Low dose of moxonidine within the rostral ventrolateral medulla improves the baroreflex sensitivity control of sympathetic activity in hypertensive rat.
OBJECTIVE
To determine the effects of the centrally antihypertensive drug moxonidine injected into the rostral ventrolateral medulla (RVLM) on baroreflex function in spontaneously hypertensive rats (SHR).


METHODS
Baroreflex sensitivity control of renal sympathetic nerve activity (RSNA) and barosensitivity of the RVLM presympathetic neurons were determined following application of different doses of moxonidine within the RVLM.


RESULTS
Three doses (0.05, 0.5, and 5 nmol in 50 nL) of moxonidine injected bilaterally into the RVLM dose-dependently reduced the baseline blood pressure (BP) and RSNA in SHR. At the highest dose (5 nmol) of moxonidine injection, the maximum gain (1.24%+/-0.04%/mmHg) of baroreflex control of RSNA was significantly decreased. However, the lower doses (0.05 and 0.5 nmol) of moxonidine injection into the RVLM significantly enhanced the baroreflex gain (2.34%+/-0.08% and 2.01%+/-0.07%/mmHg). The moxonidine-induced enhancement in baroreflex function was completely prevented by the imidazoline receptor antagonist efaroxan but not by the alpha(2)-adrenoceptor antagonist yohimbine. A total of 48 presympathetic neurons were recorded extracellularly in the RVLM of SHR. Iontophoresis of applied moxonidine (30-60 nA) dose-dependently decreased the discharge of RVLM presympathetic neurons but also significantly increased the barosensitivity of RVLM presympathetic neurons.


CONCLUSIONS
These data demonstrate that a low dose of moxonidine within the RVLM has a beneficial effect on improving the baroreflex function in SHR via an imidazoline receptor-dependent mechanism.
Wang
Jia-ling
JL
Department of Physiology, Second Military Medical University, Shanghai, China.
Wang
Long
L
Wu
Zhao-tang
ZT
Yuan
Wen-jun
WJ
Su
Ding-feng
DF
Ni
Xin
X
Yan
Jian-jun
JJ
Wang
Wei-zhong
WZ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001572:Benzofurans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007478:Iontophoresis; D007668:Kidney / Q000294:innervation / Q000502:physiology; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D008845:Microinjections; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D055366:Synaptic Potentials / Q000187:drug effects* / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D015016:Yohimbine; C043482:moxonidine; C062597:efaroxan