Dependence of Deoxycorticosterone/Salt Hypertension in the Rat on the Activity of Adrenergic Cardiac Nerves

Bell, Christopher; McLachlan, Elspeth M.

doi:10.1042/cs0570203

Cited by 24 publications

(14 citation statements)

References 31 publications

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“…This is consistent with previous studies, which demonstrated that these two mineralocorticoids could inhibit the clearance of epinephrine and norepinephrine, and potentiate their actions in vascular or cardiac tissue [11,12,50,51]. This is the first study demonstrating mineralocorticoid-sensitive transport in CNS cells, and suggests that mineralocorticoids also exert actions in the CNS by inhibiting uptake2-mediated monoamine clearance.…”

supporting

confidence: 80%

Natural and synthetic corticosteroids inhibit uptake2-mediated transport in CNS neurons

Hill

Makky

Shrestha

et al. 2011

Physiology & Behavior

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In addition to exerting actions via mineralocorticoid and glucocorticoid receptors, corticosteroids also act by inhibiting uptake2, a highcapacity monoamine transport system originally described in peripheral tissues. Recent studies have demonstrated that uptake2 transporters are expressed in the brain and play roles in monoamine clearance, suggesting that they mediate some corticosteroid effects on physiological and behavioral processes. However, the sensitivity of brain uptake2 to many natural and synthetic corticosteroids has not been characterized. Cultured rat cerebellar granule neurons (CGNs) were previously shown to exhibit corticosteronesensitive accumulation of the uptake2 substrate1-methyl-4-phenylpyridinium (MPP + ). We examined the expression of uptake1 and uptake2 transporters in CGNs, and tested the effects of a variety of natural and synthetic corticosteroids on accumulation of [ 3 H]-MPP + by these cells. Cultured rat CGNs expressed mRNA for three uptake2-like transporters: organic cation transporters 1 and 3, and the plasma membrane monoamine transporter. They did not express mRNA for the dopamine or norepinephrine transporters, and expressed very little mRNA for the serotonin reuptake transporter. Accumulation of [3 H]-MPP + by CGNs was dose-dependently inhibited by corticosterone and decynium-22, known inhibitors of uptake2. Accumulation of MPP + was also dose-dependently inhibited, with varying efficacies, by aldosterone, 11-deoxycorticosterone, cortisol, and cortisone, and by the synthetic glucocorticoids betamethasone, dexamethasone and prednisolone, and the glucocorticoid receptor antagonist RU38486. These studies demonstrate that uptake2 in the CNS is inhibited by a variety of natural and synthetic corticosteroids, and suggest that inhibition of uptake2-mediated monoamine clearance may underlie some behavioral and physiological effects of these hormones.

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supporting

confidence: 80%

Natural and synthetic corticosteroids inhibit uptake2-mediated transport in CNS neurons

Hill

Makky

Shrestha

et al. 2011

Physiology & Behavior

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“…The sympathetic nervous system may be important in the pathogenesis of deoxycorticosterone salt hypertension in rats4, 5 and pigs6 but not in dogs7 or baboons. * In humans, studies using a variety of methods showed that sympathetic activity was depressed9,10 or unchanged.Il2 12 in man to test the hypothesis that the ANS contributes to the hypertensive effect of cortisol and that autonomic blockade will reverse cortisol induced hypertension.…”

Section: Introductionmentioning

confidence: 99%

Autonomic Blockade Amplifies Cortisol‐induced Hypertension in Man

Tam

Williamson

Kelly

et al. 1997

Clin Exp Pharma Physio

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1. We investigated the role of the autonomic nervous system (ANS) in cortisol induced hypertension using the technique of total autonomic blockade (AB). 2. Four healthy young males were given 50 mg cortisol 6 hourly for 6 days. On the day prior to, and the last day of, cortisol treatment, AB was produced using oral prazosin 1 mg, intravenous clonidine 300 micrograms, propranolol 0.2 mg/kg and atropine 2 mg. The adequacy of blockade was assessed using the haemodynamic response to Valsalva manoeuvre. 3. Cortisol produced a significant rise in systolic blood pressure (130 +/- 2 vs 110 +/- 1 mmHg, pre vs post cortisol; P < 0.01). On the final treatment day, AB augmented the increase in diastolic blood pressure (delta DBP), mean arterial pressure (delta MAP) and heart rate (delta HR) compared to the pretreatment day, delta DBP: 43 +/- 6 vs 17 +/- 4 mmHg, post vs pre cortisol, P < 0.005, delta MAP: 39 +/- 4 vs 14 +/- 4 mmHg, P < 0.001, delta HR: 45 +/- 5 vs 26 +/- 4 b.p.m., P < 0.05. The change in systolic blood pressure (delta SBP) was not statistically significant (32 +/- 4 vs 7 +/- 3 mmHg, P = 0.065). 4. These results suggest that the ANS exerts a modulating influence on the hypertensive effect of cortisol.

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“…Neonatal rats postnatally received capsaicin 50 mg/kg SC per day for 2 days and/or guanethidine 80 mg/kg SC per day for 2 weeks. 18,19 Capsaicin is a selective toxin of sensory neurons, and guanethidine causes sympathectomy. Control rats were treated with equal volumes of vehicle solution (5% ethanol, 5% Tween 80 in saline).…”

Section: Animalsmentioning

confidence: 99%

Degeneration of Capsaicin-Sensitive Sensory Nerves Leads to Increased Salt Sensitivity Through Enhancement of Sympathoexcitatory Response

Wang

Lookingland

2001

Hypertension

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Abstract-We have previously shown that neonatal degeneration of capsaicin-sensitive sensory nerves renders a rat responsive to a salt load with an increase in blood pressure and a decrease in natriuretic response. To test the hypothesis that the enhanced sympathoexcitatory response to a high salt intake contributes to the development of hypertension in this model, newborn Wistar rats were given 50 mg/kg capsaicin and/or 80 mg/kg guanethidine subcutaneously. Control rats were treated with vehicle. After the weaning period, male rats were grouped as the following and given a high sodium diet (4%) for 2 weeks: capsaicin and guanethidine coadministration (CAP-GUA), capsaicin only (CAP), guanethidine only (GUA), and vehicle control (CON). Norepinephrine concentrations in the atrium were significantly lower in CAP-GUA and GUA than in CON rats (PϽ0.05). Twenty-four-hour urine and sodium excretions were significantly lower in CAP than in CAP-GUA, GUA, and CON rats (PϽ0.05). Mean arterial pressure (mm Hg) was significantly higher in CAP (180Ϯ10) than in CAP-GUA (106Ϯ1), GUA (133Ϯ5), and CON (122Ϯ3) rats (PϽ0.05). Thus, sympathectomy restores the natriuretic response to a high salt intake and prevents the development of salt-sensitive hypertension induced by sensory denervation. These data indicate that sensory nerves counterbalance the prohypertensive effect of the sympathetic nerves to maintain blood pressure within normal range during salt loading. Key Words: denervation Ⅲ sympathectomy Ⅲ hypertension, sodium-dependent Ⅲ sodium, dietary S omatosensory input normally inhibits sympathetic nerve activity through the nucleus of the solitary tract pathway. 1,2 Attenuation of this inhibition may lead to increased sympathetic nerve activity. [3][4][5] Previous studies show that decreased responsiveness of sensory neurons contributes to increased renal sympathetic nerve activity and sodium retention in spontaneously hypertensive rats. 6,7 Conversely, longterm ablation of sympathetic neurons is followed by an increase in the afferent innervation. 8 -10 These studies support the concept that an alteration of the normal balance between sensory and sympathetic nerves by eliminating either of these nerve populations will lead to hyperresponsiveness or hyperinnervation of the remaining nerve population.In addition to the function traditionally known as "sensing" changes in the environment and transmitting the information to the central nervous system, sensory fibers have local effector function through releasing a variety of vasodilator neuropeptides, for example, calcitonin gene-related peptide (CGRP) and substance P, peripherally in response to local stimuli. 10 The cell bodies of these afferent fibers are located in the dorsal root ganglia (DRG), in which sensory neurotransmitters are synthesized and stored. These sensory neurotransmitters may directly affect blood pressure by modulation of cardiovascular and renal function. 10,11 For example, it has been shown that CGRP and substance P are not only potent vasodilators but also ...

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Dependence of Deoxycorticosterone/Salt Hypertension in the Rat on the Activity of Adrenergic Cardiac Nerves

Cited by 24 publications

References 31 publications

Natural and synthetic corticosteroids inhibit uptake2-mediated transport in CNS neurons

Natural and synthetic corticosteroids inhibit uptake2-mediated transport in CNS neurons

Autonomic Blockade Amplifies Cortisol‐induced Hypertension in Man

Degeneration of Capsaicin-Sensitive Sensory Nerves Leads to Increased Salt Sensitivity Through Enhancement of Sympathoexcitatory Response

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