In most tissues stimulation of the phosphatidylinositol turnover pathway causes release of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], which is subsequently metabolized to a wide range of inositol phosphate isomers deriving from both phosphorylation and dephosphorylation reactions. However, addition of noradrenaline to isolated intact neonatal-rat hearts generated only those inositol phosphates produced by dephosphorylation of Ins(1,4,5)P3. Products of the InsP3 kinase pathway were absent from the profiles, except after prolonged stimulation. In contrast, addition of noradrenaline to isolated cultured neonatal-rat cardiomyocytes caused the release of Ins(1,4,5)P3, which was metabolized by both phosphorylation and dephosphorylation pathways to yield a complex range of inositol phosphate isomers, as observed in many other cell types. These differences between the responses in intact tissues and in isolated cell preparations were not caused by the different conditions used for [3H]inositol labelling. Furthermore, results could not be explained by overgrowth of other cell types in the isolated cell preparations. Thus the results demonstrate that the isolation and culture of rat neonatal cardiomyocytes produces alterations in the nature of the phosphatidylinositol turnover pathway.

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Sodium homeostasis exerts a powerful influence on the cardiovascular system in normotensive and hypertensive animals. Previous studies indicate that factors other than blood pressure can influence cardiac hypertrophy. In the present experiments, we evaluated the effects of different sodium diets in the two-kidney, one clip hypertension model in the rat. After the renal artery had been cupped, the rats received a normal sodium (177 meq/kg), high sodium (517 meq/kg), and low sodium (7 meq/kg) diet during 4 weeks. The final blood pressure was almost the same in the three groups (normal sodium 170 ±12 mm Hg; low sodium 168 ±4 mm Hg; and high sodium 162 ±7 mm Hg). Sodium restriction significantly reduced the development of cardiac hypertrophy as compared with rats on normal or high sodium diets. Thus, ventricular weight and ventricular weight/body weight ratio were significantly higher in rats subjected to a normal or high sodium diet (p<0.01). The hypertrophied hearts of rats on normal and high sodium diets showed a larger increase in the number of cardiac ^-adrenergk receptors than those observed in hearts from low sodium diet, clipped rats. These results show that sodium modulates the development of cardiac hypertrophy in two-kidney, one clip hypertensive rats. Similarly, the cardiac /3-adrenergic receptors appear to be influenced by dietary sodium intake. A possible role of the sympathetic nervous system is suggested. (Hypertension 1990;15(suppl I):I-157-I-160)

1. The effect of endothelin on phosphatidylinositol turnover in rat atria was investigated by measuring the generation of inositol phosphates following [3H]-inositol labelling. 2. In the presence of 10 mmol/L LiCl, endothelin caused dose-dependent increases in the accumulation of inositol mono, bis and trisphosphates which were maximal at 10(-6) mol/L endothelin. The dose-response relationship was similar in right and left atria, but right atria showed a higher maximal inositol phosphate response. 3. Endothelin produced a rapid and transient stimulation of inositol trisphosphate accumulation, which peaked at 15 s followed by a slower increase which continued linearly past 20 min. 4. The time course of inositol trisphosphate release under noradrenaline stimulation showed a similar profile but the maximum stimulation was smaller than endothelin. 5. As with endothelin, responses to noradrenaline also were higher in right atria compared with left atria. 6. These data demonstrate that endothelin receptors in rat atria are coupled to the stimulation of the phosphatidylinositol turnover pathway in an essentially similar manner to alpha 1-adrenoceptors. The phosphatidylinositol pathway may be important in mediating the reported cardiac actions of endothelin.

1. Cultured neonatal myocytes are commonly used as a model system for the study of cardiac phosphatidylinositol (PI) turnover. 2. In neonatal myocytes stimulation with noradrenaline causes the release of the Ca2(+)-releasing compound inositol-1,4,5-trisphosphate and the generation of the Ca2(+)-regulatory compound inositol-1,3,4,5-tetrakisphosphate. 3. Addition of noradrenaline to intact, neonatal rat hearts stimulates the release of inositol-1,4,5-trisphosphate, but not inositol-1,3,4,5-tetrakisphosphate. 4. These findings show that the isolation and culture of the neonatal myocyte causes changes in the PI turnover pathway so that it becomes similar to that described in other cell types and different from that in intact myocardial tissue. 5. The neonatal myocyte is not a useful model for the study of cardiac PI turnover.