[Brain mineralocorticoid receptor and blood pressure control in the conscious normotensive rat].
Brain control of arterial blood pressure in man and in animals has been studied increasingly over the last few decades. Despite our knowledge about short term regulation (chemoreceptor and baroreceptor reflexes) there is much more uncertainty about the degree of involvement of brain mechanisms in long term control of blood pressure, and in hypertension. The last decade, a role of brain mineralocorticoid receptors (MR) has been outlined in animal experiments. Stimulation of brain MR by aldosterone or related mineralocorticoids induces an increase in blood pressure and hypertension under chronic conditions. These effects of mineralocorticoid excess can be blocked by specific MR antagonists administered centrally. Stimulation of brain glucocorticoid receptors, as compared to stimulation of brain MR, has an opposite effect, i.e. decreases blood pressure. As in the typical peripheral target organs of aldosterone, in the brain, enzymatic protection of MR against glucocorticoids appears to play an important role. We showed that in conscious normotensive rats intracerebroventricular (i.c.v.) injection of a specific MR antagonist (RU28318) in a low dose (10 ng) decreases blood pressure by about 20% without affecting heart rate. A similar but smaller effect (not statistically significant) was observed in conscious female rats. Only in the male rats an increased diuresis occurred and this may have contributed to the observed hypotension. We conclude that hypertension caused by mineralocorticoid excess may depend on a concerted action of the steroid on the kidney and on the brain. The mechanism by which brain MR increases blood pressure is unknown. It is possible that increased sympathetic outflow and renal mechanisms are involved. Interference with brain MR not only affects blood pressure but it also has effect on renal function.
Rahmouni
K
K
Institut de pharmacologie, Faculté de médecine, Université Louis-Pasteur, Strasbourg.
Barthelmebs
M
M
Imbs
J L
JL
De Jong
W
W
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000502:physiology*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; C041006:RU 28318