>Clopidogrel Rescues the Adverse Cerebral Vascular Effects Associated with Angiotensin II-Induced Hypertension.

Hypertension is a common risk factor for thrombotic diseases like heart attack and stroke. Chronic high blood pressure causes endothelial dysfunction which accelerates the atherosclerotic process resulting in plaque instability. Since hypertensive patients have an increased risk of thrombotic diseases, many are prescribed the antiplatelet drug, clopidogrel. The present study sought to determine clopidogrel's effect on blood pressure, cerebral blood flow, and vascular remodeling in angiotensin II (Ang II)-induced hypertensive mice. Previous results from our laboratory demonstrated that clopidogrel attenuated P2Y -induced vasoconstriction in cerebral arteries which could result in an increase in downstream cerebral blood flow. Therefore, we hypothesized that clopidogrel increases cerebral blood flow and decreases vascular remodeling in Ang II-induced hypertensive mice. Ang II infusion pump implantation or sham surgeries were performed in 48 C57BL/6 mice at 16-18 weeks of age. Ang II was infused continuously at a rate of 800ng/kg/min for 4 weeks. The mice were also administered vehicle or clopidogrel (10mg/kg/day) starting the day after surgery. Data are presented as means ± SEM, n = 8-12 mice/group. Ang II significantly reduced blood flow, and clopidogrel-treated mice had blood flow that was not different from either the sham or Ang II mice (sham vehicle: 305.6 ± 16.17; sham clopidogrel: 313.0 ± 15.27; Ang II vehicle: 244.1 ± 12.76; Ang II clopidogrel: 267.6 ± 14.96). Posterior cerebral arteries were harvested from animals at the end of the experiment. The outer and lumen diameters were reduced in the vessels in Ang II treated mice. However, clopidogrel treatment did not modify this vascular remodeling in the Ang II treated mice. The results suggest that clopidogrel demonstrates protective potential in hypertensive mice. Further studies are required to determine the long-term effects of clopidogrel on hypertension associated vascular remodeling.