Effects of losartan, an angiotensin II antagonist, on the development of cardiac hypertrophy due to volume overload. 1995

M Ishiye, and K Umemura, and T Uematsu, and M Nakashima
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.

To investigate the contribution of a cardiac renin-angiotensin system to cardiac hypertrophy due to volume overload, the effects of losartan, a non-peptide angiotensin (Ang) II type 1 (AT1) receptor antagonist on left ventricular hypertrophy (LVH) was studied. LVH was produced in male Wistar rats by volume overload secondary to aortic insufficiency (AI). Losartan (10 mg/kg/d) was orally administered for 2 weeks after surgery to both AI and sham-operated (control) rats. Two weeks after surgery, aortic pulse pressure and left ventricular (LV) weight were markedly increased in the AI rats as compared with the control group, whereas cardiac angiotensin converting enzyme (ACE) activity remained unchanged. The effects of the chronic administration of losartan an AT1 receptors were verified by the blockade of Ang II pressor response. Losartan treatment produced a significant reduction in LVH in AI rats without affecting the systolic blood pressure. In separate groups of rats, to elucidate the mechanisms of the attenuation of LVH by treatment with losartan, we determined plasma and LV immunoreactive Ang II content and plasma renin activity (PRA). LV Ang II content increased in AI rats, while plasma Ang II content, PRA and II concentration were increased by the treatment. There was a significant positive correlation between LV weight and LV Ang II content. These results suggest that cardiac Ang II, rather than circulating Ang II, plays an important role in the LVH due to volume overload via the AT1 receptor.

UI MeSH Term Description Entries
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D007703 Peptidyl-Dipeptidase A A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of ANGIOTENSIN I to ANGIOTENSIN II, with increase in vasoconstrictor activity, but no action on angiotensin II. It is also able to inactivate BRADYKININ, a potent vasodilator; and has a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. (From https://www.uniprot.org April 15, 2020). ACE1 Angiotensin-Converting Enzyme 1,ACE1 Protein,Angiotensin Converting Enzyme,Angiotensin Converting Enzyme 1,Antigens, CD143,CD143 Antigens,Dipeptidyl Carboxypeptidase I,Kininase II,Peptidase P,Angiotensin I-Converting Enzyme,Carboxycathepsin,Dipeptidyl Peptidase A,Kininase A,ACE1 Angiotensin Converting Enzyme 1,Angiotensin I Converting Enzyme,Carboxypeptidase I, Dipeptidyl,Peptidyl Dipeptidase A
D008297 Male Males
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D012083 Renin A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19. Angiotensin-Forming Enzyme,Angiotensinogenase,Big Renin,Cryorenin,Inactive Renin,Pre-Prorenin,Preprorenin,Prorenin,Angiotensin Forming Enzyme,Pre Prorenin,Renin, Big,Renin, Inactive
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002306 Cardiac Volume The volume of the HEART, usually relating to the volume of BLOOD contained within it at various periods of the cardiac cycle. The amount of blood ejected from a ventricle at each beat is STROKE VOLUME. Heart Volume,Cardiac Volumes,Heart Volumes,Volume, Cardiac,Volume, Heart,Volumes, Cardiac,Volumes, Heart
D006332 Cardiomegaly Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES. Cardiac Hypertrophy,Enlarged Heart,Heart Hypertrophy,Heart Enlargement,Cardiac Hypertrophies,Enlargement, Heart,Heart Hypertrophies,Heart, Enlarged,Hypertrophies, Cardiac,Hypertrophies, Heart,Hypertrophy, Cardiac,Hypertrophy, Heart
D000804 Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS. Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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