phosphorus-radioisotopes and Cardiomegaly

In spontaneously hypertensive rats (SHR), cardiac adenylate cyclase is desensitized owing to down-regulation of myocardial beta-adrenoceptors and an increase in Gi alpha. We wished to determine whether these biochemical alterations in the beta-adrenoceptor-adenylate cyclase system precede development of hypertensive cardiac hypertrophy or whether this increase occurs only in later stages of the syndrome and represents a secondary phenomenon. Myocardial samples from 5- and 13-week-old SHR and age-matched Wistar Kyoto rats (WKY) as controls were studied. Cardiac beta-adrenoceptors were studied with [125I]cyanopindolol ([125I]ICYP] as radiolabeled ligand. beta-Adrenoceptor subtypes were determined with the beta 1- and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively. Gi alpha proteins were measured with the pertussis toxin-catalysed [32P]ADP ribosylation. Myocardial norepinephrine (NE) content was investigated with high pressure liquid chromatography. In myocardial membranes of 13-week-old SHR, the number of total beta-adrenoceptors as well as beta 1- and beta 2-adrenoceptors was reduced. No difference was observed between SHR and WKY, at age 5 weeks. The nonionic detergent Lubrol PX at 0.5% (vol/vol) increased the amount of detectable Gi alpha by a factor of 14. Under these optimal conditions, Gi alpha was increased by 30% in 13-week-old SHR, but not 5-week-old SHR as compared with WKY. Myocardial NE content was increased by 25-35% in both 5- and 13-week-old SHR as compared with WKY. The results showed that nonspecific beta-adrenoceptor downregulation and an increase in Gi alpha occurs in hypertensive cardiac hypertrophy of SHR. In the prehypertensive stage, these changes were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Diphosphate; Adenylate Cyclase Toxin; Animals; Cardiomegaly; Down-Regulation; GTP-Binding Proteins; Hypertension; Male; Myocardium; Norepinephrine; Pertussis Toxin; Phosphorus Radioisotopes; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Adrenergic, beta; Ribose; Virulence Factors, Bordetella

To determine whether cardiac hypertrophy secondary to chronic renovascular hypertension is associated with altered in vivo myocardial metabolism, phosphorus-31 nuclear magnetic resonance saturation transfer techniques were used to study creatine kinase (CK) kinetics in six chronically hypertensive dogs with moderate cardiac hypertrophy and eight control dogs. The forward rate constant of CK and the flux of phosphocreatine to adenosine triphosphate were determined in both groups of dogs before and during norepinephrine administration (1 microgram/kg per min), used to increase heart rate x systolic blood pressure (rate-pressure product), cardiac output and oxygen consumption. Baseline and norepinephrine-induced changes in rate-pressure product, cardiac output and oxygen consumption were similar in both groups of dogs, as were baseline forward rate constant and flux of phosphocreatine to adenosine triphosphate. However, the norepinephrine-induced changes in forward rate constant and flux were significantly less in hypertensive than in control dogs (p less than 0.05) even though changes in hemodynamic and functional variables were similar in both groups. These data demonstrate that moderate myocardial hypertrophy is associated with altered CK kinetics, which do not appear to affect the heart's ability for global mechanical recruitment at this stage in the hypertensive process. It is possible that the changes in myocardial enzyme kinetics may contribute to diastolic dysfunction previously reported in this model and may be a precursor for ultimate development of heart failure if hypertension is maintained for prolonged periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Animals; Cardiomegaly; Chronic Disease; Creatine Kinase; Disease Models, Animal; Dogs; Echocardiography; Epinephrine; Heart; Hypertension, Renovascular; Kinetics; Magnetic Resonance Spectroscopy; Myocardium; Phosphocreatine; Phosphorus Radioisotopes

Cardiac hypertrophy in adult rabbits was induced by subcutaneous injection of isoproterenol. The rate of [3H]leucine incorporation into acid insoluble material was increased and the extent of [32P]phosphate incorporation into several ribosomal proteins was altered. Specifically, a ribosomal protein with a molecular weight of 32,000 from the 40S ribosomal subunit showed a five-fold increase in phosphate incorporation in the hypertrophic heart whereas a protein with a molecular weight of 28,000 from the 60S subunit showed a four-fold decrease. Phosphorylation of ribosome-associated proteins, which could be removed from ribosomes with 0.72 M KCl, was also changed in the hypertrophic hearts. Six major phosphoproteins (with molecular weights 62,000, 49,000, 36,000, 30,000, 20,000 and 12,000) were detected in both the normal and the hypertrophic hearts. Phosphorylation of the 62 K and the 49 K protein was increased by two- and three-fold, respectively, in the hypertrophic hearts, whereas phosphorylation of the 36 K and the 30 K protein decreased by two-fold. The level of phosphorylation of the 20 K and the 12 K protein was not significantly changed in hypertrophic hearts.

Topics: Animals; Cardiomegaly; Isoproterenol; Kinetics; Leucine; Male; Phosphates; Phosphorus Radioisotopes; Phosphorylation; Rabbits; Ribosomal Proteins; Ribosomes; Tritium

The turnover of cardiac adenine and uracil nucleotides was studied in the hypertrophying rat heart by means of the kinetics of incorporation of labeled phosphate into the alpha-phosphate groups of nucleotides. Cardiac hypertrophy was induced either by chronic isoproterenol treatment (5 mg X kg-1 body wt. daily, s.c.) or by abdominal aortic constriction. In both experimental models, although the labeling of alpha-P groups of adenine nucleotides was at first unmodified, the incorporation of [32P]Phosphate into uracil nucleotides was accelerated early and the stimulation maintained for several days. The intramyocardial concentration of UTP and uracil nucleotides rose during the early phase of hypertrophy, while the ATP and adenine nucleotide pools were depleted. All of these alterations were more pronounced in isoproterenol-treated animals than in those with aortic stenosis. In this experimental model (isoproterenol treatment), the hypertrophy develops faster and is accompanied by a larger increase in cardiac RNA concentration. Thus, the increase in the rate of synthesis of uracil nucleotides may be interpreted as an adaptative change of nucleotide metabolism in response to an increased requirement of precursors for RNA synthesis. The possible limiting role of pyrimidine nucleotides in the hypertrophic process is discussed.

Topics: Adenine Nucleotides; Animals; Cardiomegaly; Female; Phosphorus Radioisotopes; Rats; Rats, Inbred Strains; RNA; Uracil Nucleotides