Effects on renal sympathetic axons in dog of acute 6-hydroxydopamine treatment in combination with selective neuronal uptake inhibitors

Peripheral- and central nervous system (CNS)-mediated effects of desipramine (Des) on sympathetic nerves and the contribution of alpha 2-adrenoceptors to these effects were studied in conscious rabbits. Blood pressure, renal sympathetic nerve activity (SNA), and norepinephrine (NE) reuptake and spillover into plasma were measured before and after intracisternal (ic) or intravenous (i.v.) administration of Des. In other animals, NE spillover responses to i.v. Des were examined before and after alpha 2-adrenoceptor blockade with i.v. idazoxan. Treatment with i.v. Des blocked neuronal reuptake and decreased renal SNA but did not alter blood pressure or NE spillover. Decreased NE release by sympathetic nerves after i.v. Des was reflected by a decrease in the combined rate of NE reuptake and spillover. Treatment with ic Des (at 1.7% of the i.v. dose) decreased blood pressure and renal SNA and produced equivalent falls in NE reuptake and spillover, indicating little peripheral effect of centrally administered Des on the efficiency of neuronal reuptake. Thus Des had two distinct actions: the drug blocked neuronal reuptake by direct actions on nerve endings and reduced SNA by actions within the CNS. After ic Des, decreased SNA produced parallel falls in NE reuptake, spillover, and blood pressure. After i.v. Des, blockade of neurotransmitter reuptake increased NE concentrations at sympathoeffector junctions offsetting the fall in SNA, so that there was little change in NE spillover or blood pressure. However, after alpha 2-adrenoceptor blockade with i.v. idazoxan, NE spillover increased in response to i.v. Des. Thus the Des-induced decrease in NE release was partly mediated by an action of raised intrasynaptic NE concentrations on inhibitory alpha 2-adrenoceptors.

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Splanchnic nerve response to A5 area stimulation in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.263.2.r437 ◽

1992 ◽

Vol 263 (2) ◽

pp. R437-R446 ◽

Cited By ~ 6

Author(s):

D. Huangfu ◽

L. J. Hwang ◽

T. A. Riley ◽

P. G. Guyenet

Keyword(s):

Receptor Antagonist ◽

Excitatory Amino Acid ◽

Splanchnic Nerve ◽

Nerve Response ◽

A5 Area ◽

6 Hydroxydopamine ◽

Renal Sympathetic ◽

Made In ◽

Stimulation Of ◽

Intraspinal Injection

Microinjection of the excitatory amino acid N-methyl-D-aspartate (NMDA, 0.5 nmol) into ventrolateral pons (the A5 area) of halothane-anesthetized, paralyzed rats increased splanchnic (sSND) and renal sympathetic nerve discharges (approximately 45%) and usually decreased lumbar SND. These effects were accompanied by 1) regionally specific changes in vascular resistances, 2) an increase in the gain of the sympathetic baroreflex, and 3) modest reductions in blood pressure and heart rate. sSND activation was greatest when NMDA injections were made in the vicinity of A5 noradrenergic (NE) cells. Injection of 6-hydroxydopamine (6-OH-DA) into A5 area (after 15 days) destroyed 83% of NE neurons and reduced NMDA activation of sSND by 76%. Stimulation of sSND by NMDA in A5 area was reduced 1) 1-2 h after bilateral intraspinal injection of 6-OHDA, but not vehicle or 5,7-dihydroxytryptamine, and 2) by administration of prazosin [alpha 1-NE receptor antagonist, 1 mg/kg iv or 10-20 micrograms intrathecal (it)], but not by idazoxan (alpha 2-NE receptor antagonist, 10-20 micrograms it) or propranolol (0.2 mg/kg iv). We conclude that A5 NE cells have a visceral vasomotor sympathoexcitatory function mediated in large part by their spinal projection.

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Mechanism of action of vasoconstrictor responses to atriopeptin II in conscious SHR

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1985.249.6.r781 ◽

1985 ◽

Vol 249 (6) ◽

pp. R781-R786 ◽

Cited By ~ 1

Author(s):

R. W. Lappe ◽

J. A. Todt ◽

R. L. Wendt

Keyword(s):

Blood Flow ◽

Arterial Pressure ◽

Vascular Resistance ◽

Regional Blood Flow ◽

Sympathetic Nerves ◽

Spontaneously Hypertensive ◽

Regional Vascular Resistance ◽

6 Hydroxydopamine ◽

Renal Vascular ◽

Renal Sympathetic

Previous studies have demonstrated that infusion of synthetic atriopeptin II (AP II) lowered arterial pressure, reduced regional blood flow, and increased total peripheral and regional vascular resistances in conscious spontaneously hypertensive rats (SHR). This study was designed to examine the mechanism(s) involved in regional vasoconstrictor responses to AP II. In these experiments, hemodynamic actions of AP II were examined in control, 6-hydroxydopamine-treated (chemically sympathectomized), and renal-denervated groups of instrumented conscious SHR. Infusion of AP II (1 microgram X kg-1 X min-1) caused similar reductions in mean arterial pressure in control (-22 +/- 2 mmHg), chemically sympathectomized (-23 +/- 2 mmHg), and renal-denervated (-23 +/- 3 mmHg) SHR. In control SHR, AP II infusion reduced renal (-20 +/- 3%), mesenteric (-26 +/- 2%), and hindquarters (-18 +/- 10%) blood flow and increased regional vascular resistance in all three beds. Chemical sympathectomy prevented the fall in renal blood flow (RBF) and significantly abolished the regional vasoconstrictor responses to AP II infusion. In unilateral renal-denervated groups of SHR, AP II reduced renal vascular resistance (RVR) -11 +/- 3% but failed to alter RBF (-3 +/- 1%) in denervated kidneys. In contrast, RVR increased (20 +/- 7%) and RBF was significantly reduced (-29 +/- 3%) in contralateral-innervated kidneys. This study demonstrated that chemical or surgical destruction of renal sympathetic nerves abolished AP II-induced increases in RVR. These data further indicate that in conscious SHR the regional vasoconstrictor responses to AP II infusion appear to be mediated by increases in sympathetic tone rather than through direct vascular actions of AP II.

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

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y79-213 ◽

1979 ◽

Vol 57 (12) ◽

pp. 1443-1447 ◽

Cited By ~ 6

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.

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Neuronal and Vascular Reactivity in Isolated Perfused Kidneys during the Development of Spontaneous Hypertension

Clinical Science ◽

10.1042/cs055233s ◽

1978 ◽

Vol 55 (s4) ◽

pp. 233s-235s ◽

Cited By ~ 3

Author(s):

Michael G. Collis ◽

Paul M. Vanhoutte

Keyword(s):

Angiotensin Ii ◽

Nerve Stimulation ◽

Vascular Reactivity ◽

Barium Chloride ◽

Sympathetic Nerves ◽

Spontaneous Hypertension ◽

Neuronal Uptake ◽

Young Control ◽

Spontaneously Hypertensive ◽

Renal Sympathetic

1. Vascular reactivity was studied in Tyrode solution perfused kidneys from young (7 weeks) and mature (4–6 months) spontaneously hypertensive rats (SH rats). 2. The response to nerve stimulation was greater in the kidneys from young SH rats than in those from young control rats, both in control solution and after inhibition of the disposition of noradrenaline; both groups exhibited the same sensitivity to noradrenaline, angiotensin II and barium chloride. 3. The response to nerve stimulation was normal in kidneys from mature SH rats, but responses to noradrenaline, angiotensin II and barium chloride were greater than the control. 4. Cocaine potentiated the response to nerve stimulation more in the kidneys from mature SH rats than in those from the control rats. 5. The results suggest that renal sympathetic nerves release more noradrenaline than normal in the young SH rats, which could be an important factor in causing hypertension. 6. In the established phase of spontaneous hypertension the vascular reactivity to exogenous agonists is increased, probably as a consequence of high blood pressure; the more efficient neuronal uptake causes normalization of the response to sympathetic nerve stimulation.

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Effect of Neonatal Sympathectomy by 6-Hydroxydopamine on Volume and Resistance Regulation in Stroke-Prone Spontaneously Hypertensive Rats

Clinical Science ◽

10.1042/cs057201s ◽

1979 ◽

Vol 57 (s5) ◽

pp. 201s-204s ◽

Cited By ~ 4

Author(s):

A. Schömig ◽

R. Dietz ◽

W. Rascher ◽

H. Ebser ◽

U. Voss ◽

...

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Neuronal Uptake ◽

Compensatory Mechanism ◽

Hypertensive Rats ◽

Plasma Adrenaline ◽

Spontaneously Hypertensive ◽

Metabolism Of Noradrenaline ◽

6 Hydroxydopamine ◽

Neonatal Sympathectomy

1. Neonatal sympathectomy with 6 hydroxydopamine (6-OHDA) was used as a tool to assess the significance of an increased sympathetic vascular tone for the development of high blood pressure in stroke-prone spontaneously hypertensive rats. After administration of 6-OHDA the rise in blood pressure was blunted for the following 9 weeks until innervation was re-established. 6-OHDA-treated rats retained more sodium and had larger plasma and blood volumes than sham-treated rats. 2. Catecholamines in plasma were increased 2–10-fold immediately after sympathectomy, but their concentrations were subnormal on day 7. Eight weeks after sympathectomy plasma noradrenaline and dopamine were not elevated, but plasma adrenaline has increased twofold. 3. The reactivity of resistance vessels to noradrenaline was markedly enhanced and the neuronal uptake and metabolism of noradrenaline were still reduced 8 weeks after neonatal sympathectomy. 4. These results confirm the significance of an intact sympathetic nervous system for the development in these rats. Sodium retention and increased plasma and blood volume may be considered as a compensatory mechanism for the vasodilatation resulting from decreased vasomotor tone.

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Effect of Cocaine and Other Drugs on Sensitivity of the Estrogen-dominated Isthmus of Rabbit Oviduct to Noradrenaline

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y75-162 ◽

1975 ◽

Vol 53 (6) ◽

pp. 1172-1177 ◽

Cited By ~ 1

Author(s):

A. Johns ◽

D. M. Paton

Keyword(s):

Longitudinal Muscle ◽

Indirect Evidence ◽

Circular Muscle ◽

Muscle Layer ◽

Adrenergic Innervation ◽

Neuronal Uptake ◽

Isometric Contractions ◽

Histological Studies ◽

6 Hydroxydopamine ◽

Predominant Effect

The influence of the adrenergic innervation on the magnitude of responses of the isthmus of rabbit oviduct to (–)-noradrenaline was examined. Tissues were obtained from estrogen-dominated animals, and isometric contractions of longitudinal and circular muscle layers separately recorded. Longitudinal muscle was significantly more sensitive to (–)-noradrenaline. Cocaine potentiated responses of both circular and longitudinal muscle to (–)-noradrenaline, circular muscle being more potentiated. Similar results were obtained with desipramine. Tissues obtained from 6-hydroxydopamine pretreated animals did not respond to tyramine, and longitudinal and circular muscles were equisensitive to (–)-noradrenaline. Cocaine did not potentiate responses to (–)-noradrenaline in such tissues. Responses to (–)-noradrenaline were not altered by propranolol, hydrocortisone, or oxytetracycline. It was concluded that responses resulted from a predominant effect on α-receptors. The magnitude of responses to (–)-noradrenaline was mainly influenced by neuronal uptake of amine. Indirect evidence was obtained for a greater degree of adrenergic innervation to the circular muscle layer of the isthmus, in keeping with histological studies.

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