Drugs Acting On RAAS System Flashcards
All three of these compounds are small polypeptides. Which leads to which? Strength of activity?
Angiotensin family. 1 is the precursor to 2, with only weak biology activity. 2 is the strongest; degrades into 3 which is moderate.
What are the most prominent actions of angiotensin 2? How does it cause indirect vasoconstriction?
Vasoconstriction and stimulation of aldosterone release. Acts on vascular smooth muscle; prominent action in arterioles and less so in veins.
Indirectly: acts on sympathetic neurons to promote norepi release, adrenal medulla to promote epi, CNS to increase sympathetic outflow to blood vessels.
The adrenal cortex is highly sensitive to angiotensin 2, hence??
A2 can stimulate aldosterone release even when A2 levels are too low to induce vasoconstriction. Aldosterone secretion is enhanced when Na levels are low and when K is high.
What are examples of pathological changes caused by angiotensin 2?
Cardiac hypertrophy, remodeling, and fibrosis. In HTN, increasing thickness of blood vessel walls. In atherosclerosis, thickening the intimal surface of blood vessels. Increased migration, proliferation, and hypertrophy of vascular smooth muscle cells. Increased production of extra cellular matrix by VSM cells and cardiac fibroblasts.
After being released from the adrenal cortex, aldosterone does what?
Acts on distal tubules of the kidney to cause retention of Na and excretion of K and hydrogen. This increases blood volume and therefore pressure.
Harmful effects of aldosterone (mostly seen in states like heart failure, where levels are super high)
Promote cardiac remodeling and fibrosis. Activate the SNS and suppress uptake of norepi in the heart, predisposing it to dysrhythmias. Promote vascular fibrosis (decreasing arterial compliance), disrupt baroreceptor reflex.
SNS increases secretion by causing stimulation of beta 1 adrenergic receptors on juxtaglomerular cells of kidney, undergoes controlled release into bloodstream where it cleaves angiotensinogen into angiotensin 1.
Renin. Factors that regulate renin release regulate the rate of A2 formation.
What inhibits renin secretion?
Elevation of BP, blood volume, and plasma Na content. Classic negative feedback loop.
Where is ACE located?
Luminal surface of all blood cells, vasculature of the lungs, esp. Cause ACE is so abundant, conversion of A1 into A2 occurs almost immediately after A1 has been formed.
ACE acts on a few substrates. Other names?
When the substrate is A1, the enzyme is called ACE. When the substrate is the hormone bradykinin, the enzyme is called kinase 2.
ACE inhibitors produce their effects by reducing levels of A2 and increasing levels of bradykinin through inhibition of kinase 2. Good effects? Some bad?
Dilate blood vessels (mostly arterioles, to a lesser extent veins), reduce blood volume through effects in the kidney, prevent or reverse pathologic changes in heart and blood vessels mediated by A2 and aldosterone.
Bad are hyperkalemia and fetal injury. Watch for sodium to decrease as well.
