Increased sympathetic venoconstriction and reactivity to norepinephrine in mesenteric veins in anesthetized DOCA-salt hypertensive rats

2007 ◽  
Vol 293 (1) ◽  
pp. H160-H168 ◽  
Author(s):  
Hui Xu ◽  
Gregory D. Fink ◽  
James J. Galligan
Keyword(s):  
Nervous Activity ◽  
Mesenteric Arteries ◽  
Sympathetic Nervous Activity ◽  
Response Curves ◽  
Mesenteric Veins ◽  
Salt Hypertension ◽  
Sympathetic Nervous ◽  
Venomotor Tone

Increased sympathetic nervous activity (SNA) elevates venomotor tone in deoxycorticosterone acetate (DOCA)-salt hypertension. We studied the mechanisms by which the SNA increases venomotor tone in DOCA-salt hypertension by making in situ intracellular recordings of venous smooth muscle cell (VSMC) membrane potential ( Em) and measurement of outside diameter (OD) in mesenteric veins (MV) and mesenteric arteries (MA) of anesthetized rats. We also studied norepinephrine (NE)- and endothelin-1 (ET-1)-induced increases in MA or MV perfusion pressure (PP) in vitro. Em in DOCA-salt MV was depolarized compared with sham MV. Prazosin hyperpolarized VSMC Em in DOCA-salt but not in sham MV. NE concentration-response curves (CRCs) for OD decreases in MV from DOCA-salt rats were left-shifted with an increased maximum response ( Emax) compared with sham MV. NE CRCs for OD decreases in MA were right-shifted with reduced Emax in DOCA-salt compared with sham rats. ET-1 CRCs were similar in DOCA-salt and sham MV but were right-shifted with reduced Emax in DOCA-salt MA. NE CRCs for MAPP increases were left-shifted without a change in Emax in DOCA-salt rats. NE did not change MVPP. MAPP and MVPP for ET-1 CRCs were similar in sham and DOCA-salt rats, but Emax for MAPP was reduced in DOCA-salt rats. Hematoxylin staining revealed hypertrophy in DOCA-salt MA but not in MV. We conclude that there is increased reactivity to NE released from the sympathetic nervous system in DOCA-salt MV that causes VSMC depolarization and increased venomotor tone. In DOCA-salt rats, in vivo ET-1 reactivity is maintained in MV, but reduced in MA.

Enhancement by vasopressin of adrenergic responses in human mesenteric arteries

1997 ◽  
Vol 272 (3) ◽  
pp. H1087-H1093 ◽  
Author(s):  
P. Medina ◽  
I. Noguera ◽  
M. Aldasoro ◽  
J. M. Vila ◽  
B. Flor ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Animal Experiments ◽  
Mesenteric Arteries ◽  
Organ Bath ◽  
Adrenergic Stimulation ◽  
Response Curves ◽  
Receptor Stimulation ◽  
Half Maximal Effective Concentration

Vasopressin not only acts directly on blood vessels through V1-receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments in vitro and in vivo. The aim of the present study was to investigate whether subpressor concentrations of vasopressin could modify the constrictor responses to norepinephrine and electrical stimulation of the perivascular nerves in human mesenteric arteries. Human mesenteric artery rings (3-3.5 mm long, 0.8-1.2 mm OD) were obtained from 38 patients undergoing abdominal operations. The arterial rings were suspended in organ bath chambers for isometric recording of tension. Vasopressin (3 x 10(-11) M) enhanced the contractions elicited by electrical stimulation at 2, 4, and 8 Hz (by 100, 100, and 72%, respectively) and produced a leftward shift of the concentration-response curves to norepinephrine (half-maximal effective concentration decreased from 2.2 x 10(-6) to 5.0 x 10(-7) M; P < 0.05) without any alteration in maximal contractions. Vasopressin also potentiated KCl- and calcium-induced contractions. The V1-receptor antagonist 1-[beta-mercapto-beta,beta-cyclopentamethylenepropionic acid-2-O-methyl-tyrosine, 8-arginine]vasopressin (10(-6) M) prevented the potentiation evoked by vasopressin in all cases. The calcium antagonist nifedipine (10(-6) M) did not affect the potentiation of electrical stimulation and norepinephrine induced by vasopressin but abolished KCl-induced contractions. The results suggest that vasopressin, in addition to its direct vasoconstrictor effect, strongly potentiates the responses to adrenergic stimulation and KCl depolarization. Both the direct and indirect effects of vasopressin appear to be mediated by V1-receptor stimulation. The amplifying effect of vasopressin on constrictor responses may be relevant in those clinical situations characterized by increased plasma vasopressin levels.

Abstract P304: A Sympathetic-cholinergic Pathway Performs a Connection Between Brain and Spleen, to Prime Immune System and Induce Arterial Hypertension

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Daniela Carnevale ◽  
Marialuisa Perrotta ◽  
Fabio Pallante ◽  
Lorenzo Carnevale ◽  
Giuseppe Cifelli ◽  
...  
Keyword(s):  
Immune System ◽  
Nervous Activity ◽  
Firing Frequency ◽  
Sympathetic Nervous Activity ◽  
Immune System Activation ◽  
Cholinergic Pathway ◽  
Sympathetic Nervous ◽  
The Brain ◽  
Sympathetic Pathway

It is now widely recognized that immune system has a crucial role in hypertension. Various studies have demonstrated that the activation of adaptive immunity, and in particular of T cells, is a crucial moment in the onset and maintaining of hypertension induced by various stimuli in mice. Our previous studies have shown that hypertensive stimuli couple the sympathetic nervous system to determine the activation of splenic immune system. However, how the brain-to-spleen connection is realized in hypertension remains unknown. In this study we demonstrate that mice subjected to various hypertensive stimuli (AngII, DOCA-salt) show an increase of sympathetic nervous activity recorded in vivo in the splenic nerve (Firing Frequency: AngII 131±17 vs Veh 30±10 spikes/10 min, p<0.001). We also show how the sympathetic pathway induced by pro-hypertensive stimuli has its origin in the brain, converging into the spleen through a cholinergic-sympathetic connection that is realized through the vagus-splenic nerve drive and mediated at the molecular level by cholinergic nicotinic receptors at the level of celiac ganglion. In fact, we show that in celiac vagotomized mice, i.e. mice subjected to a procedure inhibiting vagal efferents but not central afferents, the splenic nervous drive induced by AngII was absent (AngII+VagX 21±4 vs AngII+sham 148±29 spikes/10 min, p<0.001). The same result was shown in α7 cholinergic nicotinic receptor KO mice, a receptor typically expressed by neurons in the peripheral ganglia (α7nAChR KO AngII 43±8 vs WT AngII 141±27 spikes/10 min, p<0.01). Moreover, we found that this cholinergic-sympathetic pathway was necessary to allow the activation of T cell costimulation and egression upon hypertensive challenges. Our results highlight a cholinergic-sympathetic pathway played by vagus-splenic nerves and responsible for immune system activation in response to hypertensive stimuli. We believe our results are significant because they reveal a previously unknown sympathetic pathway in hypertension for the first time. The brain-to-spleen connection realized through a cholinergic-sympathetic nervous drive that resembles the cholinergic anti-inflammatory pathway identified by immunologists in endotoxemia.

Sympathetic nervous activity in carriers of MC4R mutations

2006 ◽  
Vol 114 (S 1) ◽  
Author(s):  
D Heutling ◽  
F Sayk ◽  
C Dodt ◽  
HL Fehm ◽  
A Hinney ◽  
...  
Keyword(s):  
Nervous Activity ◽  
Sympathetic Nervous Activity ◽  
Sympathetic Nervous

Sympathetic nervous activity in patients with chronic renal failure

1994 ◽  
Vol 1 ◽  
pp. 314
Author(s):  
E. Gotoh ◽  
T. Matsukawa ◽  
S. Sumita ◽  
K. Ashino ◽  
N. Takagi ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Nervous Activity ◽  
Sympathetic Nervous Activity ◽  
Sympathetic Nervous

4-Chloro-m-cresol Triggers Malignant Hyperthermia in Susceptible Swine at Doses Greatly Exceeding Those Found in Drug Preparations

1999 ◽  
Vol 90 (6) ◽  
pp. 1723-1732. ◽  
Author(s):  
Paul A. Iaizzo ◽  
Brooks A. Johnson ◽  
Kaoru Nagao ◽  
William J. Gallagher
Keyword(s):  
Malignant Hyperthermia ◽  
Blood Chemistry ◽  
Response Curves ◽  
End Tidal ◽  
In Vivo Effects ◽  
Higher Doses ◽  
End Tidal Co2 ◽  
Cardiovascular Reactions

Background Chlorocresols are used as preservatives in numerous commercial drugs that have been shown to induce myoplasmic Ca2+ release; the most potent isoform is 4-chloro-m-cresol. The aims of this study were to (1) examine the in vivo effects of 4-chloro-m-cresol on swine susceptible to malignant hyperthermia and (2) contrast in vivo versus in vitro dose-response curves. Methods Susceptible swine (weight: 38.5 kg+/-3.55 kg) were anesthetized and monitored for variations in physiological responses, including end-tidal CO2, heart rate, blood pressure, blood chemistry, and temperatures. In the first animals studied, 4-chloro-m-cresol, at equivalent cumulative doses of 0.14, 0.28, 0.57, 1.14, 2.27, 4.54, and 9.08 mg/kg (n = 3; 12.5, 25, 50, 100, 200, 400, and 800 micromol) were administered, and in a second group, larger doses were used: 1.14, 3.41, 7.95, 17.04 (n = 4), and/or 35.22 (n = 1) mg/kg (100, 300, 700, 1,500, and/or 3,100 micromol). For comparison, in vitro rectus abdominis muscle preparations obtained from normal and susceptible swine were exposed to 4-chloro-m-cresol, at cumulative concentrations of 6.25, 12.5, 25, 50, 100, 200, 400, 800, and 1,600 micromol; standard caffeine and halothane contracture testing was also performed. Results Episodes of malignant hyperthermia were not triggered in response to administration of low doses of 4-chloro-m-cresol, but transient cardiovascular reactions (e.g., tachycardia, arrhythmias, and hypotension) were observed. Subsequently, episodes in these animals were triggered when halothane (0.87; 1 MAC) and succinylcholine (2 mg/kg) were given. Animals administered the higher doses of 4-chloro-m-cresol all had fulminant episodes of malignant hyperthermia that were fatal, when equivalent cumulative concentrations were greater than 1,500 micromol. The levels of 4-chloro-m-cresol in the plasma rapidly decreased: e.g., 5 min postadministration of the 1,500-micromol dose, the mean plasma level was only 52+/-18 micromol (n = 4). Hemolysis was detected following 4-chloro-m-cresol administration at concentrations &gt; 200 micromol. In vitro, muscle from susceptible animals elicited contractures &gt; 200 mg at 50-micromol bath concentrations of 4-chloro-m-cresol (n = 29), whereas normal muscle did not elicit such contractures until bath concentrations were &gt; 800 micromol (n = 10). Conclusions 4-chloro-m-cresol is a trigger of malignant hyperthermia in susceptible swine, but only when serum concentrations are far above those likely to be encountered in humans. A relatively low concentration of 4-chloro-m-cresol, 50 micromol, is sufficient to activate sarcoplasmic [Ca+2] release in vitro (e.g., contractures); this same bolus dose administered in vivo (0.57 mg/kg) has minimal effects due to the rapid decrease in its plasma levels.

Variations in Individual Organ Release of Noradrenaline Measured by An Improved Radioenzymatic Technique; Limitations of Peripheral Venous Measurements in the Assessment of Sympathetic Nervous Activity

1981 ◽  
Vol 61 (5) ◽  
pp. 585-590 ◽  
Author(s):  
M. J. Brown ◽  
D. A. Jenner ◽  
D. J. Allison ◽  
C. T. Dollery
Keyword(s):  
Renal Artery ◽  
Renal Artery Stenosis ◽  
Nervous Activity ◽  
Artery Stenosis ◽  
Plasma Noradrenaline ◽  
Sympathetic Nervous Activity ◽  
Release Of Noradrenaline ◽  
Noradrenaline Concentration ◽  
Sympathetic Nervous ◽  
Noradrenaline And Adrenaline

1. The validity of plasma noradrenaline as an index of sympathetic nervous activity was assessed by estimating variation in individual organ contribution to circulating concentrations. 2. Arteriovenous (A—V) differences in noradrenaline and adrenaline concentration were measured across several organs in nine patients with mild essential hypertension, in five with renal artery stenosis and 15 phaeochromocytoma patients. 3. In patients with phaeochromocytomas the percentage extraction of noradrenaline and adrenaline (estimated from the A—V differences) was similar across all organs, suggesting that adrenaline extraction could be used as a marker for noradrenaline extraction. 4. In the non-tumour patients the A—V difference for noradrenaline was less than that for adrenaline across most organs studied, reflecting the net result of noradrenaline release and extraction. The estimated contribution of various organs to the noradrenaline concentrations in their venous effluent was: heart. 21%; kidney 47%; legs 68%. 5. This pattern of A—V difference proved a positive diagnostic feature for non-tumour patients since it was not found even in the patients with small phaeochromocytomas, whose peripheral venous noradrenaline concentration alone did not distinguish them. 6. The venous-arterial difference across the adrenal glands of non-tumour patients was more than 10-fold greater for adrenaline than that for noradrenaline. Since the mean arterial concentration of noradrenaline was more than fivefold higher than that of adrenaline, the normal adrenal contribution to circulating noradrenaline is likely to be less than 2%. 7. In the patients with renal artery stenosis renal venous concentrations of noradrenaline (from the ischaemic kidney) were higher than arterial values, but mean arterial values were no higher than in the essential hypertensive patients. 8. Local variations in sympathetic activity may occur without altering the plasma noradrenaline concentration measured in peripheral plasma.

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