Salt sensitivity affects a fraction of hypertensive and normotensive subjects, but biochemical markers that target salt-sensitive individuals are not available at present. The aim of these studies was to establish if calmodulin-phosphodiesterase (CaM-PDE) activator (J Clin Invest 82: 276, 1988) and platelet cyclic nucleotides could serve as potential markers of salt sensitivity. The results demonstrated that CaM-PDE activator was increased in the heart of Dahl salt-sensitive rats (DS/JR) compared to Dahl salt-resistant (DR/JR) animals fed a 1% sodium diet. Normotensive male Wistar rats given a low (0.15%) or high (3.5%) sodium diet from age 7 weeks to 11 weeks presented significant increases (p less than 0.01) of three parameters: blood pressure (from 106 +/- 4 to 128 +/- 8 mmHg); platelet aggregation in response to ADP and thrombin; and CaM-PDE activator levels (from 1.57 +/- 0.14 to 2.8 +/- 0.18). Basal as well as stimulated cyclic nucleotide levels were significantly reduced in rats fed the high sodium diet. Since the degree of stimulation by the agonists was unaltered, the results are compatible with augmented PDE activity. These preliminary data suggest that CaM-PDE activator should be explored as a potential marker of salt sensitivity.