The P2Y12 receptor antagonist clopidogrel blocks platelet aggregation, improves systemic endothelial nitric oxide bioavailability, and has anti-inflammatory effects. Since P2Y12 receptors have been identified in the vasculature, we hypothesized that clopidogrel ameliorates angiotensin II (Ang II) -induced vascular functional changes by blockade of P2Y12 receptors in the vasculature. Male Sprague Dawley rats were infused with Ang II (60 ng.min-1) or vehicle for 14 days. The animals were treated with clopidogrel (10mg•kg-1•day-1) or vehicle. Vascular reactivity was evaluated in second-order mesenteric arteries. Clopidogrel treatment did not change systolic blood pressure [(mmHg) control-vehicle, 117±7.1 vs. control- Clopidogrel, 125±4.2; AngII-vehicle, 197±10.7 vs. AngII-Clopidogrel, 198±5.2], but it normalized increased phenylephrine-induced vascular contractions [(%KCl) vehicle-treated, 182.2±18 vs. Clopidogrel, 133±14%), as well as impaired vasodilation to acetylcholine [(%) vehicle-treated, 71.7±2.2 vs. Clopidogrel, 85.3±2.8) in Ang II-treated animals. Vascular expression of P2Y12 receptor was determined by western blot. Pharmacological characterization of vascular P2Y12 was performed with the P2Y12 agonist 2-MeS-ADP. Although 2-MeSADP induced endothelium-dependent relaxation [(Emax %) = 71%±12), as well as contractile vascular responses (Emax %= 83±12) these actions are not mediated by P2Y12 receptor activation. 2-MeS-ADP produced similar vascular responses in control and Ang II rats. These results indicate potential effects of Clopidogrel, such as improvement of hypertension-related vascular functional changes that are not associated with direct actions of clopidogrel in the vasculature, supporting the concept that activated platelets contribute to endothelial dysfunction, possibly via impaired NO bioavailability.
Tags: sprague-dawley, sub, the-vasculature, vasculature
Related posts:
- Obesity is the major contributor to vascular dysfunction and inflammation in high fat diet hypertensive rats
- Clopidogrel application: beyond coronary artery disease
- Fenofibrate improves endothelial function in the brachial artery and forearm resistance arterioles of statin-treated type 2 diabetic patients
- Countervailing vascular effects of rosiglitazone in high cardiovascular risk mice: Role of oxidative stress and PRMT-1
- Relation of circulating progenitor cells to vascular function and oxidative stress with long term training and short term detraining in older men
Related posts brought to you by Yet Another Related Posts Plugin.
