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. The purpose of the persent proposal is to test the hypothesis that genetic or pharmacological factors that decrease ACE activity favorably alter cardiovascular morbidity and mortality by enhancing the effect of brandykinin on fibrinolytic balance.
SPECIFIC AIMS : Test the hypothesis that methacholine and brandykinin-stimulated t-PA release is impaired in patients with risk factors fro coronary artery disease: (a) patients with hypertension versus normal controls, (b) smokers versus non-smoking normal controls, and (c) patients with hyperlipidemia versus normal controls. Test the hypothesis that ACE inhibitors improve basal and stimulated t-PA release in patients with hypertension through effects on brandykinin. Test the hypothesis that genetic polymorphisms in the ACE and t-PA genes influence endothelial t-PA release.
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