Rise and fall of agonist-evoked platelet Ca2+ in hypertensive rats.
We previously reported an enhanced peak response of intracellular free Ca2+ to thrombin in platelets of spontaneously hypertensive rats in comparison with normotensive Wistar-Kyoto rats. In the present study, we compared the platelet intracellular Ca2+ response to the receptor-linked agonist thrombin with the response to the Ca2+ ionophore ionomycin. Basal intracellular Ca2+ was higher in hypertensive platelets as was leakage of fura-2. We confirmed the previous finding that the thrombin-induced intracellular Ca2+ peak is greater in platelets of hypertensive rats and noted that the rate of recovery from peak intracellular Ca2+ is significantly greater in this model. In contrast, the peak platelet intracellular Ca2+ response to ionomycin (50 nM and 5 microM) 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 Ca2+ discharge capacity, assessed by the intracellular Ca2+ response to a maximal dose of ionomycin in Ca(2+)-free medium, was not different between platelets of the two strains. Thus, activated platelet intracellular Ca2+ is not altered in the hypertensive rat when the nonphysiological ionophore ionomycin is used as agonist. However, a heightened intracellular Ca2+ 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 Ca2+ response in platelets of genetically hypertensive rats and may contribute to differences both in the mobilization of Ca2+ and in its fall.
Oshima
T
T
Division of Nephrology and Hypertension, Oregon Health Sciences University, Portland.
Young
E W
EW
Bukoski
R D
RD
McCarron
D A
DA
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology
D015759:Ionomycin; D013917:Thrombin; D002118:Calcium