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.

Disparate effects of eplerenone, amlodipine and telmisartan on podocyte injury in aldosterone-infused rats

“…The dose of aldosterone administered was 1.5 μg/h which was determined in a pilot experiment. After recovery from surgery, animals were randomized to receive one of the following 28-day treatments: vehicle (control rats, CR); aldosterone (ARR); aldosterone + eplerenone [23] (100 mg/kg/day, Pfizer, USA) (A/ERR); aldosterone + telmisartan [24] (3 mg/kg/day, Boehringer Ingelheim, Germany) (A/TRR); and aldosterone + amlodipine [25,26] (10 mg/kg/day, Pfizer) (A/ARR) (n = 6 rats/group). The daily dose of reagents was dissolved in 60% acetonitrile (Sigma, St Louis, MO, USA) and diluted in distilled water before gavage.…”