Angiotensin System ◽

Dependent Manner ◽

Insulin Sensitizer ◽

Angiotensin System ◽

Renin Angiotensin

Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPARγ) ligand, has been reported to act as insulin sensitizer and exert cardiovascular actions. In this work, we hypothesized that RGZ exerts a PPARγ–dependent regulation of blood pressure through modulation of angiotensin-converting enzyme (ACE)-type 2 (ACE2)/angiotensin-(1-7)/angiotensin II type-2 receptor (AT2R) axis in an experimental model of high blood pressure. We carried on experiments in normotensive (Sham) and aortic coarctation (AoCo)-induced hypertensive male Wistar rats. Both sham and AoCo rats were treated 7 days with vehicle (V), RGZ (5 mg/kg/day), or RGZ+BADGE (120 mg/kg/day) post-coarctation. We measured blood pressure and vascular reactivity on aortic rings, as well as the expression of renin-angiotensin system (RAS) proteins. We found that RGZ treatment in AoCo group decreases blood pressure values and improves vascular response to acetylcholine, both parameters dependent on PPARγ-stimulation. RGZ lowered serum angiotensin II (AngII) but increased Ang-(1-7) levels. It also decreased 8-hydroxy-2′-deoxyguanosine (8-OH-2dG), malondialdehyde (MDA), and improved the antioxidant capacity. Regarding protein expression of RAS, RGZ decreases ACE and angiotensin II type 1 receptor (AT1R) and improved ACE2, AT2R, and Mas receptor in AoCo rats. Additionally, an in silico analysis revealed that 5′UTR regions of RAS and PPARγ share motifs with a transcriptional regulatory role. We conclude that RGZ lowers blood pressure values by increasing the expression of RAS axis proteins ACE2 and AT2R, decreasing the levels of AngII and increasing levels of Ang-(1-7) in a PPARγ-dependent manner. The in silico analysis is a valuable tool to predict the interaction between PPARγ and RAS.

Download Full-text

Genetic knockdown of brain-derived neurotrophic factor in the nervous system attenuates angiotensin II-induced hypertension in mice

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/1470320319834406 ◽

2019 ◽

Vol 20 (1) ◽

pp. 147032031983440 ◽

Cited By ~ 1

Author(s):

Zhongming Zhang ◽

Yijing Zhang ◽

Yan Wang ◽

Shengchen Ding ◽

Chenhui Wang ◽

...

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Angiotensin Ii ◽

Renin Angiotensin System ◽

Subfornical Organ ◽

Angiotensin System ◽

Renin Angiotensin ◽

Peripheral Organs ◽

Induced Hypertension ◽

Basal Blood Pressure

Introduction: Brain-derived neurotropic factor (BDNF) is expressed throughout the central nervous system and peripheral organs involved in the regulation of blood pressure, but the systemic effects of BDNF in the control of blood pressure are not well elucidated. Materials and methods: We utilized loxP flanked BDNF male mice to cross with nestin-Cre female mice to generate nerve system BDNF knockdown mice, nestin-BDNF (+/–), or injected Cre adenovirus into the subfornical organ to create subfornical organ BDNF knockdown mice. Histochemistry was used to verify injection location. Radiotelemetry was employed to determine baseline blood pressure and pressor response to angiotensin II (1000 ng/kg/min). Real-time polymerase chain reaction was used to measure the expression of renin–angiotensin system components in the laminal terminalis and peripheral organs. Results: Nestin-BDNF (+/–) mice had lower renin–angiotensin system expression in the laminal terminalis and peripheral organs including the gonadal fat pad, and a lower basal blood pressure. They exhibited an attenuated hypertensive response and a weak or similar modification of renin–angiotensin system component expression to angiotensin II infusion. Subfornical organ BDNF knockdown was sufficient for the attenuation of angiotensin II-induced hypertension. Conclusion: Central BDNF, especially subfornical organ BDNF is involved in the maintenance of basal blood pressure and in augmentation of hypertensive response to angiotensin II through systemic regulation of the expression of renin–angiotensin system molecules.

Download Full-text