Influence of sodium intake on the cardiovascular and renal effects of brain mineralocorticoid receptor blockade in normotensive rats.
OBJECTIVE
We have previously shown that brain mineralocorticoid receptors (MR) participate in the control of arterial pressure and renal excretory function in normotensive rats. In the present study, we evaluate the influence of sodium intake on the control of cardiovascular and renal function by brain MR in normotensive conscious rats. We hypothesize that modulation of sodium intake affects the cardiovascular and renal effects of brain MR blockade.


METHODS
We examined the effect of intracerebroventricular (ICV) administration of MR antagonist (RU28318) on systolic blood pressure (SBP), heart rate, and urinary excretion of water and electrolytes in normotensive Wistar rats subjected to different dietary sodium content. Rats were fed high (8%), normal (0.4%), or depleted (0%) sodium for 3 weeks. SBP and heart rate measurements were performed using an indirect tail cuff method. Metabolic cages were used to assess renal function.


RESULTS
ICV injection of 100 ng RU28318 induced a long-lasting decrease ( 0.01) in SBP in rats submitted to different sodium intake. At 8 h, the decrease in SBP did not differ between rats on high (30 +/- 5 mmHg), normal (28 +/- 6 mmHg), and low (21 +/- 3 mmHg) sodium diets. At 24 h, the decrease in SBP was also comparable between rats on different sodium diets. Increased diuresis was observed during the period 0-8 h after ICV injection of RU28318; this was less pronounced in rats on the low sodium diet. Urinary excretions of potassium and chloride were also increased during this period, particularly in rats on the high and normal sodium diets compared with rats with low sodium intake. Urinary excretion of sodium was increased only in the rats fed high and normal sodium diets. Measurement of plasma renin activity, which was suppressed and stimulated, respectively, by high and low sodium intake, indicated that the effects on SBP and renal function induced by ICV RU28318 were independent from the level of activation of the renin-angiotensin system.


CONCLUSIONS
In contrast to our hypothesis, in normotensive Wistar rats, sodium intake does not affect the hypotension induced by brain MR blockade. However, sodium depletion attenuated the renal effects of brain MR blockade.
Institut de Pharmacologie, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France. kamal-rahmouni@uiowa.edu
Kamal
K
Rahmouni
Mariette
M
Barthelmebs
Michèle
M
Grima
Jean-Louis
JL
Imbs
Wybren
W
De Jong
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D002712:Chlorides / Q000652:urine; D004039:Diet, Sodium-Restricted; D004231:Diuresis / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D011188:Potassium / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013599:Systole
D002712:Chlorides; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; C041006:RU 28318; D012083:Renin; D011188:Potassium