HYPERCHOLESTEROLEMIA MODULATES THE EFFECTS OF NITRENDIPINE ON BLOOD-PRESSURE AND PLATELET-FUNCTION IN ESSENTIAL-HYPERTENSION

Both marked hypercholesterolemia and severe hypertension have been reported to be associated with an enhanced sensitivity of blood platelets to activating agents. To investigate a possible mutual synergistic effect of moderate hypercholesterolemia and mild hypertension on platelet reactivity, we studied in 29 patients the response to aggregating agents, ADP and collagen, and the intracellular cyclic AMP content and cytosolic Ca2+ concentration that participate, respectively, as inhibitory and stimulatory mediators in platelet responses. When compared to age- and blood pressure-matched patients with normal or slightly elevated plasma cholesterol, the patients with total platelet cholesterol higher than 6.4 mM were characterized by a decreased response to collagen and ADP (14.5 +/- 3.0 vs. 23.8 +/- 2.0 a.u. and 17.7 +/- 4.5 vs. 26.9 +/- 2.7 a.u., respectively), a tendency to a reduced cAMP content both in the basal state and after phospho-diesterase inhibition by Ro-15 2041 (2.83 +/- 0.18 vs. 3.26 +/- 0.22-mu-mol/10(8) cells and 4.57 +/- 0.29 vs. 5.38 +/- 0.36-mu-mol/10(8) cells, respectively), and no change in cytosolic Ca2+ concentration (190 +/- 11 vs. 203 +/- 13 nM). After a chronic treatment with nitrendipine (20 mg/day for 6 months), blood pressure, platelet [Ca2+]i and cAMP content decreased in the patients with normal or moderately elevated hypercholesterolemia (p < 0.001, < 0.001, and < 0.05, respectively), but these effects were attenuated or absent in the patients with higher hypercholesterolemia. Plasma lipids and the platelet-aggregating response to ADP and collagen were unchanged by this long-term nitrendipine treatment in both groups. These data indicate that hypercholesterolemia can modulate the antihypertensive effect of nitrendipine and its effects on platelet parameters.