Nitric oxide (NO) donors inhibit sympathetic neurotransmission and baroreceptor activity and can directly stimulate heart rate (HR) in vitro. To assess whether exogenous NO affects cardiovascular autonomic control in humans, we tested the baroreceptor-cardiac reflex [baroreflex sensitivity (BRS)] and the arterial blood pressure (BP) and HR variability during an infusion of the NO donor sodium nitroprusside (SNP, 2 μg ⋅ kg −1 ⋅ min −1 ) or 5% glucose in 16 healthy subjects. The hypotensive action of SNP was prevented by phenylephrine (PE, 0.9 ± 0.15 μg ⋅ kg −1 ⋅ min −1 ). The SNP + PE infusion did not affect BRS or HR variability, but it caused a significant reduction in the diastolic and systolic BP low-frequency power. In addition, SNP + PE caused a sustained 12% increase in HR in the absence of changes in brachial and aortic BP. In conclusion, SNP had no effect on the cardiac-vagal limb of the baroreflex in humans but caused a substantial reduction in BP low-frequency power consistent with a decreased baroreflex/sympathetic control of peripheral resistance. The increase in HR in the absence of baroreceptor downloading confirms our previous finding of a direct positive chronotropic effect of NO donors.

10.1152/ajpheart.1999.277.1.h221

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Citations (39)

Effect of verapamil on restoration of cardiac performance in raised [K⁺]₀ by adrenergic stimulation in the rabbit

Acta Physiologica Scandinavica (1995)

M. O.' NEILL Daisy Ryan David J. Paterson

Modulation of the L‐type calcium channel by catecholamines improves action potential parameters in single ventricular myocytes depolarized by high [K + ] 0 Tyrode. Whether this modulation is important in offsetting the negative effects of hyperkalaemia in the whole heart is not known. We tested the effects of the calcium channel antagonist, verapamil, on restoration of cardiac performance by adrenergic stimulation in high [K + ] 0 in anaesthetized rabbits and isolated perfused working rabbit hearts. Raised [K + ] 0 decreased SBP, LVP and LVdP/dt max in vivo ([K + ] a 8.6 ± 0.2 mM; n = 10) and aortic flow (AF) in the isolated heart (8 mM [K + ] 0 Tyrode; n = 25). However, the negative effects of raised [K + ] a were offset by isoprenaline (Iso, 1 μg kg ‐1 min ‐1 i.v.) in vivo and by noradrenaline (NA, 80 nM) in the isolated heart. Verapamil (0.15 mg kg ‐1 iv.; 15 nM isolated heart) markedly potentiated the negative inotropic effects of raised [K + ] n in both preparations. Verapamil attenuated the effect of isoprenaline in vivo but in the isolated heart, the protective effect of NA in 8 mM [K + ] Tyrode (AF 97 ± 10 mL min 1 in 8 mM [K + ] 0 compared with AF 141 ± 8.5 mL min ‐1 in 8 mM [K + ] 0 + NA) was offset by the drug (90±8mL min ‐1 in 8 mM [K + ] 0 + NA + V). Furthermore, verapamil abolished aortic flow in 8 mM [K + ] 0 alone. These findings suggest that the heart may be critically dependent on modulation of intracellular calcium in order to tolerate concentrations of K 4 similar to those seen during a short burst of intensive exercise ([K + ] a 8.6 mM).

Rabbit (cipher)

10.1111/j.1748-1716.1995.tb09920.x

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Citations (1)

THE EFFECT OF HYPOXIA ON PLASMA POTASSIUM CONCENTRATION AND THE EXCITATION OF ARTERIAL CHEMORECEPTORS IN THE CAT

Quarterly Journal of Experimental Physiology (1988)

David J. Paterson P. C. G. Nye Jaime A. Estavillo

Intra‐arterial recordings of potassium concentration ([K + ] a ) and arterial chemoreceptor discharge were made in six anaesthetized cats while tracheal P O2 was stepped every 2 min (end‐tidal P O2 ca . 140, 60, 40 and 95 Torr) at constant PCO2 (33 Torr). [K+]a increased hyperbolically from 3·0 mM to 4·5 mM as arterial P O2 was lowered from 95 to 40 Torr. Because the discharge of arterial chemoreceptors is excited by hyperkalaemia as well as hypoxia, the hypoxic discharge of arterial chemoreceptors may have a component mediated by [K + ] a . The mechanisms underlying the arterial K + increase in hypoxia remain unknown.

Hypoxia

10.1113/expphysiol.1988.sp003182

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Citations (16)

Effect of Deep Brain Stimulation on Sympathetic outflow in humans

Autonomic Neuroscience (2015)

Yrsa Bergmann Sverrisdóttir A.L. Green Tipu Z. Aziz Nor Faizal Ahmad Bahuri Jonny A. Hyam

Vasomotor

Rostral ventrolateral medulla

Periaqueductal gray

Sympathetic nervous system

10.1016/j.autneu.2015.07.403

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Citations (1)

Exercise-induced hyperkalemia and concentration of Na,K-pumps in skeletal muscle in mitral stenosis: effect of balloon mitral valvotomy.

PubMed (1999)

Clifford W. Barlow Jeremy Long Pravin Manga Theo E. Meyer David J. Paterson

The study aim was to examine the effects of balloon mitral valvotomy (BMV) on exercise-induced hyperkalemia, and on changes in the concentration of Na,K-pumps in skeletal muscle, as an exaggerated exercise-induced rise in potassium concentration ([K+]) may contribute to exertional fatigue and breathlessness.Eight subjects were evaluated with mitral stenosis (mean age 34 +/- 5.2 years) before, and at two weeks and four months after BMV. Subjects underwent incremental exercise to exhaustion for exercise-induced rise in [K+] and vastus lateralis biopsy for concentration of Na,K-pumps.Mean (+/- SE) valve area increased from 0.89 +/- 0.03 cm2 before to 1.75 +/- 0.05 cm2 after BMV. There was a progressive increase in VO2,max (15.3 +/- 1.6, 17.2 +/- 1.4 and 19.9 +/- 1.9 l/kg/min) at baseline, early after and later after BMV, respectively (p < 0.01). The rise in [K+] with absolute workload fell progressively at early and late follow up post-BMV (p < 0.05), but was unchanged when plotted against percentage of VO2,max to match for relative workload. The concentration of Na,K-pumps was similar to baseline at early follow up (233 +/- 10 versus 228 +/- 15 pmol/g wet weight), but was significantly increased at late follow up after four months (265 +/- 17 pmol/g; p < 0.05). When the relationship between the concentration of Na,K-pumps and the exercise-induced rise in [K+] was studied, a negative correlation was found. However, correlation analysis for the effects of changes in Na,K-pumps on changes in exercise hyperkalemia after BMV was not significant.The progressive reduction in exercise-induced rise in [K+] after BMV may contribute to the progressive improvement in exercise performance. The increased concentration of Na,K-pumps in skeletal muscle may assist in this improvement, and emphasizes the importance of peripheral adaptations in clinical improvement after BMV.

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C-type natriuretic peptide and natriuretic peptide receptor B signalling inhibits cardiac sympathetic neurotransmission and autonomic function

Cardiovascular Research (2016)

Jens Buttgereit Julia Shanks Dan Li Guoliang Hao Arvinder Athwal

AimsB-type natriuretic peptide (BNP)-natriuretic peptide receptor A (NPR-A) receptor signalling inhibits cardiac sympathetic neurotransmission, although C-type natriuretic peptide (CNP) is the predominant neuropeptide of the nervous system with expression in the heart and vasculature.We hypothesized that CNP acts similarly to BNP, and that transgenic rats (TGRs) with neuron-specific overexpression of a dominant negative NPR-B receptor would develop heightened sympathetic drive.........

NPR2

NPR1

Sympathetic nervous system

10.1093/cvr/cvw184

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Citations (34)

Ventral periaqueductal grey stimulation alters heart rate variability in humans with chronic pain

Experimental Neurology (2010)

Erlick A.C. Pereira Guohua Lü Shouyan Wang Patrick Schweder Jonathan A. Hyam

Periaqueductal gray

10.1016/j.expneurol.2010.02.004

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Citations (100)

Impaired regulation of neuronal nitric oxide synthase during exercise abolishes training-induced facilitation of cardiac vagal function in mice lacking one nNOS allele

Circulation (2003)

E. Danson Kulveer Mankia Shijie Cai S Golding Keith M. Channon

Facilitation

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FRET-based cyclic GMP biosensors measure low cGMP concentrations in cardiomyocytes and neurons

Communications Biology (2019)

Gaia Calamera Dan Li Andrea Hembre Ulsund Jeong Joo Kim Oliver C. Neely

Abstract Several FRET (fluorescence resonance energy transfer)-based biosensors for intracellular detection of cyclic nucleotides have been designed in the past decade. However, few such biosensors are available for cGMP, and even fewer that detect low nanomolar cGMP concentrations. Our aim was to develop a FRET-based cGMP biosensor with high affinity for cGMP as a tool for intracellular signaling studies. We used the carboxyl-terminal cyclic nucleotide binding domain of Plasmodium falciparum cGMP-dependent protein kinase (PKG) flanked by different FRET pairs to generate two cGMP biosensors (Yellow Pf PKG and Red Pf PKG). Here, we report that these cGMP biosensors display high affinity for cGMP (EC 50 of 23 ± 3 nM) and detect cGMP produced through soluble guanylyl cyclase and guanylyl cyclase A in stellate ganglion neurons and guanylyl cyclase B in cardiomyocytes. These biosensors are therefore optimal tools for real-time measurements of low concentrations of cGMP in living cells.

10.1038/s42003-019-0641-x

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Citations (35)