title: Cardiac adenylyl cyclase, beta-adrenergic receptors, and G proteins in salt-sensitive hypertension.
abstract: The present study investigated whether high salt intake (8%) in Dahl salt-sensitive and salt-resistant rats with and without hypertension produces a heterologous desensitization of cardiac adenylyl cyclase as observed in various types of hypertension and human heart failure. In membranes from Dahl salt-sensitive rats on a high-salt diet (8%) basal, isoproterenol-, 5'-guanylylimidodiphosphate-, and forskolin-stimulated adenylyl cyclase was reduced compared with the low-salt (0.4%) group and Dahl salt-resistant rats on either 0.4% or 8% sodium chloride. The activity of the catalyst was depressed, and the expression of the immunodetectable inhibitory G proteins Gi alpha was increased in Dahl salt-sensitive rats on 8% sodium chloride, whereas the density of beta-adrenergic receptors and the activity of the stimulatory G protein Gs alpha reconstituted into Gs alpha-deficient S49 cyc- mouse lymphoma cell membranes were unchanged in any condition studied. We conclude that high salt intake in salt-sensitive hypertensive Dahl rats produces hypertension, cardiac hypertrophy, and heterologous desensitization of cardiac adenylyl cyclase. The latter alteration is due to an increase of Gi alpha proteins and a depressed catalyst activity of adenylyl cyclase. The results demonstrate that heterologous adenylyl cyclase desensitization can precede the development of contractile dysfunction in later stages and can occur independently of changes in beta-adrenergic receptors.
authors.affiliation: Medizinische Klinik I, Universität München, Klinikum Grosshadern, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Böhm
authors.forename: P
authors.initials: P
authors.lastname: Gierschik
authors.forename: A
authors.initials: A
authors.lastname: Knorr
authors.forename: U
authors.initials: U
authors.lastname: Schmidt
authors.forename: K
authors.initials: K
authors.lastname: Weismann
authors.forename: E
authors.initials: E
authors.lastname: Erdmann
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced / Q000503:physiopathology*; D002462:Cell Membrane / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D007106:Immune Sera; D007700:Kinetics; D008223:Lymphoma; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D011863:Radioimmunoassay; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012965:Sodium Chloride / Q000633:toxicity; D015293:Transducin / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D007106:Immune Sera; D009842:Oligopeptides; D011943:Receptors, Adrenergic, beta; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D009243:NAD; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; D006165:Guanylyl Imidodiphosphate; D012965:Sodium Chloride; D019204:GTP-Binding Proteins; D015293:Transducin; D000262:Adenylyl Cyclases