Angiotensin-Aldosterone System: A Summary

Angiotensin Converting Enzyme (ACE) inhibitors lower blood pressure and produce vasodilation by inhibiting ACE – blocking the conversion of angiotensin I to angiotensin II, key mediators of the Renin-Angiotensin-Aldosterone System (RAAS). RAAS is the main mechanism for controlling BP. Angiotensin II is a vasoconstrictor and works by binding to angiotensin I receptors on smooth muscle – these are joined to a Gq protein and the IP3 signal transduction pathway. ACE usually breaks down bradykinin. Bradykinin is a vasodilator. Therefore as ACE is inhibited the breakdown of bradykinin does not occur – leading to the body having higher levels of bradykinin. This mechanism is what gives ACE inhibitors their vasodilation effect. This reduces arterial …show more content…
The job of L-type channels is to control calcium entry into the cell. This leads to stimulation of smooth muscle and cardiac myocytes contraction. Calcium channel antagonists prevent the opening of L-type channels in excitable tissues in response to depolarisation – as a result the limit the increase of Ca2+. L-type channels control the upstroke of action potential in the SA and AV nodes and also mediate phase 2 of ventricular action potential. Thus, by blocking the entry of calcium into cells calcium channel antagonists cause vasodilation and decreased: myocardial force generation, conduction velocity (particularly the AV node) and heart rate. This is negative inotropy, dromotropy and chronotropy respectively. Therefore calcium channel antagonists lower systemic vascular resistance by causing vasodilation. In turn, this lowers MAP. The major effect of calcium channel antagonists is on the arterioles/arteries with little effect on veins. Moreover, drugs with selectivity for smooth muscle L-type channels (for example, amlodipine) are preferential to lower the risk of unwanted effects on cardiac muscle – this is particularly important in patients with hypertension and heart failure, or heart