The effect of chronic administration of beta-guanidinopropionic acid (GPA) on the protein profiling, energy metabolism and right ventricular (RV) function was studied in the rat heart during the weaning and adolescence period. GPA was given in tap water (1-1.5%) using pair drink controls. The feeding of animals with GPA solution for a six week period resulted in elevation of heart to body weight ratio due to body growth retardation. GPA accumulated in the myocardium up to 67.37 +/- 5.3 mumoles.g dry weight and the tissue content of total creatine, phosphocreatine and ATP was significantly decreased to 15%, 9% and 65% of control values respectively. Total activity of creatine kinase (CK) was not changed, but the proportion of mitochondrial (Mi) CK isoenzyme was decreased; the percentage of MB isoenzyme of CK was significantly higher. GPA treatment resulted in an elevation of the content of cardiac collagenous proteins and decrease of non-collagenous proteins in the heart; in parallel, a decrease of the collagen I to collagen III ratio was detected. The function of the RV was assessed using an isolated perfused heart with RV performing pressure-volume work. As compared to pair-drink controls, RV function was significantly impaired the GPA group: at any given right atrial filling pressure, the RV systolic pressure and the rate of pressure development were decreased by almost a factor of two. Elevation of the RV diastolic pressure with increasing pulmonary artery diastolic pressure was also significantly steeper in the GPA group which also showed decrease of cardiac output, especially at high outflow resistance. It may be assumed that chronic administration of GPA deeply influenced metabolic parameters, protein profiles and contractile function of the developing heart. On the other hand, concentrations of glucose, total lipids and triglycerides in blood plasma were not affected. All these data confirm the concept that the CK system is of central importance both for heart function and for the regulation of normal growth of cardiac myocytes.

• MeSH
• Phosphocreatine deficiency   MeSH
• Guanidines pharmacology   MeSH
• Isoenzymes MeSH
• Coronary Circulation MeSH
• Creatine Kinase metabolism   MeSH
• Blood Pressure MeSH
• Rats MeSH
• Myocardium metabolism   MeSH
• Carbon Monoxide metabolism   MeSH
• Rats, Wistar MeSH
• Propionates pharmacology   MeSH
• Sarcoplasmic Reticulum drug effects   metabolism   MeSH
• Heart drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Phosphocreatine MeSH
• guanidinopropionic acid MeSH Browser
• Guanidines MeSH
• Isoenzymes MeSH
• Creatine Kinase MeSH
• Carbon Monoxide MeSH
• Propionates MeSH

Newborn rats were rendered hyperthyroid (daily subcutaneous injections of L-triiodothyronine, 10 micrograms 100 g-1 body weight) or hypothyroid (0.05% 6-n-propyl-2-thiouracil in drinking water to nursing mothers) during the first 3 weeks of postnatal life. Compared with the euthyroid group, hyperthyroidism resulted in: (1) cardiac enlargement with right ventricular preponderance, (2) increased cardiac contractile function, (3) increased Ca2+ uptake by the sarcoplasmic reticulum (SR), (4) decreased sensitivity to the negative inotropic effect of verapamil and (5) greater inhibition of contractile function by ryanodine. Hypothyroidism generally resulted in opposite changes. The data suggest that the development of the heart and its contractile function during early postnatal life depends on the plasma level of thyroid hormones. In particular, the relative contribution of the SR and sarcolemmal Ca2+ transport to the control of cardiac contractility seems to be markedly affected by altered thyroid states. The postnatal maturation of the SR function is accelerated in hyperthyroidism but retarded in hypothyroidism. Consequently, hyperthyroid hearts appear to be less dependent and hypothyroid ones more dependent on trans-sarcolemmal Ca2+ fluxes when compared with age-matched euthyroid animals.

• MeSH
• Thyroid Hormones physiology   MeSH
• Rats, Inbred Strains MeSH
• Myocardial Contraction drug effects   physiology   MeSH
• Rats MeSH
• Myocardium metabolism   MeSH
• Animals, Newborn MeSH
• Ryanodine pharmacology   MeSH
• Sarcoplasmic Reticulum metabolism   MeSH
• Thyroid Gland physiology   MeSH
• Body Weight MeSH
• Calcium metabolism   MeSH
• Verapamil pharmacology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Thyroid Hormones MeSH
• Ryanodine MeSH
• Calcium MeSH
• Verapamil MeSH

The function of the hypertrophic right ventricle (RV) was studied in adult rats with hypoxic pulmonary hypertension induced by intermittent high-altitude (IHA) exposure. The isolated RV working heart preparation that was employed enabled us to estimate ventricular contractile and pump performance under controlled loading conditions. In rats exposed to IHA hypoxia the elevated RV systolic pressure and maximum rate of pressure development were observed at various levels of preload or afterload. The peak indices of mechanical performance were almost doubled in these animals when compared with the normoxic group, while the index of contractility remained unchanged. Maximum ventricular performance was found to be a linear function of the relative RV weight. No evidence of RV pump dysfunction was detected in rats exposed to IHA; moreover, the ability of the ventricle to maintain cardiac output against increased pulmonary resistance was markedly improved. The prevention of tricuspid regurgitation by using an artificial valve did not influence the functional curves and the peak ventricular performance. The regression of hypertrophy was accompanied by a reversal of ventricular function to control values, except for the persisting slight increase of peak RV pressure. It may be concluded that the increase of the RV mass in IHA-exposed rats serves to improve maximum ventricular performance, which aids in overcoming and elevated pulmonary resistance without disturbing the pump function.

• MeSH
• Rats, Inbred Strains MeSH
• Cardiomegaly physiopathology   MeSH
• Blood Pressure MeSH
• Rats MeSH
• Hypertension, Pulmonary complications   physiopathology   MeSH
• Regression Analysis MeSH
• Body Weight MeSH
• Organ Size MeSH
• Altitude Sickness complications   physiopathology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH