Renin-angiotensin system inhibition improves coronary flow reserve in hypertension.
Angiotensin II not only elevates arterial pressure, it adversely alters hemodynamics and cardiovascular structure and exacerbates the course of hypertensive disease. Alterations in coronary hemodynamics, including reductions in coronary blood flow and flow reserve, reflect the pathophysiology of arteriolar disease and associated endothelial dysfunction thereby promoting coronary insufficiency and increasing overall cardiovascular risk. In spontaneously hypertensive rats, coronary flow reserve, the difference between basal coronary blood flow and the flow achieved during maximal coronary vasodilation achieved by physiological or pharmacological interventions, is drastically impaired at rest; however, it can be improved significantly by pharmacological agents that inhibit the renin-angiotensin system, alone or in combination. The combination of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin-II (type 1) receptor blocker, in equidepressor doses, markedly improved coronary flow reserve to levels seen in normotensive Wistar Kyoto rats after 12 weeks of treatment, while diminishing cardiovascular mass and improving systemic hemodynamics and ventricular metabolic demands. These findings suggest the potential merits for clinical studies employing the combination of ACE inhibitor and angiotensin receptor blocker therapy in patients with hypertension and hypertensive heart disease.
Frohlich
E D
ED
Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121, USA.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors