PLATELET INVOLVEMENT IN REFLEX CUTANEOUS VASODILATION

血小板参与反射性皮肤血管舒张

• 批准号: 7951342
• 负责人: LACY HOLOWATZ
• 金额: $ 2.91万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951342
• 关键词: Aging; Aspirin; Attenuated; Blood Platelets; Blood Vessels; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Coupled; Crossover Design; Cutaneous; Data; Disease; Dose; Double-Blind Method; Enzymes; Fever; Funding; Grant; Heat Stress Disorders; Heating; Human; Institution; Laser-Doppler Flowmetry; Measures; Mediating; Microdialysis; Nitric Oxide; Nitric Oxide Synthase; Oral; Pathway interactions; Pharmaceutical Preparations; Platelet Activation; Platelet Inhibitors; Plavix; Prevention therapy; Procedures; Protein Isoforms; Reflex action; Research; Research Personnel; Resources; Role; Screening procedure; Site; Skin; Source; Testing; Tissues; United States National Institutes of Health; Vasodilation; Vasodilator Agents; clopidogrel; middle age; systemic intervention

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human aging is associated with attenuated cutaneous vasodilation (VD) during hyperthermia due to a reduction in non-nitric oxide (NO)- and NO-dependent mechanisms. Preliminary data suggest that standard aspirin therapy for prevention of atherothrombotic disease severely attenuates reflex cutaneous vasodilation in middle-aged human skin (58¿3 years). Aspirin therapy may inhibit COX isoforms in platelets and vascular tissue, thus blocking a key enzyme involved in VD. Alternatively, platelet activation during heat stress may release substances mediating pathways contributing to VD. We will examine the roles of platelets and vascular COX on reflex VD using systemic interventions (low-dose aspirin and/or platelet inhibitor, clopidogril bisulfate) coupled with a localized examination of NOS- and COX-derived vasodilators. Hypothesis 1: Low-dose aspirin (81 mg) will attenuate reflex cutaneous vasodilation through COX-dependent mechanisms. Hypothesis 2: Specific platelet inhibition with clopidogrel bisulfate will not attenuate reflex cutaneous vasodilation. After screening subjects undergo baseline testing (no oral pharmacologics) incorporating cutaneous microdialysis (MD), whole body heating, and laser Doppler flowmetry. For the testing procedure, four intradermal microdialysis probes will be placed in the skin. Microdialysis sites are assigned drug treatments to serve as to serve as Control, nitric oxide synthase-inhibited (NOS-I), COX-inhibited (COX-I) and NOS and COX inhibited (NOS-I+COX-I). Then subjects enter the double-blind crossover design study with 81 mg of aspirin and/or 75 mg of clopidogrel bisulfate (Plavix ¿). Subjects take each drug for 7 days followed by a 2 week washout before the start of the other drug. Analyses include three-way repeated measures ANOVA. PROC MIXED procedure in SAS.

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