Hypothalamic GABA suppresses sympathetic outflow to the cardiovascular system

1988 ◽  
Vol 254 (4) ◽  
pp. R680-R687 ◽  
Author(s):  
J. H. Wible ◽  
F. C. Luft ◽  
J. A. DiMicco

We studied the cardiovascular effects of altering GABA-ergic tone in the posterior hypothalamus in rats. Animals were equipped with chronic guide cannulas placed in the posterior hypothalamus, arterial and venous catheters, and a bipolar electrode on the splanchnic nerve. Microinjected bilaterally into the posterior hypothalamus in conscious rats, the postsynaptic gamma-aminobutyric acid (GABA) antagonists bicuculline methiodide and picrotoxin rapidly increased heart rate, blood pressure, and sympathetic nerve activity. Microinjection of the GABA agonist muscimol into this same region decreased heart rate, blood pressure, and sympathetic nerve activity in conscious rats. In contrast, muscimol infused into the posterior hypothalamus of anesthetized rats failed to alter heart rate or blood pressure. We conclude that 1) the posterior hypothalamus contains a sympathoexcitatory system that is modulated by changes in GABA-ergic tone and 2) tonic GABA-ergic inhibition is sufficient to completely suppress the activity of this hypothalamic sympathoexcitatory system in anesthetized animals but not in conscious rats.

1992 ◽  
Vol 263 (5) ◽  
pp. H1348-H1355 ◽  
Author(s):  
P. B. Persson ◽  
H. Stauss ◽  
O. Chung ◽  
U. Wittmann ◽  
T. Unger

This study tests whether the power spectrum of blood pressure (BP) provides information toward the sympathovagal balance of BP control by comparing the BP (femoral arterial catheter) spectrum with the spectrum of the efferent sympathetic nerve activity (SNA, bipolar electrode around splanchnic nerve). A remarkable resemblance between both spectra was found. A high-frequency component (HF) linked to respiration and a slower fluctuation type between 0.15 and 0.6 Hz (LF) were identified. There was a large and significant coherence only in the HF range of the BP and SNA power spectrum (P < 0.01). The phase lag of SNA and BP was roughly 200 ms. The recordings were repeated during pharmacological blockade in nine Wistar-Kyoto rats (WKY) and nine spontaneously hypertensive rats (SHR). alpha 1-Adrenoceptor blockade (prazosin) reduced the proportional LF power of BP in both rat strains (WKY P < 0.01, SHR P < 0.05) in favor of HF (WKY P < 0.01, SHR P < 0.01). Parasympathetic blockade (methylscopolamine) had no effect on proportions of power. Similarly, there were no significant differences in the proportional HF and LF power spectra of WKY and SHR. These data provide direct evidence for a relationship between the BP and SNA power spectra; however, only the acute changes in the sympathetic tone changed the LF-HF relationship.


2013 ◽  
Vol 305 (8) ◽  
pp. H1238-H1245 ◽  
Author(s):  
Christopher E. Schwartz ◽  
Elisabeth Lambert ◽  
Marvin S. Medow ◽  
Julian M. Stewart

Withdrawal of muscle sympathetic nerve activity (MSNA) may not be necessary for the precipitous fall of peripheral arterial resistance and arterial pressure (AP) during vasovagal syncope (VVS). We tested the hypothesis that the MSNA-AP baroreflex entrainment is disrupted before VVS regardless of MSNA withdrawal using the phase synchronization between blood pressure and MSNA during head-up tilt (HUT) to measure reflex coupling. We studied eight VVS subjects and eight healthy control subjects. Heart rate, AP, and MSNA were measured during supine baseline and at early, mid, late, and syncope stages of HUT. Phase synchronization indexes, measuring time-dependent differences between MSNA and AP phases, were computed. Directionality indexes, indicating the influence of AP on MSNA (neural arc) and MSNA on AP (peripheral arc), were computed. Heart rate was greater in VVS compared with control subjects during early, mid, and late stages of HUT and significantly declined at syncope ( P = 0.04). AP significantly decreased during mid, late, and syncope stages of tilt in VVS subjects only ( P = 0.001). MSNA was not significantly different between groups during HUT ( P = 0.700). However, the phase synchronization index significantly decreased during mid and late stages in VVS subjects but not in control subjects ( P < .001). In addition, the neural arc was significantly affected more than the peripheral arc before syncope. In conclusion, VVS is accompanied by a loss of the synchronous AP-MSNA relationship with or without a loss in MSNA at faint. This provides insight into the mechanisms behind the loss of vasoconstriction and drop in AP independent of MSNA at the time of vasovagal faint.


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Jian Cui ◽  
Matthew D Muller ◽  
Allen R Kunselman ◽  
Cheryl Blaha ◽  
Lawrence I Sinoway

Epidemiological data suggest that blood pressure tends to be higher in winter and lower in summer, particularly in the elderly. Moreover, hospitalization and mortality rates due to cardiovascular disease have higher rates in winter than summer. Whether autonomic adjustment including muscle sympathetic nerve activity (MSNA) varies with season is unclear. To test the hypothesis that resting MSNA varies along the seasons, we retrospectively analyzed the supine baseline (6 min) MSNA and heart rate (from ECG) of 57 healthy subjects (33M, 24F, 29 ± 1 yrs, range 22-64 yrs) from studies in our laboratory (room temperature ~23 °C). Each of these subjects from central Pennsylvania was studied during 2 or more seasons (total 231 visits). A linear-mixed effects model, which is an extension of the analysis of variance model accounting for repeated measurements (i.e. season) per subject, was used to assess the association of season with the cardiovascular outcomes. The Tukey-Kramer procedure was used to account for multiple comparisons testing between the seasons. MSNA burst rate in winter (21.3 ± 1.0 burst/min) was significantly greater than in summer (13.7 ± 1.0 burst/min, P < 0.001), spring (17.5 ± 1.6 burst/min, P = 0.04) and fall (17.0 ± 1.2 burst/min, P < 0.002). There was no significant difference in MSNA in other comparisons (spring vs. summer, P = 0.12; spring vs. fall, P = 0.99; summer vs. fall, P = 0.054). Heart rate (63.6 ± 1.1 vs. 60.8 ± 1.2 beats/min, P = 0.048) was significantly greater in winter compared to summer. Blood pressure (automated sphygmomanometry of the brachial artery) was not significantly different between seasons. The results suggest that baseline sympathetic nerve activity varies along the seasons, with peak levels evident in winter. We speculate that the seasonal MSNA variation may contribute to seasonal variations in cardiovascular morbidity and mortality.


1989 ◽  
Vol 67 (1) ◽  
pp. 250-255 ◽  
Author(s):  
J. P. Fluckiger ◽  
G. Gremaud ◽  
B. Waeber ◽  
A. Kulik ◽  
A. Ichino ◽  
...  

A new system was developed in our laboratory to continuously monitor intra-arterial pressure, heart rate, and sympathetic nerve activity in unanesthetized rats. The animals were prepared 24 h before the start of the experiments. Sympathoneural traffic was measured at the level of splanchnic nerve. The amplitude of the spikes recorded at this level was utilized to express sympathetic nerve activity. The amplitude of the residual electroneurogram signal present 30 min after the rats were killed was 32 +/- 2 mV (mean +/- SE; n = 11). For analysis, these background values were subtracted from values determined in vivo. The nerve we studied contains postganglionic fibers, since electrical activity decreased in response to ganglionic blockade with pentolinium (1.25 mg/min iv for 4 min). The amplitude of spikes fell by 43 +/- 4% (n = 4). Sympathetic nerve activity was highly reproducible at a 24-h interval (104 +/- 26 vs. 111 +/- 27 mV for the amplitude of spikes; n = 11). Dose-response curves to the alpha 1-stimulant methoxamine and to bradykinin were established in four rats. The increase in blood pressure induced by methoxamine caused a dose-dependent fall in sympathetic nerve activity, whereas the blood pressure reduction resulting from bradykinin was associated with a dose-dependent activation of sympathetic drive. These data therefore indicate that it is possible with out system to accurately measure sympathetic nerve activity in the awake rat, together with intra-arterial pressure and heart rate.


2000 ◽  
Vol 84 (6) ◽  
pp. 2859-2867 ◽  
Author(s):  
Takato Kunitake ◽  
Hiroshi Kannan

We investigated the periodic characteristics of bursting discharge in renal sympathetic nerve activity (RSNA) in conscious rats. Employing a discrete fast Fourier transform algorithm, a power spectrum analysis was used to quantify periodicities present in rectified and integrated RSNA whose signal-to-noise ratio in the recordings was greater than six. In conscious rats with intact baroreceptors, RSNA was characterized by four frequency components occurring at about 0.5, 1.5, 6, and 12 Hz, which corresponded to the low-frequency fluctuation of heart rate, respiration, and frequency of heart beat, and its harmonics, respectively. After intravenous infusion of sodium nitroprusside (SNP) to elicit reflex increases in RSNA and heart rate, the power for the component at 6 Hz followed the changes in heart beat frequency and was significantly increased, while those for the three other components were attenuated or experienced no change. In sino-aortic denervated (SAD) conscious rats, all four components were abolished, and the power spectrum was well fitted by a flat or Lorentzian curve, suggesting an almost random pattern. Only a respiratory-related component, which suggested common central modulation, appeared sporadically for short periods but was absent for the most part. Therefore most of this component together with the low-frequency component was also likely due to the baroreceptor-dependent peripheral modulation. The activity was sorted in 15 subgroups on the basis of spike amplitudes in the RSNA. Each subgroup showed frequency characteristics similar to the whole nerve activity. These results suggest that all periodicity in the RSNA of conscious rats with intact baroreceptors is caused by the baroreceptor input.


2011 ◽  
Vol 300 (6) ◽  
pp. R1437-R1442 ◽  
Author(s):  
Helen Jones ◽  
Nia C. S. Lewis ◽  
Daniel J. Green ◽  
Philip N. Ainslie ◽  
Samuel J. E. Lucas ◽  
...  

Early morning reduction in endothelium-dependent, flow-mediated dilation (FMD) may contribute to the high incidence of sudden cardiac death at this time of day. The mechanisms underpinning diurnal variation in FMD are unclear, but potentially relate to a circadian rhythm in sympathetic nerve activity. We hypothesized that blockade of α1-mediated sympathetic nerve activity would act to attenuate the diurnal variation in FMD. In a randomized and placebo-controlled design, we measured brachial artery FMD in 12 participants (mean age = 26 yr, SD = 3) at 0600 and 1600 after ingestion of an α1-blocker (prazosin, 1 mg/20 kg body mass) or placebo. Arterial diameter and shear rate were assessed using edge-detection software. Heart rate and blood pressure were also measured. Data were analyzed using linear mixed modeling. Following placebo, FMD was 8 ± 2% in the morning compared with 10 ± 3% in the afternoon ( P = 0.04). Blockade with prazosin led to a slight but nonsignificant increase in morning FMD ( P = 0.24) and a significant ( P = 0.04) decrease in afternoon FMD, resulting in no diurnal variation ( P = 0.20). Shear rate did not differ in the morning or afternoon under either condition ( P > 0.23). Blood pressure was lower following prazosin compared with placebo ( P < 0.02), an effect that was similar at both times of day ( P > 0.34). Heart rate and norepinephrine levels were higher in the afternoon following prazosin. These data indicate that α1-adrenoreceptor activity does not explain lower morning endothelium-dependent FMD.


1990 ◽  
Vol 183 (3) ◽  
pp. 835-836
Author(s):  
M. Minami ◽  
H. Matsuda ◽  
H. Sato ◽  
N. Yamazaki ◽  
H. Togashi ◽  
...  

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