Autoimmune Thyroid Disease

An Unfortunate and Lengthy Adventure in Misdiagnosis

ACE interactions

with 3 comments

Angiotensin I-converting enzyme (ACE) is a zinc metallopeptidase whose main known functions are to convert angiotensin I into the vasoactive and aldosterone-stimulating peptide angiotensin II, and to inactivate bradykinin. ACE is believed to have other physiological roles because of its wide enzymatic specificity and wide distrubution. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.

Analysis of ACE genotypes reveal[s] that patients with the wild type ACE gene (ACE I/I) have normal angiotensin II levels, while patients with a deletion in both alleles (ACE D/D) have far higher levels, and those with a single allele deletion have intermediate levels. New Approaches to Heart Failure: From Pharmacogenomics to Drug Development

Mild quantitative changes in the expression of ACE do not affect plasma angiotensin II level or BP because of the concomitant changes in the level of angiotensin I. However, plasma [bradykinin] level changes with changes in ACE expression. Minireview: Computer Simulations of Blood Pressure Regulation by the Renin-Angiotensin System

D/D homozygotes have a 25% increase, and I/I homozygotes have a 25% decrease in plasma ACE activity relative to the I/D heterozygotes. In otherwords, feedback causes angiotensin I levels to lower to maintain correct angiotensin II levels. Examine Figure 3B in the minireview linked to above. It displays D/D types as having lower angiotensin I levels whilst maintaining relatively normal angiotensin II levels.

Now check out the interaction with monoamine oxidase:

It is concluded that diminished [angiotensin I] receptor stimulation decreases cardiac MAO activity, probably by regulating MAO expression, since ANG, ACE inhibitors, and AT(1) antagonists had no effect on MAO activity in vitro. Angiotensin I-converting enzyme inhibition increases cardiac catecholamine content and reduces monoamine oxidase activity via an angiotensin type 1 receptor-mediated mechanism.

Stressed all the time?

Angiotensin II increases thirst sensation[…] It also potentiates the release of norepinephrine by direct action on postganglionic sympathetic fibers. Angiotensin Wiki

Another interaction with COMT:

Angiotensin-converting enzyme (ACE) modulates dopamine turnover in the brain and catechol-O-methyltransferase (COMT) enzyme is an important agent in the metabolic inactivation of dopamine and norepinephrine. Functional polymorphism in the COMT and ACE genes causes variation in enzyme activities. We investigated the relationship of COMT and ACE gene polymorphism with response to conventional neuroleptic treatment in schizophrenia. In this study population we had earlier detected that COMT genotype is associated with unsatisfactory drug response. A total of 94 schizophrenic patients were evaluated either as responders (n=43) or non-responders (n=51). The responders had experienced a fair and steady response to conventional neuroleptics. The non-responders had failed to achieve an acceptable response to conventional neuroleptics. We also used a control population of 94 age- and gender-matched blood donors. Genotyping of the COMT and ACE genes was performed by polymerase chain reaction. The risk of having both low activity COMT and high activity ACE genotypes was over 10 times higher (odds RATIO=10.89, 95%CI 1.14–103.98, P=0.04) in the non-responders compared to responders. ACE genotype alone did not differ between any groups. This finding may suggest a possible interaction with low activity COMT and high activity ACE genotype in association with poor response to conventional neuroleptics. Interaction between angiotensin-converting enzyme and catechol-O-methyltransferase genotypes in schizophrenics with poor response to conventional neuroleptics

One interesting fact I stumbled upon recently is that a low sodium diet increases monoamine oxidase activity in rats, and this operates via an angiotensin II mechanism. So does a high sodium diet decrease monoamine oxidase activity?

And check out the interaction with vitamin D receptors:

Mice lacking the Vitamin D receptor (VDR) have elevated production of renin and angiotensin (Ang) II, leading to hypertension, cardiac hypertrophy and increased water intake. These abnormalities can be prevented by treatment with an ACE inhibitor or AT(1) receptor antagonist. Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure

In fact the lower your vitamin D levels the higher your whole renin-angiotensin sytem. Vitamin D is an extremely effective way to lower your blood pressure.


Written by alienrobotgirl

19 April, 2008 at 3:48 pm

Posted in The Genetics of FCI?

Tagged with ,

3 Responses

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  1. Explains a few things about my amine sensitivity then. 🙂

    Except with all those mutations I still have low blood pressure 90/60 at rest. However i’m pretty sure my blood pressure spikes sometimes which might explain my random bouts of chest pain or ‘cranial pressure’.

    I’ve disliked salt for as long as I remember. I would always make sure I get those crisps with the little salt sachets so I could eat them plain.



    20 April, 2008 at 9:40 am

  2. This is bending my head.

    ACE inhibition or (genetically) low ACE activity both should reduce Ang II, but this is prevented by feedback which increases Ang I to maintain normal Ang II levels. OK?

    Increased Ang I acts to decrease cardiac MAO activity, thus increases cardiac catecholamine levels. This is suggested to be good.

    Angiotensin II, pathologically, increases release of norepinephrine from post synaptic sympathetic neurones. True.

    OK, how does decreased catecholamine breakdown (ultimately from ACE inhibition etc in this discussion) differ from increased norepinephrine release (from Ang II acting on the sympathetic nervous system)?

    In general ACE inhibition=good and increased SNS activity =bad…. Is this a square circle or am I missing a negative somewhere?



    22 April, 2008 at 3:29 pm

  3. LOL, Peter, I have no idea why increasing catecholamines is suggested to be good! In general there seems to be a pro-MAO inhibition prejudice in a lot of papers that I think is a bit of a hangover from the good bad old days of prescription MAOIs for depression. It’s certainly not good when a bit of tyramine in cheese gives you heart palpitations!

    Almost everyone food chemical intolerant who gets their genetics done comes back homozygous for an ACE deletion (including Elena above!). There’s something massive going on, and ACE seems to be a key player.


    22 April, 2008 at 6:04 pm

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