The vascular biology of hypertension and atherosclerosis and intervention with calcium antagonists and angiotensin-converting enzyme inhibitors

Recent advances in the understanding of vascular disease genesis suggest th at atherosclerosis and hypertension, primary targets of therapy in the INte rnational VErapamil SR/trandolapril STudy (INVEST), are closely related. A unified model for the development of cardiovascular disease (CVD) is emergi ng from recent advances related to atherosclerosis and hypertension. The pr ocess of vascular disease appears to begin early in life, when signs of end othelial dysfunction first appear. A primary cause of CVD progression is in creased oxidative stress in the endothelium caused by multiple risk factor conditions, including heredity, dyslipidemia, smoking, diabetes, and elevat ed systolic blood pressure (SBP > 110 mmHg). The renin-angiotensin and kall ikrein-kinin systems are important regulators of blood pressure and atheros clerosis. In the renin-angiotensin system, angiotensin-converting enzyme (A CE) mediates generation of angiotensin II (ang II) at local vascular sites and in the plasma and also degrades bradykinin. Information derived from IN EST will help to identify treatment strategies, such as those containing a calcium antagonist and an ACE inhibitor, that are targeted directly at the vascular disorder responsible for hypertension and atherosclerosis.