Effects of statins on renal sodium and water handling: acute and short-term effects of atorvastatin on renal haemodynamics, tubular function, vasoactive hormones, blood pressure and pulse rate in healthy, normocholesterolemic humans.
BACKGROUND
Statins have a beneficial effect on cardiovascular morbidity and mortality due to a reduction in plasma cholesterol. However, statins seem to have effects beyond the lowering of plasma cholesterol. We hypothesize that these effects are caused by an effect on renal function.


METHODS
We measured the effects of atorvastatin (AS) on renal function in two randomized, placebo-controlled, double-blinded and crossover studies in healthy man. In an acute trial (Study 1), 19 subjects received either 80 mg AS as a single dose or placebo. In a short-term trial (Study 2), 20 subjects received either 80 mg AS or placebo daily for 4 weeks. In both studies glomerular filtration rate (GFR), renal plasma flow (RPF), plasma concentrations of angiotensin II (Ang II), renin (PRC), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), aldosterone (Aldo), vasopressin (AVP) and blood pressure (BP) were determined.


RESULTS
In Study 1 AS decreased fractional excretion of sodium (FE(Na)) significantly (P = 0.035), but very modestly, and reduced diastolic BP (P = 0.024). Apart from this, we found no significant differences in GFR, RPF, tubular function and vasoactive hormones in either Study 1 or 2.


CONCLUSIONS
An acute dose of AS decreased FE(Na) and DBP in healthy humans. The reduction in fractional urinary sodium excretion was very modest and transitory, and most likely secondary to the fall in diastolic blood pressure (DBP). However, renal haemodynamics, tubular function, vasoactive hormones and blood pressure were unchanged during short-term statin treatment in healthy man.
Paulsen
Lone
L
Department of Medical Research, Holstebro Hospital, Laegårdvej 12, DK-7500 Holstebro, Denmark.
Holm
Charlotte
C
Bech
Jesper Nørgaard
JN
Starklint
Jørn
J
Pedersen
Erling Bjerregaard
EB
D000328:Adult; D000804:Angiotensin II / Q000097:blood; D001127:Arginine Vasopressin / Q000097:blood; D000069059:Atorvastatin; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004231:Diuresis / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology*; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D017595:Renal Plasma Flow / Q000187:drug effects
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000804:Angiotensin II; D001127:Arginine Vasopressin; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D000069059:Atorvastatin