title: Effect of amlodipine and cilazapril treatment on platelet Ca2+ handling in spontaneously hypertensive rats.
abstract: Abnormal Ca2+ handling and enhanced aggregation response have been reported in platelets from spontaneously hypertensive rats (SHR) and patients with essential hypertension, and thought to be involved in the progression of target organ damage of hypertension. It is important to examine whether antihypertensive therapy can improve the abnormal platelet response in hypertension. We investigated the effect of antihypertensive treatment such as amlodipine and cilazapril on Ca2+ handling and aggregation response in SHR platelets. Four-week-old male SHR were divided into three groups. Each group was treated with amiodipine (A: 10 mg/kg/day), cilazapril (C: 10 mg/kg/day) or vehicle (V) for 8 weeks by gavage. At 12-week-old, platelet [Ca2+]i was measured with fura-2 in each group of SHR and age-matched Wistar-Kyoto rats (WKY) as normal control. Systolic blood pressure in amlodipine and cilazapril treated groups were similar with WKY and significantly lower than vehicle treated group (A: 124 +/- 9, C: 126 +/- 9, WKY: 122 +/- 10 and V: 180 +/- 9 mmHg, respectively). The basal [Ca2+]i in the three groups of SHR were similar and higher than WKY (A: 47 +/- 1.7, C: 47 +/- 1.2, V: 48 +/- 3.9 and WKY: 40 +/- 4.0 nmol/l, respectively). There were no significant differences in thrombin (0.1 U/ml)-stimulated [Ca2+]i rise in the presence or absence of extracellular Ca2+ among the three groups of SHR and these were higher than WKY. Intracellular Ca2+ discharge capacity, assessed by the ionomycinstimulation was similar in the all groups. Thrombin-induced maximum platelet aggregation responses in the three groups of SHR were similar and higher than WKY. The antihypertensive treatment of Ca2+ antagonist or ACE inhibitor gave no change in intraplatelet Ca2+ metabolism in SHR. These results support the hypothesis that an abnormal Ca2+ handling in SHR platelet is genetically determined and not improved by hypotensive therapy.
authors.affiliation: Department of Clinical Laboratory of Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. teto@hiroshima-u.ac.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oshima
authors.forename: Norihisa
authors.initials: N
authors.lastname: Ono
authors.forename: Ryoji
authors.initials: R
authors.lastname: Ozono
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
authors.forename: Mari
authors.initials: M
authors.lastname: Ishida
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ishida
authors.forename: Narimasa
authors.initials: N
authors.lastname: Miho
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Nakashima
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yano
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kambe
mesh_terms: D017311:Amlodipine / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000097:blood*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D017315:Cilazapril / Q000627:therapeutic use*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D015759:Ionomycin; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013917:Thrombin / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D017315:Cilazapril; D017311:Amlodipine; D015759:Ionomycin; D013917:Thrombin; D002118:Calcium