Cardiovascular Adaptation: Hypo and Hypertension

Question 1

Ortlepp, 2002

Answer 1

RAAS mutations predispose to Cardiovascular Disease and Hypertension:
Angiotensinogen M235T missense in exon 2
ACE 1 287 base pair deletion in intron 16
AT1 Receptor A1166C missense

Question 2

Coleridge, 1981

Answer 2

Chronic hypertension causes Baroceptors to adopt a new ‘Set Point’ meaning their threshold for firing is higher and they no longer generate an error signal towards elevated blood pressure

Question 3

Koch, 1931

Answer 3

Demonstrated that baroceptor reflexes control blood pressure

Question 4

UK Health Survey, 2008

Answer 4

1 in 4 UK adults has Hypertension, this increases to 1 in 2 over 60 years old

Question 5

Fyhrquist, 2008

Answer 5

Multiple angiotensin peptides are produced from Angiotensin I and Angiotensin II using enzymes such as AMPM, AMPA, ACE 2 and NEP. These peptides are Angiotensin III-VII.
Angiotensin III and IV notably oppose the effects of Angiotensin II.

Question 6

Santos, 2003

Answer 6

The AT1 receptor is responsible for hypertrophy of vasculature and cardiac fibrosis. MAS1 is an oncogene that codes for the GPCR AT3. This receptor binds all Angiotensin peptides I-VII and actively opposes the effects of AT1. So agonists of AT3 could be used as therapeutics for hypertension

Question 7

PARADIGM Trial, 2013

Answer 7

This trial showed the effectiveness of Entresto-a neprilysin inhibitor