Lecture 9: Renin-Angiotensin

Question 1

aliskiren

Answer 1

Renin inhibitors

Effects: Decreases Blood pressure and renin, no change to HR

Question 2

Losarton

Answer 2

AT1 receptor blocker

Decrease aldosterone secretion
Decrease vasoconstriction
Decrease sympathetic activation

All this resulting in decreased blood pressure

AT2 receptor activation increases

Question 3

ACE inhibitors

Answer 3

Examples: captopril, enalapril, lisinopril

Improves CHF survival, regardless of BP
Increases Bradykinin levels, resulting in increase in Nitric oxide and Prostaglandins

Decreases MAP when Angiotensin I given
Does not change MAP when Angiotensin II given
Does not change MAP when NE given
Increases decrease in MAP when Brady kinin given (enhances bradykinin response)
Does not change loss in MAP when other vasodilators given

SE: Cough and rash (due to elevation in bradykinin), Taste disturbance, rarely an allergic reaction resulting in angioedema (life threatening, and thus CANNOT USE ACE INHIBITOR. CONTRAINDICATION)

Pharmacology:
Racial differences in antihypertensive response (Blacks less response to ACE inhibition or angiotensin renin system. Thus the first antihypertensive you would prescribe is diuretic. Cauc/asian have same response to either)

Question 4

Angiotensin Receptors and Function

Answer 4

AT1
Vasoconstriction
Vascular proliferation
Aldosterone secretion
Cardiac myocyte proliferation
Increased sympathetic tone

AT2
Vasodilation
Antiproliferation
Apoptosis

Angiotensin II binds much more to AT1 than AT2

Angiotensin III can also bind to AT2 and AT1

Question 5

Beta adrenergic antagonists and renin

Answer 5

Propranolol (beta1, beta2 antagonist)
Metoprolol (beta1 antagonist)

Cardiac Beta1 antagonism results in decreased HR
Renal Beta1 antagonism results in decreased renin release
Other–CNS?

Question 6

Bilateral renal artery stenosis

Answer 6

Use of an ACE inhibitor to lower the blood pressure will shut down kidney function. Imaging studies can reveal this condition. Solution is a right renal artery bypass graft, normalizing blood pressure and kidney function.

Question 7

How does AT1 Receptor signaling work

Answer 7

PK-C

Question 8

Aldosterone antagonists

Answer 8

Spironolactone and Eplerenone

This decreases Na+ and H2O reabsorption.
Also inhibits fibrosis, inflammation etc
No effect on ANG II vasoconstriction
Improves mortality rates and reduces symptoms even in presence of an ACE inhibitor (presumably b/c the ACE inhibitor does not knock down Angiotensin II sufficiently to shut down aldosterone production)

Uses:
Diuretic
HTN
Heart Failure

Question 9

Understand the biosynthetic sequence in the formation of angiotensin I and II.

Answer 9

Renin takes Angiotensinogen to Angiotensin I. ACE takes to Angiotensin II. Action on receptors (blocked by ARB) resulting in vasoconstriction and stimulated aldosterone release.

As an aside, Angiotensin III made by angiotensinase A from Angiotensin II