PMID: 9191503Oct 1, 1996Paper

Responses of heart function and intracellular free Ca2+ to phosphatidic acid in chronic diabetes

The Canadian Journal of Cardiology
Y J XuNaranjan S Dhalla

Abstract

In view of the crucial role of phosphatidic acid (PA) in signal transduction and Ca(2+)-handling in myocardium, it was the objective of this study to examine the effects of PA on cardiac contractile force and intracellular free Ca2+ in control and chronic diabetic rats. Diabetes was induced in rats by a single intravenous injection of streptozotocin (65 mg/kg.) and the animals were used for experiments eight weeks after the injection. Heart function was measured by using the isolated perfused heart preparations, and values for systolic pressure, diastolic pressure, rate of contraction (+dP/dt) and rate of relaxation (-dP/dt) were monitored. Intracellular free Ca2+ in cardiomyocytes was estimated by employing Fura-2/AM method. PA (5 x 10(-8) to 1 x 10(-5) M) produced a concentration-dependent increase in +dP/dt and -dP/dt in the isolated heart; however, these responses were significantly attenuated in diabetic hearts. ATP also caused a positive inotropic effect at concentrations of 1 x 10(-5) to 1 x 10(-4) M but the magnitude of these responses was similar in both control and diabetic groups. Using freshly isolated cardiomyocytes and Fura-2 technique, PA (1 x 10(-6) to 1 x 10(-4) M) was observed to evoke a concentration-dependen...Continue Reading

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