Tonic arterial chemoreceptor activity contributes to cardiac, but not renal, sympathetic activation in heart failure (1169.2)

Experiments were performed to test the postulate that neural influences underlie the suppressed excretory response to acute volume expansion (VE) typically observed 3-4 wk after myocardial infarction to induce chronic heart failure (CHF). Responses to VE were assessed in innervated (intact) and denervated (DNX) kidneys of anesthetized CHF rats and sham-operated controls. CHF rats exhibited blunted natriuretic responses to VE in both intact kidneys (35% of sham response) and DNX kidneys (55% of sham DNX response). CHF rats also displayed suppressed excretory responses to atrial natriuretic factor (0.25 microgram.kg-1.min-1 iv) in both intact kidneys (74% of sham response) and DNX kidneys (63% of sham DNX response). Additional experiments confirmed that the compliance of the venoatrial junction did not differ between sham rats (52 +/- 2 mmHg/microliter) and CHF rats (54-2 mmHg/microliter). The observations support the contention that both tonic renal sympathetic renal nerve activity and suppressed renal atrial natriuretic factor responsiveness likely contribute to the blunted excretory response to VE during CHF.

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Angiotensin receptor antagonist improves cardiac reflex control of renal sodium handling in heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.274.2.h636 ◽

1998 ◽

Vol 274 (2) ◽

pp. H636-H641 ◽

Cited By ~ 21

Author(s):

Gerald F. Dibona ◽

Susan Y. Jones ◽

Linda L. Sawin

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Right Atrial ◽

Nerve Activity ◽

Renal Sympathetic Nerve Activity ◽

Renal Sympathetic Nerve ◽

Renal Sodium Handling ◽

Renal Sympathetic

In rats with congestive heart failure, type 1 angiotensin II receptor antagonist treatment (losartan) decreases basal renal sympathetic nerve activity and improves arterial baroreflex regulation of renal sympathetic nerve activity. This investigation examined the effect of losartan on cardiac baroreflex regulation of renal sympathetic nerve activity and renal sodium handling in rats with congestive heart failure. Losartan treatment decreased arterial pressure from 120 ± 3 to 93 ± 5 mmHg and increased the afferent (from 0.95 ± 0.21 to 2.22 ± 0.42% Δafferent vagal nerve activity/mmHg mean right atrial pressure, P < 0.05) and overall gain (from −1.14 ± 0.19 to −4.20 ± 0.39% Δrenal sympathetic nerve activity/mmHg mean right atrial pressure, P < 0.05) of the cardiac baroreflex. During isotonic saline volume loading, urinary sodium excretion increased from 2.4 ± 0.8 to 10.5 ± 1.3 μeq/min in vehicle-treated rats (excretion of 52 ± 3% of the load) and from 3.0 ± 1.0 to 15.1 ± 1.8 μeq/min in losartan-treated rats (excretion of 65 ± 4% of the load, P < 0.05). When rats were changed from a low- to a high-sodium diet, cumulative sodium balance over 5 days was 7.8 ± 0.6 meq in vehicle-treated rats and 4.2 ± 0.4 meq in losartan-treated rats ( P < 0.05). In congestive heart failure, losartan treatment improved cardiac baroreflex regulation of renal sympathetic nerve activity, which was associated with improved ability to excrete acute and chronic sodium loads.

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Downregulation of carbon monoxide as well as nitric oxide contributes to peripheral chemoreflex hypersensitivity in heart failure rabbits

Journal of Applied Physiology ◽

10.1152/japplphysiol.01345.2007 ◽

2008 ◽

Vol 105 (1) ◽

pp. 14-23 ◽

Cited By ~ 26

Author(s):

Yanfeng Ding ◽

Yu-Long Li ◽

Harold D. Schultz

Keyword(s):

Nitric Oxide ◽

Heart Failure ◽

Carbon Monoxide ◽

Sympathetic Nerve ◽

No Donor ◽

Renal Sympathetic Nerve ◽

Chemoreflex Sensitivity ◽

Tubulin Protein ◽

Peripheral Chemoreflex ◽

Renal Sympathetic

Peripheral chemoreflex sensitivity is potentiated in clinical and experimental chronic heart failure (CHF). Downregulation of nitric oxide (NO) synthase (NOS) in the carotid body (CB) is involved in this effect. However, it remains poorly understood whether carbon monoxide (CO) also contributes to the altered peripheral chemoreflex sensitivity in CHF. This work highlights the effect of NO and CO on renal sympathetic nerve activity (RSNA) in response to graded hypoxia in conscious rabbits. Renal sympathetic nerve responses to graded hypoxia were enhanced in CHF rabbits compared with sham rabbits. The NO donor S-nitroso- N-acetylpenicillamine (SNAP, 1.2 μg·kg−1·min−1) and the CO-releasing molecule tricarbonyldichlororuthenium (II) dimer {[Ru(CO)3Cl2]2, 3.0 μg·kg−1·min−1} each attenuated hypoxia-induced RSNA increases in CHF rabbits ( P < 0.05), but the degree of attenuation of RSNA induced by SNAP or [Ru(CO)3Cl2]2 was smaller than that induced by SNAP + [Ru(CO)3Cl2]2. Conversely, treatment with the NOS inhibitor Nω-nitro-l-arginine (30 mg/kg) + the heme oxygenase (HO) inhibitor Cr (III) mesoporphyrin IX chloride (0.5 mg/kg) augmented the renal sympathetic nerve response to hypoxia in sham rabbits to a greater extent than treatment with either inhibitor alone and was without effect in CHF rabbits. In addition, using immunostaining and Western blot analyses, we found that expression of neuronal NOS, endothelial NOS, and HO-2 protein (expressed as the ratio of NOS or HO-2 expression to β-tubulin protein expression) was lower in CBs from CHF (0.19 ± 0.04, 0.17 ± 0.06, and 0.15 ± 0.02, respectively) than sham (0.63 ± 0.04, 0.56 ± 0.06, and 0.27 ± 0.03, respectively) rabbits ( P < 0.05). These results suggest that a deficiency of NO and CO in the CBs augments peripheral chemoreflex sensitivity to hypoxia in CHF.

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Responses mediated by the RVLM on splancnic and renal sympathetic nerve activity in heart failure rats

The FASEB Journal ◽

10.1096/fasebj.20.4.a738-a ◽

2006 ◽

Vol 20 (4) ◽

Author(s):

Bruno Arruda Carillo ◽

Paulo J.F Tucci ◽

Ednei L Antonio ◽

Alexandra A Santos ◽

Cassia T Bergamaschi ◽

...

Keyword(s):

Heart Failure ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Nerve Activity ◽

Renal Sympathetic Nerve Activity ◽

Renal Sympathetic Nerve ◽

Renal Sympathetic

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The 2009 Carl Ludwig Lecture: pathophysiology of the human sympathetic nervous system in cardiovascular diseases: the transition from mechanisms to medical management

Journal of Applied Physiology ◽

10.1152/japplphysiol.00832.2009 ◽

2010 ◽

Vol 108 (2) ◽

pp. 227-237 ◽

Cited By ~ 162

Author(s):

Murray Esler

Keyword(s):

Heart Failure ◽

Nervous System ◽

Heart Disease ◽

Essential Hypertension ◽

Sympathetic Nervous System ◽

Clinical Translation ◽

Organ Specific ◽

Circulatory Control ◽

Sympathetic Nervous ◽

Renal Sympathetic

Sympathetic nervous system responses typically are regionally differentiated, with activation in one outflow sometimes accompanying no change or sympathetic inhibition in another. Regional sympathetic activity is best studied in humans by recording from postganglionic sympathetic efferents (multiunit or single fiber recording) and by isotope dilution-derived measurement of organ-specific norepinephrine release to plasma (regional “norepinephrine spillover”). Evidence assembled in this review indicates that sympathetic nervous system abnormalities are crucial in the development of cardiovascular disorders, notably heart failure, essential hypertension, disorders of postural circulatory control causing syncope, and “psychogenic heart disease,” heart disease attributable to mental stress and psychiatric illness. These abnormalities involve persistent, adverse activation of sympathetic outflows to the heart and kidneys in heart failure and hypertension, episodic or ongoing cardiac sympathetic activation in psychogenic heart disease, and defective sympathetic circulatory reflexes in disorders of postural circulatory control. An important goal for clinical scientists is translation of knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this “mechanisms-to-management” transition is at differing stages of development with the different conditions. Clinical translation is mature in cardiac failure, knowledge of cardiac neural pathophysiology having led to introduction of β-adrenergic blockers, an effective therapy. With essential hypertension, perhaps we are on the cusp of effective translation, with recent successful testing of selective catheter-based renal sympathetic nerve ablation in patients with resistant hypertension, an intervention firmly based on demonstration of activation of the renal sympathetic outflow. With psychogenic heart disease and postural syncope syndromes, knowledge of the neural pathophysiology is emerging, but clinical translation remains for the future.

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