Posts Tagged ‘Response to angiotensin-converting enzyme inhibition is selectively blunted by high sodium in angiotensin-converting enzyme DD genotype: evidence for gene–environment interaction in healthy volunteers’
woensdag, december 7th, 2011
| Title | Response to angiotensin-converting enzyme inhibition is selectively blunted by high sodium in angiotensin-converting enzyme DD genotype: evidence for gene–environment interaction in healthy volunteers |
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| Year | 2010 |
| Estimated date | 2010-04-01 |
| Category | Scientific Publication |
| Platform | None |
| Description | Background Renin–angiotensin–aldosterone system
blockade is a cornerstone in cardiovascular protection.
Angiotensin-converting enzyme (ACE)-DD genotype has
been associated with resistance to angiotensin-converting
enzyme inhibition (ACEi), but data are conflicting. As
sodium intake modifies the effect of ACEi as well as the
genotype–phenotype relationship, we hypothesize gene–
environment interaction between sodium-status, the
response to ACEi, and ACE genotype.
Method Thirty-five male volunteers (26W9 years; II nU6, ID
nU18, DD nU11) were studied during placebo and ACEi
(double blind, enalapril 20mg/day) on low [7 days 50mmol
Naþ/day (lowsalt)]andhigh[7 days 200mmolNaþ/day (high
salt)] sodium, with a washout of 6 weeks in-between. After
each period mean arterial pressure (MAP) was measured
before and during graded infusion of angiotensin II (Ang II).
Results During high salt, ACEi reduced MAP in II and ID, but
not in DD [II: 88 (78–94) versus 76 (72–88); ID: 87 (84–91)
versus 83 (79–87); both P<0.05 and DD: 86 (82–96) versus
88 (80–90); ns, P<0.05 between genotypes]. However,
during low salt, ACEi reduced MAP in all genotype groups [II:
83 (78–89) versus 77 (72–83); ID: 88 (84–91) versus 82 (78–
86); DD: 84 (80–91) versus 81 (75–85); all P<0.05]. During
high saltRACEi, the Ang II response was blunted in DD, with
an 18% rise in MAP during the highest dose versus 22 and
31% in ID and II (P<0.05). Low salt annihilated these
differences.
Conclusion In healthy participants, the MAP response to
ACEi is selectively blunted in DD genotype during high salt,
accompanied by blunted sensitivity to Ang II. Low salt
corrects both abnormalities. Further analysis of this gene–
environment interaction in patients may contribute to
strategies for improvement of individual treatment efficacy.
J Hypertens 28:2414–2421 Q 2010 |
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Tags: 2010, None, Response to angiotensin-converting enzyme inhibition is selectively blunted by high sodium in angiotensin-converting enzyme DD genotype: evidence for gene–environment interaction in healthy volunteers, Scientific Publication
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