Expression of renin-angiotensin system and extracellular matrix genes in cardiovascular cells and its regulation through AT1 receptor

2000 ◽  
pp. 203-209
Author(s):  
Kouichi Tamura ◽  
Yuqing E. Chen ◽  
Qin Chen ◽  
Nobuo Nyui ◽  
Masatsugu Horiuchi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Renin Angiotensin System ◽  
At1 Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Cardiovascular Cells

The renin–angiotensin system, bone marrow and progenitor cells

2012 ◽  
Vol 123 (4) ◽  
pp. 205-223 ◽  
Author(s):  
Matej Durik ◽  
Bruno Sevá Pessôa ◽  
Anton J. M. Roks
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Angiotensin Ii ◽  
Progenitor Cells ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Cardiovascular Therapy ◽  
Cardiovascular Cells ◽  
Stimulation Of

Modulation of the RAS (renin–angiotensin system), in particular of the function of the hormones AngII (angiotensin II) and Ang-(1–7) [angiotensin-(1–7)], is an important target for pharmacotherapy in the cardiovascular system. In the classical view, such modulation affects cardiovascular cells to decrease hypertrophy, fibrosis and endothelial dysfunction, and improves diuresis. In this view, excessive stimulation of AT1 receptors (AngII type 1 receptors) fulfils a detrimental role, as it promotes cardiovascular pathogenesis, and this is opposed by stimulation of the AT2 receptor (angiotensin II type 2 receptor) and the Ang-(1–7) receptor encoded by the Mas proto-oncogene. In recent years, this view has been broadened with the observation that the RAS regulates bone marrow stromal cells and stem cells, thus involving haematopoiesis and tissue regeneration by progenitor cells. This change of paradigm has enlarged the field of perspectives for therapeutic application of existing as well as newly developed medicines that alter angiotensin signalling, which now stretches beyond cardiovascular therapy. In the present article, we review the role of AngII and Ang-(1–7) and their respective receptors in haematopoietic and mesenchymal stem cells, and discuss possible pharmacotherapeutical implications.

Modification of the pulmonary renin–angiotensin system and lung structural remodelling in congestive heart failure

2006 ◽  
Vol 111 (3) ◽  
pp. 217-224 ◽  
Author(s):  
Frederic Lefebvre ◽  
Annick Préfontaine ◽  
Angelino Calderone ◽  
Alexandre Caron ◽  
Jean-François Jasmin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Renin Angiotensin System ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Coronary Artery Ligation ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Lung Remodelling

Lung structural remodelling, characterized by myofibroblast proliferation and collagen deposition, contributes to impaired functional capacity in CHF (congestive heart failure). As the lung is the primary site for the formation of Ang II (angiotensin II), local modifications of this system could contribute to lung remodelling. Rats with CHF, induced following myocardial infarction (MI) via coronary artery ligation, were compared with sham-operated controls. The MI group developed lung remodelling as confirmed by morphometric measurements and immunohistochemistry. Pulmonary Ang II concentrations increased more than 6-fold (P<0.01), and AT1 (Ang II type 1) receptor expression was elevated by 3-fold (P<0.01) with evidence of distribution in myofibroblasts. AT2 (Ang II type 2) receptor expression was unchanged. In isolated lung myofibroblasts, AT1 and AT2 receptors were expressed, and Ang II stimulated proliferation as measured by [3H]thymidine incorporation. In normal rats, chronic intravenous infusion of Ang II (0.5 mg·kg−1 of body weight·day−1) for 28 days significantly increased mean arterial pressure (P<0.05), without pulmonary hypertension, lung remodelling or a change in AT1 receptor expression. We conclude that there is a modification of the pulmonary renin–angiotensin system in CHF, with increased Ang II levels and AT1 receptor expression on myofibroblasts. Although this may contribute to lung remodelling, the lack of effect of increased plasma Ang II levels alone suggests the importance of local pulmonary Ang II levels combined with the effect of other factors activated in CHF.

scholarly journals Involvement of the Intrarenal Renin-Angiotensin System in Experimental Models of Glomerulonephritis

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Maki Urushihara ◽  
Yukiko Kinoshita ◽  
Shuji Kondo ◽  
Shoji Kagami
Keyword(s):  
Blood Pressure ◽  
Intracellular Signaling ◽  
Renin Angiotensin System ◽  
Experimental Models ◽  
At1 Receptor ◽  
Biologically Active ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Proinflammatory Mediators

The intrarenal renin-angiotensin system (RAS) has several pathophysiologic functions not only in blood pressure regulation but also in the development of glomerulonephritis (GN). Angiotensin II (Ang II) is the biologically active product of the RAS. Locally produced Ang II induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation, regulates the gene expression of bioactive substances, and activates multiple intracellular signaling pathways, leading to tissue damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, cell proliferation, and extracellular matrix synthesis, which facilitates glomerular injury. Previous studies have shown that angiotensin-converting enzyme inhibitors and/or AT1 receptor blockers have beneficial effects in experimental GN models and humans with various types of GN, and that these effects are more significant than their suppressive effects on blood pressure. In this paper, we focus on intrarenal RAS activation in the pathophysiology of experimental models of GN.

Inhibition of the renin–angiotensin system prevents seizures in a rat model of epilepsy

2010 ◽  
Vol 119 (11) ◽  
pp. 477-482 ◽  
Author(s):  
Marilia G.A.G. Pereira ◽  
Christiane Becari ◽  
José A.C. Oliveira ◽  
Maria Cristina O. Salgado ◽  
Norberto Garcia-Cairasco ◽  
...  
Keyword(s):  
Rat Model ◽  
Hormone Secretion ◽  
Renin Angiotensin System ◽  
Epileptic Seizures ◽  
At1 Receptor ◽  
Electrolyte Balance ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Central Nervous System

The RAS (renin–angiotensin system) is classically involved in BP (blood pressure) regulation and water–electrolyte balance, and in the central nervous system it has been mostly associated with homoeostatic processes, such as thirst, hormone secretion and thermoregulation. Epilepsies are chronic neurological disorders characterized by recurrent epileptic seizures that affect 1–3% of the world's population, and the most commonly used anticonvulsants are described to be effective in approx. 70% of the population with this neurological alteration. Using a rat model of epilepsy, we found that components of the RAS, namely ACE (angiotensin-converting enzyme) and the AT1 receptor (angiotensin II type 1 receptor) are up-regulated in the brain (2.6- and 8.2-fold respectively) following repetitive seizures. Subsequently, epileptic animals were treated with clinically used doses of enalapril, an ACE inhibitor, and losartan, an AT1 receptor blocker, leading to a significant decrease in seizure severities. These results suggest that centrally acting drugs that target the RAS deserve further investigation as possible anticonvulsant agents and may represent an additional strategy in the management of epileptic patients.

Cardiovascular hypertrophy in diabetic spontaneously hypertensive rats: optimizing blockade of the renin–angiotensin system

2003 ◽  
Vol 104 (4) ◽  
pp. 341-347 ◽  
Author(s):  
Markus LASSILA ◽  
Belinda J. DAVIS ◽  
Terri J. ALLEN ◽  
Louise M. BURRELL ◽  
Mark E. COOPER ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Calcium Channel ◽  
Spontaneously Hypertensive Rats ◽  
Renin Angiotensin System ◽  
At1 Receptor ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Renin Angiotensin

The aim of the present study was to compare the antihypertrophic effects of blockade of the renin–angiotensin system (RAS), vasopeptidase inhibition and calcium channel antagonism on cardiac and vascular hypertrophy in diabetic spontaneously hypertensive rats (SHR). SHR with streptozotocin-induced diabetes were treated with one of the following therapies for 32 weeks: the angiotensin-converting enzyme (ACE) inhibitor captopril (100mg/kg); the angiotensin AT1 receptor antagonist valsartan (30mg/kg); a combination of captopril with valsartan; the vasopeptidase inhibitor mixanpril (100mg/kg); or the calcium channel antagonist amlodipine (6mg/kg). Systolic blood pressure and cardiac and mesenteric artery hypertrophy were assessed. Mean systolic blood pressure in diabetic SHR (200±5mmHg) was reduced by captopril (162±5mmHg), valsartan (173±5mmHg), mixanpril (176±2mmHg) and amlodipine (159±4mmHg), and was further reduced by the combination of captopril with valsartan (131±5mmHg). Captopril, valsartan and mixanpril reduced heart and left ventricle weights by approx. 10%. The combination of captopril and valsartan further reduced heart weight (-24%) and left ventricular weight (-29%). Amlodipine did not affect cardiac hypertrophy. Only mixanpril and the combination of captopril and valsartan significantly reduced mesenteric weight. The mesenteric wall/lumen ratio was reduced by all drugs, and to a greater extent by the combination of captopril and valsartan. We conclude that optimizing the blockade of vasoconstrictive pathways such as the RAS, particularly with the combination of ACE inhibition and AT1 receptor antagonism, is associated with antitrophic effects in the context of diabetes and hypertension. In contrast, calcium channel blockade, despite similar effects on blood pressure, confers less antitrophic effects in the diabetic heart and blood vessels.

Renin-angiotensin system modulates renal bradykinin production

1996 ◽  
Vol 271 (4) ◽  
pp. R1090-R1095 ◽  
Author(s):  
H. M. Siragy ◽  
A. A. Jaffa ◽  
H. S. Margolius ◽  
R. M. Carey
Keyword(s):  
Renal Plasma Flow ◽  
Renin Angiotensin System ◽  
At1 Receptor ◽  
Sodium Depletion ◽  
Kinin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System ◽  
Cgmp Formation

Previous studies have shown that sodium depletion is associated with an increase in renal kallikrein-kinin system activity. This system may play an important role in counterbalancing the renal effects of the renin-angiotensin system. In this study, we examined whether the renal renin-angiotensin system participates in the regulation of renal bradykinin (BK) levels during sodium depletion. We measured changes in renal excretory and hemodynamic function, renal interstitial fluid (RIF) BK, and RIF and urinary guanosine 3',5'-cyclic monophosphate (cGMP) and prostaglandin E2 (PGE2) in conscious uninephrectomized dogs (n = 5) in sodium metabolic balance (10 meq/day) in response to intrarenal arterial administration of the renin inhibitor ACRIP (0.2 microgram.kg-1.min-1) or angiotensin II AT1-receptor blocker losartan (100 ng.kg-1.min-1). ACRIP and losartan increased urine flow rate from 0.75 +/- 0.06 to 1.6 +/- 0.03 and 1.5 +/- 0.05 ml/min, respectively (each P < 0.001), and urine sodium excretion from 5.4 +/- 0.7 to 18.3 +/- 1.3 and 15.9 +/- 1.2 meq/min, respectively (each P < 0.001). Glomerular filtration rate and renal plasma flow increased only during losartan administration (P < 0.05). ACRIP decreased RIF BK by 48%, from 33.1 +/- 3.8 to 17.4 +/- 4.1 pg/min (P < 0.01). ACRIP decreased RIF cGMP by 38%, from 0.69 +/- 0.08 to 0.43 +/- 0.1 pmol/min (P < 0.01); urinary cGMP by 16%, from 0.63 +/- 0.05 to 0.53 +/- 0.02 pmol/min (P < 0.05); and RIF PGE2 by 46%, from 10.5 +/- 1.1 to 5.7 +/- 1.1 pg/min (P < 0.01). Urinary PGE2 was unchanged by ACRIP. Losartan decreased RIF PGE2 by 71%, from 10.8 +/- 0.6 to 3.1 +/- 0.6 pg/min (P < 0.01) but failed to change RIF BK, RIF cGMP, urinary cGMP, or urinary PGE2. These data suggest that the renin-angiotensin system tonically stimulates renal BK production and cGMP formation via a non-AT1 angiotensin receptor and renal PGE2 production via the AT1 receptor.

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