Biomaterial Database

Selective increase in endothelin-1 and endothelin A receptor subtype in the hypertrophied myocardium of the aorto-venacaval fistula rat. 1995

L A Brown, and D J Nunez, and C I Brookes, and M R Wilkins

Department of Clinical Pharmacology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.

OBJECTIVE At present little is known about the factors that regulate the expression of the endothelins and their receptors in cardiac tissue in vivo. The aim of this study was to investigate changes in expression of the endothelins (ET-1, ET-2, and ET-3) and their receptors (ETAR and ETBR) in the hypertrophied heart of the aortovenocaval (AV) fistula rat. METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify cardiac mRNA expression of the endothelins and their receptors during the development of cardiac hypertrophy, while radioligand binding was employed to quantify the amount of [125I]-ET-1 binding to cardiac membranes. Tissue and plasma concentrations of ET-1 were measured by radioimmunoassay. RESULTS In control sham operated animals, ET-1 mRNA was approximately fivefold greater in atria than in ventricles (P < 0.05), but there were no atrioventricular differences in ET-2 or ET-3 mRNA. In the AV fistula rats there was a prompt three- to fourfold increase in ET-1 mRNA in atria and a progressive five- to sevenfold rise in ventricles during cardiac hypertrophy. There were no changes in ET-2 or ET-3 transcript prevalences, except for a late rise (35 d) in ET-2 mRNA levels in left ventricle. Consistent with ET-1 mRNA measurements, immunoreactive endothelin levels were increased by 7 d in atria, but not in ventricles. In control rat hearts, ETAR mRNA levels were similar in atria and ventricles, but the prevalence of ETBR was approximately sevenfold greater in the former. ETAR mRNA prevalence increased with hypertrophy in all chambers, while ETBR transcript levels were raised only in the right ventricle. There was no significant difference in [125I]-ET-1 binding between atrial samples from 35 d control and 35 d AV fistula rats, suggesting rapid turnover of endothelin receptors balanced by increased transcription from the ETAR gene. CONCLUSIONS During cardiac hypertrophy in AV fistula rats there is increased activity of the endothelin system mediated principally by ET-1 and the ETAR subtype.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
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
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
D001483	Base Sequence	The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.	DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D016133	Polymerase Chain Reaction	In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.	Anchored PCR,Inverse PCR,Nested PCR,PCR,Anchored Polymerase Chain Reaction,Inverse Polymerase Chain Reaction,Nested Polymerase Chain Reaction,PCR, Anchored,PCR, Inverse,PCR, Nested,Polymerase Chain Reactions,Reaction, Polymerase Chain,Reactions, Polymerase Chain
D016232	Endothelins	21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides.	Endothelium-Derived Vasoconstrictor Factors,Endothelin,Vasoconstrictor Factors, Endothelium-Derived
D017208	Rats, Wistar	A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.	Wistar Rat,Rat, Wistar,Wistar Rats