Aldosterone is synthesized in and activates bulbospinal neurons through mineralocorticoid receptors and ENaCs in the RVLM.
The effects of aldosterone and mineralocorticoid receptor (MR) blockers on presympathetic neurons in the rostral ventrolateral medulla (RVLM) are well studied. To directly investigate whether aldosterone, eplerenone (an MR blocker), FAD286 (an aldosterone synthase inhibitor) and benzamil (an epithelial sodium channel (ENaC) blocker) affect RVLM neurons, we examined changes in the membrane potentials (MPs) of bulbospinal RVLM neurons using the whole-cell patch-clamp technique during superfusion with these drugs to brainstem-spinal cord preparations. Aldosterone superfusion (0.1 μmol/l) depolarized the RVLM neurons. In contrast, eplerenone superfusion (1 μmol/l) hyperpolarized them. To evaluate the existence of aldosterone, FAD286 superfusion (10 μmol/l) was performed, and the RVLM neurons became hyperpolarized during FAD superfusion. These data suggest that MRs exist and that aldosterone is synthesized in the brainstem. Benzamil superfusion (1 μmol/l) hyperpolarized the RVLM neurons. To clarify whether aldosterone, eplerenone, FAD286 and benzamil acted directly on the RVLM neurons, a low-Ca(2+), high-Mg(2+) solution was used to block the synaptic input to the RVLM neurons, and the above-mentioned drugs were added during the low-Ca(2+) superfusion. During the aldosterone superfusion, the RVLM neurons became depolarized, and they became hyperpolarized during eplerenone, FAD286 or benzamil superfusion. Importantly, when aldosterone was superfused after the benzamil solution, the MPs of the RVLM neurons did not depolarize. These results suggest that MRs are present in the RVLM neurons and that aldosterone is synthesized in the RVLM. The RVLM neurons themselves possess ENaCs, and ENaCs are the underlying mechanism by which aldosterone activates RVLM neurons.
Department of Nephrology and Endocrinology, National Defense Medical College, Tokorozawa, Japan. oshima@ndmc.ac.jp
Naoki
N
Oshima
Hiroshi
H
Onimaru
Hanako
H
Takechi
Kojiro
K
Yamamoto
Atsushi
A
Watanabe
Takahiro
T
Uchida
Yasuhiro
Y
Nishida
Takashi
T
Oda
Hiroo
H
Kumagai
D000450:Aldosterone / Q000096:biosynthesis* / Q000502:physiology*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D047072:Aromatase Inhibitors / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000502:physiology*; D000077545:Eplerenone; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D017316:Fadrozole / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008526:Medulla Oblongata / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology* / Q000502:physiology*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D016707:Tissue Fixation
D047072:Aromatase Inhibitors; D004232:Diuretics; D053503:Epithelial Sodium Channels; D018161:Receptors, Mineralocorticoid; C013407:benzamil; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D000584:Amiloride; D017316:Fadrozole; D008274:Magnesium; D002118:Calcium