Rise and Fall of Agonist-Evoked Platelet Ca in Hypertensive Rats

We previously reported an enhanced peak response of intracellular free Ca to thrombin in platelets of spontaneously hypertensive rats in comparison with normotensive Wistar-Kyoto rats. In the present study, we compared the platelet intracellular Ca response to the receptor-linked agonist thrombin with the response to the Ca ionophore ionomycin. Basal intracellular Ca was higher in hypertensive platelets as was leakage of fura-2. We confirmed the previous finding that the thrombin-induced intracellular Ca peak is greater in platelets of hypertensive rats and noted that the rate of recovery from peak intracellular Ca is significantly greater in this model. In contrast, the peak platelet intracellular Ca response to ionomycin (50 nM and 5 /uM) was not different between the two strains, and the rate of recovery from the peak response was only slightly depressed in hypertensive rats after the low dose of ionomycin. Internal Ca discharge capacity, assessed by the intracellular Ca response to a maximal dose of ionomycin in Ca-free medium, was not different between platelets of the two strains. Thus, activated platelet intracellular Ca is not altered in the hypertensive rat when the nonphysiological ionophore ionomycin is used as agonist. However, a heightened intracellular Ca response is observed when the receptor-mediated agonist thrombin is used. These results are consistent with the hypothesis that differences in receptor-linked second messenger pathways underlie the altered intracellular Ca response in platelets of genetically hypertensive rats and may contribute to differences both in the mobilization of Ca and in its fall. {Hypertension 1991;18:758-762)