Inhibition of neuronal noradrenaline uptake by angiotensin II in the rat mesentery

1979 ◽  
Vol 57 (12) ◽  
pp. 1443-1447 ◽  
Author(s):  
Edwin K. Jackson ◽  
William B. Campbell
Keyword(s):  
Angiotensin Ii ◽  
Extraneuronal Uptake ◽  
Neuronal Uptake ◽  
Appreciable Effect ◽  
Noradrenaline Uptake ◽  
Similar Extent ◽  
Rat Mesentery ◽  
Uptake Of Noradrenaline ◽  
6 Hydroxydopamine ◽  
Uptake Blockers

In the isolated perfused rat mesentery, angiotensin II (3 × 10−9 M) in subpressor doses enhanced the vasoconstrictor responses to noradrenaline by 9.6 ± 1.4 mmHg. However, in mesenteries obtained from rats chemically sympathectomized with 6-hydroxydopamine, angiotensin II was without effect. Treatment of mesenteries with the noradrenaline neuronal uptake blockers desmethylimipramine (10−10 M), protriptyline (10−10 M), or cocaine (10−6 M) potentiated responses to noradrenaline by 3.8 ± 0.84, 3.7 ± 0.67, and 5.5 ± 0.26 mmHg, respectively. Angiotensin II alone or in combination with either desmethylimipramine, protriptyline, or cocaine potentiated the noradrenaline responses to a similar extent. On the other hand, corticosterone (1.5 × 10−6 M), an extraneuronal uptake blocker, enhanced noradrenaline responses by 4.3 ± 1.4 mmHg, and this enhancement was additive with the potentiation produced by cocaine and (or) angiotensin II. We conclude that angiotensin II in subpressor doses acts presynaptically to block selectively the neuronal uptake of noradrenaline without any appreciable effect on extraneuronal uptake.

Determination of Noradrenaline Uptake, Spillover to Plasma and Plasma Concentration in Patients with Essential Hypertension

1980 ◽  
Vol 59 (s6) ◽  
pp. 311s-313s ◽  
Author(s):  
M. Esler ◽  
G. Jackman ◽  
P. Leonard ◽  
A. Bobik ◽  
Helen Skews ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Normal Subjects ◽  
Plasma Noradrenaline ◽  
Neuronal Uptake ◽  
Noradrenaline Uptake ◽  
Plasma Noradrenaline Concentration ◽  
Noradrenaline Concentration ◽  
Uptake Of Noradrenaline ◽  
Rapid Removal ◽  
Autonomic Insufficiency

1. The rates of entry of noradrenaline to plasma and of removal of noradrenaline from plasma, and plasma noradrenaline concentration, were determined in normal subjects and in patients with essential hypertension. Neuronal uptake of noradrenaline was assessed from the plasma tritiated noradrenaline disappearance curve, after infusion to steady state. 2. Noradrenaline disappearance was biexponential. Rapid removal was dependent on neuronal uptake, being slowed if neuronal noradrenaline uptake was reduced, either by desipramine in normal subjects, or in patients with sympathetic nerve dysfunction (autonomic insufficiency). 3. In 10 of 41 hypertensive patients the t1 1/2 similarly was prolonged, presumptive evidence of a defect in neuronal noradrenaline uptake. Endogenous noradrenaline escaping uptake after release, and spilling over into plasma, and plasma noradrenaline concentration, were increased in these patients. 4. Defective neuronal uptake of noradrenaline, by exposing adrenoreceptors to high local transmitter concentration, may be important in the pathogenesis of essential hypertension in some patients.

Norepinephrine uptake by rat jejunum: modulation by angiotensin II

1988 ◽  
Vol 254 (2) ◽  
pp. G135-G141 ◽  
Author(s):  
A. Suvannapura ◽  
N. R. Levens
Keyword(s):  
Small Intestine ◽  
Angiotensin Ii ◽  
Maximum Velocity ◽  
Sympathetic Nerves ◽  
Neuronal Uptake ◽  
Dependent Manner ◽  
Rat Jejunum ◽  
Ang Ii ◽  
Concentration Dependent Manner ◽  
6 Hydroxydopamine

Angiotensin II (ANG II) is believed to stimulate sodium and water absorption from the small intestine by enhancing sympathetic nerve transmission. This study is designed to determine whether ANG II can enhance sympathetic neurotransmission within the small intestine by inhibiting norepinephrine (NE) uptake. Intracellular NE accumulation by rat jejunum was concentration dependent and resolved into high- and low-affinity components. The high-affinity component (uptake 1) exhibited a Michaelis constant (Km) of 1.72 microM and a maximum velocity (Vmax) of 1.19 nmol.g-1.10 min-1. The low-affinity component (uptake 2) exhibited a Km of 111.1 microM and a Vmax of 37.1 nmol.g-1.10 min-1. Cocaine, an inhibitor of neuronal uptake, inhibited the intracellular accumulation of label by 80%. Treatment of animals with 6-hydroxydopamine, which depletes norepinephrine from sympathetic terminals, also attenuated NE uptake by 60%. Thus accumulation within sympathetic nerves constitutes the major form of [3H]NE uptake into rat jejunum. ANG II inhibited intracellular [3H]NE uptake in a concentration-dependent manner. At a dose of 1 mM, ANG II inhibited intracellular [3H]NE accumulation by 60%. Cocaine failed to potentiate the inhibition of [3H]NE uptake produced by ANG II. Thus ANG II appears to prevent [3H]NE accumulation within rat jejunum by inhibiting neuronal uptake.

Ketamine potentiates catecholamine responses of vascular smooth muscle by inhibition of extraneuronal uptake

1981 ◽  
Vol 59 (6) ◽  
pp. 520-527 ◽  
Author(s):  
Paul M. Lundy ◽  
Robert Frew
Keyword(s):  
Smooth Muscles ◽  
Rabbit Aorta ◽  
Extraneuronal Uptake ◽  
Neuronal Uptake ◽  
Vascular Smooth Muscles ◽  
Comt Inhibitors ◽  
Relaxant Effect ◽  
17Β Estradiol ◽  
Uptake Studies ◽  
6 Hydroxydopamine

Effects of ketamine on responses to sympathomimetic amines were studied using isolated aortic and pulmonary artery strips from the rabbit. Ketamine (1.1 × 10−5 to 3.7 × 10−4 M) potentiated adrenaline-contracted strips. Potentiation was not impaired in tissues from animals pretreated with reserpine, with 6-hydroxydopamine, or in tissues pretreated with cocaine. Pretreatment of the strips with the catechol O-methyltransferase (COMT) inhibitors tropolone or pyrogallol or the inhibitor of extraneuronal uptake 17β-estradiol blocked the potentiation by ketamine; in addition, potentiation by the COMT and extraneuronal uptake inhibitors was abolished or greatly reduced by ketamine. In rabbit aorta, ketamine potentiated responses to the catecholamines (adrenaline > nordefrine > noradrenaline) but not to the noneatecholamines phenylephrine, methoxamine, and synephrine; instead a slight relaxant effect was observed. Ketamine potentiated, whereas cocaine inhibited, responses to tyramine. Experiments using the technique of oil immersion demonstrated that ketamine reduced the rate at which aortic strips inactivate adrenaline even when monoamine oxidase (MAO) and neuronal uptake processes were fully inhibited. Uptake studies showed that ketamine and 17β-estradiol reduced extraneuronal accumulation of [3H]adrenaline in aortic strips. We conclude that ketamine is an inhibitor of extraneuronal uptake in the vascular smooth muscles studied and the importance of this mechanism in producing its known cardiovascular effect is discussed.

Abstract 73: Nanoformulated Copper/Zinc Superoxide Dismutase: Alternative Therapeutic Strategy for Angiotensin II-dependent Neurogenic Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Krupa K Savalia ◽  
Devika S Manickam ◽  
Erin G Rosenbaugh ◽  
Jun Tian ◽  
Iman Ahmad ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Angiotensin Ii ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
In Vivo Studies ◽  
Neuronal Uptake ◽  
Neurogenic Hypertension ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Copper Zinc

Excessive production of superoxide (O2•-) in the central nervous system has been widely implicated in the pathogenesis of angiotensin II (AngII)-dependent neurogenic hypertension (HTN). Our group has tried to overcome the failed therapeutic potential of currently available antioxidants by utilizing nanoformulated copper/zinc superoxide dismutase (SOD1), so-called SOD1 nanozymes, that specifically scavenges intracellular O2•-. These nanozymes consist of SOD1 protein wrapped with cationic block copolymers followed by covalent cross-linking of the polycation template (cl-nano). We hypothesize that cl-nano delivers active SOD1 protein to neurons and can effectively decrease blood pressure in a mouse model of AngII-dependent neurogenic HTN. As determined by electron paramagnetic resonance (EPR) spectroscopy, cl-nano retains SOD1 activity and scavenges O2•- to levels comparable with native SOD1 protein in a cell-free environment (EPR arbitrary units: vehicle 1.12e6 ± 1.79e5; native SOD1 protein 4.45e4 ± 3.00e3; cl-nano 6.78e4 ± 1.74e3, p<0.05 vs. vehicle). Experiments to examine neuronal uptake of cl-nano, analyzed by western blot and SOD1 activity assays, reveal that cl-nano delivers active SOD1 to central neurons in culture (CATH.a neurons) more efficiently than native SOD1 protein following 1 hour treatment (SOD1 activity in units/mg protein: vehicle 336; native SOD1 protein 313; cl-nano 718). Furthermore, in vivo studies demonstrate that HTN established by chronic subcutaneous infusion of AngII (400 ng/kg/min) is significantly attenuated following a single intracerebroventricular (ICV) injection of cl-nano for up to 7 days (mean arterial pressure (MAP) in mmHg: pre-AngII 87 ± 3; 9 days post-AngII 138 ± 6; 7 days post-ICV injection of cl-nano 112 ± 4, p<0.05 vs. pre-ICV injection). These data provide evidence for the efficacy of nanoformulated SOD1 in counteracting excessive O2•- and decreasing MAP in AngII-dependent hypertensive mice when injected directly into the brain. Although further experiments must be performed with more clinically relevant routes of cl-nano administration, such as intravenous injection, this study supports the further development of cl-nano with SOD1 as an alternative therapeutic option for HTN.

Effects of corticoadrenal extract on the neuronal and extraneuronal uptake of noradrenaline in the isolated rabbit heart

1985 ◽  
Vol 72 (2) ◽  
pp. 94-95
Author(s):  
Pham Huu Chanh ◽  
R. Kaiser ◽  
R. Chahine ◽  
K. Abou Khalil ◽  
M. Abou-Assaly ◽  
...  
Keyword(s):  
Rabbit Heart ◽  
Extraneuronal Uptake ◽  
Isolated Rabbit Heart ◽  
Uptake Of Noradrenaline

scholarly journals Identification of the angiotensin II receptor in rat mesenteric artery

1984 ◽  
Vol 223 (3) ◽  
pp. 659-671 ◽  
Author(s):  
J McQueen ◽  
G D Murray ◽  
P F Semple
Keyword(s):  
Angiotensin Ii ◽  
Binding Sites ◽  
Radioligand Binding ◽  
Specific Binding ◽  
Divalent Cations ◽  
Target Tissue ◽  
Angiotensin Ii Receptor ◽  
High Affinity ◽  
Rat Mesentery ◽  
Rat Mesenteric Artery

Specific binding sites of high affinity and low capacity for 125I-angiotensin II have been identified in a membrane fraction derived from arterial arcades of the rat mesentery. Heterogeneity of binding sites and extensive tracer degradation necessitated the use of nonlinear regression methods for the analysis of radioligand binding data. Forward and reverse rate constants for the high affinity sites obtained by three experimental approaches were in good agreement and gave a dissociation equilibrium constant (Kd) of 19-74 pM (95% confidence interval). Affinities for a number of angiotensin-related peptides calculated from competitive binding curves were in the order 125I-angiotensin II = angiotensin II greater than angiotensin III greater than [Sar1,Ile8]angiotensin II greater than [Sar1,Gly8]angiotensin II. Angiotensin I and biochemically unrelated peptides had virtually no effect on binding of tracer angiotensin II. The divalent cations Mn2+, Mg2+ and Ca2+ stimulated 125I-angiotensin II binding at concentrations of 2-10 mM, as did Na+ at 50-100 mM. In the presence of Na+ or Li+, K+ had a biphasic effect. The chelating agents EDTA and EGTA were inhibitory, as were the thiol reagents dithiothreitol and cysteine. This study defined angiotensin II binding sites in a vascular target tissue of sufficiently high affinity to interact rapidly with plasma angiotensin II at physiological concentrations.

scholarly journals Diastolic wall stress and ANG II in cardiac hypertrophy and gene expression induced by volume overload

2000 ◽  
Vol 279 (6) ◽  
pp. H2939-H2946 ◽  
Author(s):  
Hiroshi Yamakawa ◽  
Takuroh Imamura ◽  
Takeshi Matsuo ◽  
Hisamitsu Onitsuka ◽  
Yoko Tsumori ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Channel Blocker ◽  
Volume Overload ◽  
Wall Stress ◽  
Left Ventricular ◽  
Expression Level ◽  
Ang Ii ◽  
Similar Extent

We investigated the effects of diastolic wall stress (WS) and angiotensin II (ANG II) on the left ventricular (LV) hypertrophy (LVH) induced by volume overload and on the gene expression of LV adrenomedullin (AM) and atrial natriuretic peptide (ANP) in volume overload. Diastolic WS was pharmacologically manipulated with (candesartan) or without (calcium channel blocker manidipine) inhibition of ANG II type 1 receptors in aortocaval-shunted rats over 6 wk. Diastolic WS reached a plateau at 2 wk and subsequently declined regardless of further LVH. Although diastolic WS was decreased to a similar extent by both compounds, candesartan blunted LVH over 6 wk, whereas manidipine blunted LVH at 2 wk but not after 4 wk. Levels of AM and ANP gene expression increased as LVH developed but were completely suppressed by candesartan over 6 wk. ANP expression level was also attenuated by manidipine over 6 wk, whereas AM expression level was suppressed at 2 wk but not after 4 wk by manidipine. We concluded that diastolic WS and ANG II might be potent stimuli for the LVH and LV AM and ANP gene expression in volume overload and that diastolic WS could be relatively involved in the early LVH and in the gene expression of ANP rather than of AM.

Effects of angiotensin II on regional afferent and efferent arteriole dimensions and the glomerular pole

2000 ◽  
Vol 279 (2) ◽  
pp. R629-R638 ◽  
Author(s):  
Kate M. Denton ◽  
Warwick P. Anderson ◽  
Raja Sinniah
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Capillary Pressure ◽  
Ang Ii ◽  
Similar Extent ◽  
Outer Cortex ◽  
Efferent Arteriole ◽  
Vascular Casting ◽  
Cortical Regions ◽  
Inner Cortex

The diversity of renal arteriole diameters in different cortical regions has important consequences for control of glomerular capillary pressure. We examined whether intrarenal angiotensin II (ANG II; 0.1, 1, or 5 ng · kg−1 · min−1) in anesthetized rabbits acts preferentially on pre- or postglomerular vessels using vascular casting. ANG II produced dose-related reductions in afferent and efferent diameters in the outer, mid, and inner cortex, without effecting arterial pressure. Afferent diameter decreased more than efferent in the outer and mid cortex ( P < 0.05) but by a similar extent in juxtamedullary nephrons ( P = 0.58). Calculated efferent resistance increased more than afferent, especially in the outer cortex (127 vs. 24 units; 5 ng · kg−1 · min−1 ANG II). ANG II produced significant dose-related increases in the distance between the arterioles at the entrance to the glomerular pole in all regions. Thus afferent diameter decreased more in response to ANG II, but efferent resistance rose more due to smaller resting luminal dimensions. The results also indicate that glomerular pole dimensions change in response to ANG II.

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