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The renin-angiotensin system is involved in the regulation of blood pressure and electrolyte balance. Angiotensinogen, a globulin formed in the liver, is converted to angiotensin I by renin, an enzyme produced by the juxtaglomerular cells of renal afferent arterioles. Renin release can be triggered by a drop in systemic blood pressure (either directly through baroreceptors or indirectly through reduction in renal tubular fluid, as in hypotension or dehydration) or in serum sodium chloride concentration. Angiotensin I is converted by the ACE, a glycoprotein produced chiefly in the lung, to angiotensin II. (ACE also degrades bradykinin, a vasodilator.) Angiotensin II is a potent vasoconstrictor and neurotransmitter, which raises peripheral vascular resistance and induces sodium retention by stimulating the adrenal cortex to secrete aldosterone. In addition, angiotensin II stimulates cell migration and the growth and proliferation of vascular smooth muscle. Because it plays a pivotal role in the pathogenesis of essential hypertension, congestive heart failure, and diabetic nephropathy, drugs that block production of angiotensin II are useful in those disorders. ACE inhibitors have an established place in the treatment of essential hypertension, congestive heart failure, and left ventricular dysfunction after myocardial infarction. Their effectiveness in hypertension is less marked in black patients than in nonblacks. ACE inhibitors may lessen cardiovascular risk by improving endothelial dysfunction, reducing inflammation, and promoting fibrinolysis by inhibiting plasminogen activator inhibitor-1. The protection afforded by these agents against vascular complications of DM is independent of their effect on blood pressure. They can slow the progression of diabetic nephropathy in patients with Type 1 DM, and of microalbuminuria in those with Type 2 DM, even in the absence of hypertension. Studies have shown a 50% reduction in the risk of the combined end-points of death, dialysis, and renal transplantation in patients with Type 1 DM who were treated with the ACE inhibitor captopril. In addition, ACE inhibitors may prevent development of DM in nondiabetic hypertensive patients. Their potentiation of the effects of bradykinin may account for their ability to enhance insulin sensitivity and may explain their apparent benefit in preventing new-onset Type 2 DM. The usefulness of these agents is limited by their tendency to elevate levels of blood urea nitrogen and creatinine, particularly in conjunction with diuretic therapy and in patients with renal disease or congestive heart failure, and to cause nonproductive cough.
ACE inhibitorAngiotensin-converting enzyme inhibitor. Any of a family of drugs used to manage hypertension and reduce congestive heart failure (CHF)-related mortality and morbidity.
Bepridil, captopril, enalapril, lisionopril, losartan, quinapril, ramipril.
ACE inhibitor Effects in Heart Disease
• Restores balance between myocardial O2 supply and demand;
• Reduces left ventricular preload and afterload;
• Reduces left ventricular mass;
• Reduces sympathetic stimulation.
• Antiproliferative and antimigratory effects on smooth muscle and inflammatory cells;
• Antiplatelet effects;
• Improved arterial compliance and tone;
• Improved and/or restored endothelial function;
• Possible antiatherosclerotic effect.
ACEIs are cardioprotective and vasculoprotective; cardioprotective effects include improved haemodynamics and electric stability, reduce sympathetic nervous system (SNS) activity and reduce left ventricular mass; vasculoprotective benefits include improved endothelial function, vascular compliance and tone, and direct antiproliferative and antiplatelet effects. ACEIs also stimulate prostaglandin (PG) synthesis, reduce the size of MIs, and reduce reperfusion injury and complex ventricular arrhythmias.
ACEIs are the treatment of choice in CHF with systolic dysfunction; they are vasodilators which decrease preload and afterload. ACEI-induced reduction in angiotensin II inhibits the release of aldosterone, which in turn reduces sodium and water retention which, by extension, reduce preload; ACEIs improve haemodynamics of CHF by reducing right atrial pressure, pulmonary capillary wedge pressure, arterial BP, as well as pulmonary and systemic vascular resistance; ACEIs increase cardiac and stroke indices by the left ventricle and reduce the right ventricular end-diastolic volumes, thereby increasing cardiac output, while simultaneously reducing cardiac load and myocardial O2 consumption.
• Idiopathic—e.g., rashes, dysgeusia, BMsuppression.
• Class-specific—e.g., hypotension, renal impairment, hyperkaleamia, cough, angioneurotic oedema (the latter 2 of which are mediated by small vasoactive substances—e.g., bradykinin, substance P, and PG-related factors).
ACE inhibitorAngiotensin-converting enzyme inhibitor Pharmacology Any of a family of drugs that are used to manage essential HTN, ↓ CHF-related M&M Pros ACEIs are cardioprotective and vasculoprotective; cardioprotective effects include improved hemodynamics and electric stability, ↓ SNS activity and ↓ left ventricular mass; vasculoprotective benefits include improved endothelial function, vascular compliance and tone, and direct antiproliferative and antiplatelet effects; ACEIs also stimulate PG synthesis, ↓ the size of MIs, ↓ reperfusion injury and complex ventricular arrhythmias; ACEIs are the treatment of choice in CHF with systolic dysfunction; they are vasodilators which ↓ preload and afterload; ACEI-induced ↓ in angiotensin II inhibits the release of aldosterone, which in turn ↓ sodium and water retention which, by extension, ↓ preload; ACEIs improve hemodynamics of CHF by ↓ right atrial pressure, pulmonary capillary wedge pressure, arterial BP, as well as pulmonary and systemic vascular resistances; ACEIs ↑ cardiac and stroke indices by the left ventricle and ↓ the right ventricular end-diastolic volumes, thereby resulting in ↑ cardiac output, while simultaneously ↓ cardiac load and myocardial O2 consumption; ACEIs also downregulate the SNS, which is linked to the pathogenesis of CHF Adverse effects Idiopathic–eg, rashes, dysgeusia, BM suppression; class-specific–eg, hypotension, renal impairment, hyperkalemia, cough, angioneurotic edema, the latter 2 of which are mediated by small vasoactive substances, eg, bradykinin, substance P, and PG-related factors
ACE inhibitor Effects in Heart Disease
- Restores balance between myocardial O2 supply & demand
- Reduces left ventricular preload and afterload
- Reduces left ventricular mass
- Reduces sympathetic stimulation
- Antiproliferative & antimigratory effects on smooth muscle & inflammatory cells
- Antiplatelet effects
- Improved arterial compliance and tone
- Improved and or restored endothelial function
- Possibly, antiatherosclerotic effect