Stimulation of cardiac sympathetic nerve activity by central angiotensinergic mechanisms in conscious sheep

2004 ◽  
Vol 286 (6) ◽  
pp. R1051-R1056 ◽  
Author(s):  
Anna M. D. Watson ◽  
Rasim Mogulkoc ◽  
Robin M. McAllen ◽  
Clive N. May
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Hypertonic Saline ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Ang Ii ◽  
Cardiac Sympathetic Nerve ◽  
Nerve Activity ◽  
Cardiac Sympathetic Nerve Activity ◽  
Conscious Sheep

Central actions of angiotensin play an important role in cardiovascular control and have been implicated in the pathogenesis of hypertension and heart failure. One feature of centrally or peripherally administered angiotensin is that the bradycardia in response to an acute pressor effect is blunted. It is unknown whether after central angiotensin this is due partly to increased cardiac sympathetic nerve activity (CSNA). We recorded CSNA and arterial pressure in conscious sheep, at least 3 days after electrode implantation. The effects of intracerebroventricular infusions of ANG II (3 nmol/h for 30 min) and artificial cerebrospinal fluid (CSF) (1 ml/h) were determined. The response to intracerebroventricular hypertonic saline (0.6 M NaCl in CSF at 1 ml/h) was examined as there is evidence that hypertonic saline acts via angiotensinergic pathways. Intracerebroventricular angiotensin increased CSNA by 23 ± 7% ( P < 0.001) and mean arterial pressure (MAP) by 7.6 ± 1.2 mmHg ( P < 0.001) but did not significantly change heart rate ( n = 5). During intracerebroventricular ANG II the reflex relation between CSNA and diastolic blood pressure was significantly shifted to the right ( P < 0.01). Intracerebroventricular hypertonic saline increased CSNA (+9.4 ± 6.6%, P < 0.05) and MAP but did not alter heart rate. The responses to angiotensin and hypertonic saline were prevented by intracerebroventricular losartan (1 mg/h). In conclusion, in conscious sheep angiotensin acts within the brain to increase CSNA, despite increased MAP. The increase in CSNA may account partly for the lack of bradycardia in response to the increased arterial pressure. The responses to angiotensin and hypertonic saline were losartan sensitive, indicating they were mediated by angiotensin AT-1 receptors.

scholarly journals Adrenomedullin increases cardiac sympathetic nerve activity in normal conscious sheep

2005 ◽  
Vol 187 (2) ◽  
pp. 275-281 ◽  
Author(s):  
C J Charles ◽  
D L Jardine ◽  
M G Nicholls ◽  
A M Richards
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Vehicle Control ◽  
Cardiac Sympathetic Nerve ◽  
Burst Frequency ◽  
Nerve Activity ◽  
Cardiac Sympathetic Nerve Activity ◽  
Conscious Sheep

The sympathetic nervous system and adrenomedullin (AM) both participate in the regulation of cardiac and circulatory function but their interaction remains uncertain. We have examined the effects of AM on cardiac sympathetic nerve activity (CSNA) and hemodynamics and contrasted these effects with pressure-matched nitro-prusside (NP) administration in normal conscious sheep. Compared with vehicle control, arterial pressure fell similarly with AM (P=0.04) and NP (P<0.001). Heart rate rose in response to both AM (P<0.001) and NP (P=0.002) but the rise with AM was significantly greater than that induced by NP (P<0.001). Cardiac output increased in response to AM compared with both control and NP (both P<0.001). CSNA burst frequency (bursts/min) were increased in response to both AM (P<0.001) and NP (P=0.005) with the rise in burst frequency being greater with AM compared with NP (P<0.001). CSNA burst area/min was also raised by both AM (P=0.03) and NP (P=0.002) with a trend for burst area being greater with AM than NP (P=0.07). CSNA burst incidence (bursts/100 beats) showed no significant differences between any treatment day. In conclusion, we have demonstrated that AM is associated with a greater increase in CSNA and heart rate for a given change in arterial pressure than seen with the classic balanced vasodilator NP.

scholarly journals Systemic angiotensin II does not increase cardiac sympathetic nerve activity in normal conscious sheep

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Christopher J. Charles ◽  
David L. Jardine ◽  
Miriam T. Rademaker ◽  
A. Mark Richards
Keyword(s):  
Angiotensin Ii ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nervous Activity ◽  
Plasma Catecholamines ◽  
Ang Ii ◽  
Cardiac Sympathetic Nerve ◽  
Nerve Activity ◽  
Cardiac Sympathetic Nerve Activity ◽  
Conscious Sheep

While it is well established that centrally injected angiotensin II (Ang II) has potent actions on sympathetic nervous activity (SNA), it is less clear whether peripheral Ang II can immediately stimulate SNA. In particular, the contribution of cardiac sympathetic nerve activity (CSNA) to the acute pressor response is unknown. We therefore examined the effect of incremental doses of intravenous Ang II (3, 6, 12, 24, and 48 ng/kg/min each for 30 min) on CSNA in eight conscious sheep. Ang II infusions progressively increased plasma Ang II up to 50 pmol/l above control levels in dose-dependent fashion (P<0.001). This was associated with the expected increases in mean arterial pressure (MAP) above control levels from <10 mmHg at lower doses up to 23 mmHg at the highest dose (P<0.001). Heart rate and cardiac output fell progressively with each incremental Ang II infusion achieving significance at higher doses (P<0.001). There was no significant change in plasma catecholamines. At no dose did Ang II increase any of the CSNA parameters measured. Rather, CSNA burst frequency (P<0.001), burst incidence, (P=0.002), and burst area (P=0.004) progressively decreased achieving significance during the three highest doses. In conclusion, Ang II infused at physiologically relevant doses increased MAP in association with a reciprocal decrease in CSNA presumably via baroreceptor-mediated pathways. The present study provides no evidence that even low-dose systemic Ang II stimulates sympathetic traffic directed to the heart, in normal conscious sheep.

Continual recordings of cardiac sympathetic nerve activity in conscious sheep

2002 ◽  
Vol 282 (1) ◽  
pp. H93-H99 ◽  
Author(s):  
David L. Jardine ◽  
Christopher J. Charles ◽  
Ian C. Melton ◽  
Clive N. May ◽  
Melanie D. Forrester ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cardiac Disease ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Low Frequency ◽  
Cardiac Sympathetic Nerve ◽  
Nerve Activity ◽  
Recording Time ◽  
Cardiac Sympathetic Nerve Activity ◽  
Conscious Sheep

Cardiac sympathetic nerve activity (CSNA) is of major importance in the etiology of heart disease but is impossible to measure directly in humans. Ovine and human cardiovascular systems are similar; therefore, we have developed a method for the daily recording of CSNA in conscious sheep. After thoracotomy, electrodes were glued into the left thoracic cardiac nerve and CSNA, blood pressure (BP), and heart rate were recorded daily. Satisfactory recordings ≥7 days of CSNA were obtained in 11 of 28 sheep (40%), mean recording time 10.6 days, range 7-47. During the first week, CSNA decreased gradually from 78 ± 8 at baseline to 60 ± 7 bursts/min on day 5( P = 0.02) or from 76 ± 9 to 57 ± 7 bursts/100 beats on day 7 ( P = 0.04). Similarly, BP decreased from 103 ± 4 to 94 ± 4 mmHg ( P = 0.03). Low-frequency heart rate variability decreased from 0.12 ± 0.02 to 0.06 ± 0.02 ms2on day 6 ( P = 0.004) but was not correlated to CSNA. In conclusion, CSNA that can be continually recorded in conscious sheep decreases during the first week postsurgery and, thereafter, stabilizes. This model should provide valuable insights in future investigations of cardiac disease.

scholarly journals Mechanisms underlying the increased cardiac norepinephrine spillover in heart failure

2018 ◽  
Vol 315 (2) ◽  
pp. H340-H347 ◽  
Author(s):  
Rohit Ramchandra ◽  
Sally G. Hood ◽  
Daniel Xing ◽  
Gavin W. Lambert ◽  
Clive N. May
Keyword(s):  
Heart Failure ◽  
Arterial Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Cardiac Sympathetic Nerve ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
Cardiac Sympathetic Nerve Activity ◽  
Conscious Sheep ◽  
High Level

Patients with heart failure (HF) have increased levels of cardiac norepinephrine (NE) spillover, which is an independent predictor of mortality. We hypothesized that this increase in NE spillover in HF depends not only on increases in sympathetic nerve activity (SNA) but also on changes in the mechanisms controlling NE release and reuptake. Such changes would lead to differences between the increases in directly recorded SNA and NE spillover to the heart in HF. Experiments were conducted in conscious sheep implanted with electrodes to record cardiac SNA (CSNA). In addition, arterial pressure and cardiac NE spillover were determined. In HF, the levels of both CSNA (102 ± 8 vs. 45 ± 8 bursts/min, P < 0.05) and cardiac NE spillover (21.6 ± 3.8 vs. 3.9 ± 0.8 pmol/min, P < 0.05) were significantly higher than in normal control animals. In HF, baroreflex control of cardiac NE spillover was impaired, and when CSNA was abolished by increasing arterial pressure, there was no reduction in cardiac NE spillover. A decrease in cardiac filling pressures in the HF group led to a significant increase in CSNA, but it significantly decreased cardiac NE spillover. In HF, the levels of cardiac NE spillover were enhanced above those expected from the high level of SNA, suggesting that changes in mechanisms controlling NE release and reuptake further increase the high level of NE at the heart, which will act to enhance the deleterious effects of increased CSNA in HF. NEW & NOTEWORTHY This is the first study, to our knowledge, to compare direct recordings of cardiac sympathetic nerve activity with simultaneously measured cardiac norepinephrine (NE) spillover. Our results indicate that in heart failure, increased cardiac sympathetic nerve activity is a major contributor to the increased NE spillover. In addition, there is enhanced NE spillover for the levels of synaptic nerve activity.

Changes in AdSNA and arterial catecholamines to coronary occlusion in cats

1988 ◽  
Vol 255 (4) ◽  
pp. H704-H710 ◽  
Author(s):  
T. Honda ◽  
I. Ninomiya
Keyword(s):  
Heart Rate ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Coronary Occlusion ◽  
The Other ◽  
Cardiac Sympathetic Nerve ◽  
Nerve Activity ◽  
Control Value ◽  
Cardiac Sympathetic Nerve Activity ◽  
The Relationship

The relationship between adrenal (preganglionic) sympathetic nerve activity (AdSNA), cardiac sympathetic nerve activity (CSNA), and arterial catecholamines, i.e., epinephrine (Epi) and norepinephrine (NE), were analyzed during 200 s of occlusion of left anterior descending coronary artery in anesthetized cats. With coronary occlusion, AdSNA maximally increased to 168 +/- 20% (mean +/- SE) of the control value at 20 s and gradually decreased to 149 +/- 10% at 200 s. Mean CSNA (MCSNA), mean arterial pressure, and heart rate decreased significantly because of coronary occlusion. Arterial NE and Epi progressively increased from 0.54 +/- 0.05 and 0.29 +/- 0.03 ng/ml to 1.41 +/- 0.16 and 0.59 +/- 0.08 ng/ml at 3 min after the onset of occlusion, respectively. The correlation between AdSNA and arterial Epi (r = 0.71; P less than 0.01) and between AdSNA and arterial NE (r = 0.57; P less than 0.05) were significant, but the correlation between CSNA and arterial NE was not significant. On the other hand, in adrenalectomized cats, the increases in arterial Epi and NE did not appear during coronary occlusion. We concluded that, with coronary occlusion, AdSNA increased and, in turn, caused an increase in arterial Epi and NE.

Low-dose B-type natriuretic peptide raises cardiac sympathetic nerve activity in sheep

2014 ◽  
Vol 307 (2) ◽  
pp. R206-R211 ◽  
Author(s):  
Christopher J. Charles ◽  
David L. Jardine ◽  
Miriam T. Rademaker ◽  
A. Mark Richards
Keyword(s):  
Heart Rate ◽  
Natriuretic Peptide ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Low Dose ◽  
Statistical Significance ◽  
Burst Frequency ◽  
Nerve Activity ◽  
Cardiac Sympathetic Nerve Activity ◽  
Conscious Sheep

The reported effects of atrial natriuretic peptide (ANP) on sympathetic nerve activity (SNA) are variable, dependent on concomitant hemodynamic actions, and likely to be regionally differentiated. There are few reports of the effect of B-type natriuretic peptide (BNP) on SNA and none have measured cardiac SNA (CSNA) by direct microneurography. We measured the effects of low-dose ANP and BNP (2.4 pmol·kg−1·min−1 infused for 120 min) on CSNA and hemodynamics in conscious sheep ( n = 8). While there was a trend for mean arterial pressure and cardiac output to fall with both ANP and BNP, changes were not significant compared with vehicle control. However, BNP did significantly reduce systolic arterial (97 ± 4.2 vs. 107 ± 6.8 mmHg during control; P = 0.043) and pulse pressures (0.047) and increase heart rate (110 ± 6.7 vs. 96 ± 7.3 beats/min; P = 0.044). Trends for these hemodynamic parameters to change with ANP did not achieve statistical significance. ANP also had no significant effect on any CSNA parameters measured. In contrast, BNP induced a rise in both CSNA burst frequency (∼20 bursts/min higher than control, P = 0.011) and burst area (∼40% higher than control, P = 0.013). BNP-induced rises in burst incidence (bursts/100 beats), and burst area per 100 beats, however, were not significant. In conclusion, BNP infused at low doses that only had subtle effects on hemodynamics increased CSNA burst frequency and burst are per minute. This increase in CSNA may in large part be secondary to an increase in heart rate as CSNA burst incidence and burst area per 100 beats were not significantly increased. This study provides no evidence for inhibition of CSNA by natriuretic peptides.

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