Low dose of moxonidine within the rostral ventrolateral medulla improves the baroreflex sensitivity control of sympathetic activity in hypertensive rat
Abstract
Aim: 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 α2-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.
Conclusion: 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.
Keywords:
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 α2-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.
Conclusion: 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.