ACE inhibitors produce vasodilation by inhibiting the formation of angiotensin II. This vasoconstrictor is formed by the proteolytic action of renin (released by the kidneys) acting on circulating angiotensinogen to form angiotensin I. Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme.
ACE also breaks down bradykinin (a vasodilator substance). Therefore, ACE inhibitors, by blocking the breakdown of bradykinin, increase bradykinin levels, which can contribute to the vasodilator action of ACE inhibitors. The increase in bradykinin is also believed to be responsible for a troublesome side effect of ACE inhibitors, namely, a dry cough.
Angiotensin II constricts arteries and veins by binding to AT1 receptors located on the smooth muscle, which are coupled to a Gq-protein and the the IP3 signal transduction pathway. Angiotensin II also facilitates the release of norepinephrine from sympathetic adrenergic nerves and inhibits norepinephrine reuptake by these nerves. This effect of angiotensin II augments sympathetic activity on the heart and blood vessels.
Cardiorenal Effects of ACE Inhibitors
- Vasodilation (arterial & venous)
– reduce arterial & venous pressure
– reduce ventricular afterload & preload - Decrease blood volume
– natriuretic
– diuretic - Depress sympathetic activity
- Inihibit cardiac and vascular hypertrophy
Therapeutic Use of
ACE Inhibitors
- Hypertension- in conjunction with diuretic
- Heart failure-
- reduces afterload
- increases stroke volume and increased ejection fraction.
- Reduces Preload and decreases pulmonary and systemic congestion and Edema.
- Improving the oxygen supply/demand ratio primarily by decreasing demand through the reductions in afterload and preload.
- Prevents angiotensin II from triggering deleterious cardiac remodeling. (scarring)
- Post-myocardial infarction
ACE Inhibitor List
benazepril
captopril
enalapril
fosinopril
lisinopril
moexipril
quinapril
ramipril
