Renin-angiotensin-aldosterone responsiveness to low sodium and blood pressure reactivity to angiotensin-II are unrelated to cholesteryl ester transfer protein mass in healthy subjects.
BACKGROUND
The blood pressure increase associated with the cholesteryl ester transfer protein (CETP) inhibitor, torcetrapib is probably attributable to an off-target effect but it is unknown whether activation of the renin-angiotensin-aldosterone system (RAAS) may be related to variation in the plasma CETP level. We questioned whether the plasma CETP level would affect RAAS responsiveness to low sodium diet and the blood pressure response to angiotensin-II infusion in healthy subjects.


METHODS
RAAS parameters and blood pressure were determined during liberal sodium diet (200 mmol/24 h) and low sodium diet (50 mmol/24 h) in 67 healthy men. Blood pressure response to incremental angiotensin-II infusion was assessed in 34 subjects during liberal sodium diet. Correlation analysis was performed to test whether RAAS responsiveness and blood pressure were related to plasma CETP mass, high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-I measured during liberal sodium diet.


RESULTS
CETP mass ranged from 1.29 to 2.95 mg/l. No significant differences in (changes) in mean arterial pressure, aldosterone and active plasma renin concentration in response to low sodium were observed between the lowest and highest tertiles of CETP mass, HDL-C and apolipoprotein A-I. These outcome variables were also not significantly correlated with CETP, HDL-C and apolipoprotein A-I, except for a modest relation of aldosterone measured during low sodium with apolipoprotein A-I (r = 0.28, p = 0.022). Blood pressure response to angiotensin-II was similar between CETP tertiles.


CONCLUSIONS
Mineralocorticoid and blood pressure responsiveness to dietary salt intake are not significantly related to physiological interindividual differences in plasma CETP. We suggest that a lower CETP mass does not exert adverse effects on blood pressure regulation.
University of Groningen, University Medical Center Groningen, Department of Nephrology, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. j.a.krikken@int.umcg.nl
Jan A
JA
Krikken
Geesje M
GM
Dallinga-Thie
Gerjan
G
Navis
Robin P F
RP
Dullaart
D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology*
D053480:Cholesterol Ester Transfer Proteins; D000804:Angiotensin II; D012964:Sodium