Influence of sodium intake on the cardiovascular and renal effects of brain mineralocorticoid receptor blockade in normotensive rats

• Published in: Journal of hypertension Vol. 20; no. 9; pp. 1829 - 1834
• Main Authors: Rahmouni, Kamal, Barthelmebs, Mariette, Grima, Michèle, Imbs, Jean-Louis, De Jong, Wybren
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01-09-2002; Lippincott Williams & Wilkins
• Subjects: Animals; Biological and medical sciences; Blood Pressure - drug effects; Blood vessels and receptors; Cardiovascular System - drug effects; Chlorides - urine; Diet, Sodium-Restricted; Diuresis - drug effects; Fundamental and applied biological sciences. Psychology; Heart Rate - drug effects; Injections, Intraventricular; Male; Mineralocorticoid Receptor Antagonists; Potassium - urine; Rats; Rats, Wistar; Renin - blood; Spironolactone - administration & dosage; Spironolactone - analogs & derivatives; Spironolactone - pharmacology; Systole; Vertebrates: cardiovascular system; Pharmacologic test; Renal function; Rat; Mineralocorticoid; Rodentia; Exploration; Aldosterone; Heart rate; Vertebrata; Regulation(control); Mammalia; Diet; Mineralocorticoid receptor; Animal; Sodium ion; Intracerebral administration; Blood pressure; Antagonist; Comparative study
• ISSN: 0263-6352; 1473-5598
• DOI: 10.1097/00004872-200209000-00029

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.
DESIGN AND METHODSWe 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 (P < 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.
CONCLUSION 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.