Brain mineralocorticoid receptor control of blood pressure and kidney function in normotensive rats.
Brain mineralocorticoid receptors appear to contribute to mineralocorticoid hypertension and may be involved in blood pressure control in normotensive rats. We examined the effect of blockade of central mineralocorticoid receptors with the use of a selective antagonist (RU28318) on cardiovascular and renal function in conscious normotensive rats. The contribution of renal innervation was evaluated in rats with bilaterally denervated kidneys. Young adult, male Wistar rats were trained for systolic blood pressure measurement by a tail sphygmographic method and accustomed to metabolic cages for collection of urine. One week before experimentation, an intracerebroventricular cannula was implanted. Systolic blood pressure was diminished 30 minutes after an intracerebroventricular dose of 10 ng of RU28318. The effect was maximal at 8 hours and was still present after 24 hours. Blood pressure returned to the basal level by 48 hours. During the period 0 to 8 hours after intracerebroventricular injection, rats treated with the antagonist showed an increase in diuresis and urinary electrolyte excretion. No significant effect on plasma renin activity, measured 8 and 30 hours after administration of RU28318, was observed. In denervated rats, the decrease in systolic blood pressure after administration of RU28318 was reduced. The difference was statistically significant compared with controls at 2 hours but not at 8 hours, and blood pressure returned to the basal value by 24 hours. The increases in diuresis and urinary electrolyte excretion induced by RU28318 were abolished in denervated rats. These results show that brain mineralocorticoid receptors are involved in blood pressure regulation and kidney function homeostasis in conscious normotensive rats. The renal nerves appear to participate in the brain mineralocorticoid receptor control of blood pressure.
Rahmouni
K
K
Institut de Pharmacologie Laboratoire de Pharmacologie-Physiologie Rénovasculaire, Faculté de Mèdecine, Strasbourg, France.
Barthelmebs
M
M
Grima
M
M
Imbs
J L
JL
Wybren De Jong
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002712:Chlorides / Q000652:urine; D003627:Data Interpretation, Statistical; D003714:Denervation; D004231:Diuresis; D006706:Homeostasis; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D011188:Potassium / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000502:physiology*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
D002712:Chlorides; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; C041006:RU 28318; D012964:Sodium; D012083:Renin; D011188:Potassium