Altered cotransmitter contributions to sympathetic vasoconstriction in tail artery of streptozotocin diabetic rats. (J. Physiol. 539P, ) (Oral presentation): Proceedings of the Physiological Society

A. Donnelly, Sean Roe, Christopher Johnson, C Scholfield

Research output: Contribution to conferenceAbstract

Abstract

Diabetes mellitus is associated with numerous cardiovascular complications including autonomic neuropathy, leading to orthostatic hypotension. Changes taking place in sensitivity to exogenous noradrenaline are well documented (Weber et al. 1996) but contributions of other sympathetically released cotransmitters are unclear. In this study we show that vascular responses mediated by ATP in the rat tail artery show distinct changes in the diabetic state. Sprague-Dawley rats (8 week old, male) were made diabetic by intraperitoneal injection (60 mg kg-1) of streptozotocin and maintained for a further 12 weeks in accordance with UK legislation. Animals were killed by cervical dislocation. Injected animals having a blood glucose of less than 10 mM/l were used a controls (n = 9, 492 ± 26 g, mean ± S.E.M.; blood glucose 7 ± 1 mM) while those with higher values were deemed to be diabetic (n = 12, 275 ± 12 g, blood glucose 39 ± 2 mM). Tail arteries were excised, endothelium removed and rings cut into 3-5 mm lengths. Isometric contractions were measured. Noradrenaline (0.1 nM-100 µM) and ATP (1 nM-10 µM) were bath applied and dose-response curves constructed and responses examined to either 60 mM KCl or electrical field stimulation by trains of 1-100 impulses (at 20 Hz, 1 ms pulses, supra-maximal voltage). Electrically-evoked responses were examined in the absence or presence of non-specific α-adrenoceptor antagonist, phentolamine (1 µM), or P2 purinoceptor antagonist, suramin (100 µM). Electrically-evoked responses were abolished in the presence of tetrodotoxin (1 µM) or guanethidine (10 µM), indicating their sympathetic origin. Bath applied noradrenaline and ATP were both more potent in diabetic than non-diabetic arteries (diabetic vs. non-diabetic, ED50 for noradrenaline: 0.28 ± 0.07 vs. 2.93 ± 1.0 µM: P < 0.005, unpaired t test). In contrast, there were no differences in KCl constrictions between diabetic and non-diabetic rats (0.94 ± 0.2 g and 0.85 ± 0.07 g respectively; unpaired t test) suggesting the enhanced vasoconstrictor responses were not due to changes in smooth muscle contractility. Nerve stimulation produced contractions which were similar in both diabetic and non-diabetic arteries. In non-diabetic arteries, these were reduced by suramin which was dependent on train impulse number, ie, 58 ± 12 % depression with 2 pulses and 27 ± 13 % 100 impulses). However, in diabetic arteries, depression with suramin was greater for longer pulse trains (depressions of 54 ± 12 % and 68 ± 10 % for 2 and 100 pulse trains; one way ANOVA and SNK, diabetic vs. non-diabetic). There were also depressions with phentolamine which was similar for both groups for impulse trains >4 (one way ANOVA). Thus, we have shown that in diabetic rats, responses to sympathetic activation are preserved but there is a shift towards a greater contribution made by ATP which is dependent on pulse train parameters.
Original languageEnglish
Pages104P
Number of pages1
Publication statusPublished - 2004
EventPhysiological Society Meeting Cambridge - Cambridge, Cambridge, United Kingdom
Duration: 01 Dec 200424 Jan 2019

Conference

ConferencePhysiological Society Meeting Cambridge
CountryUnited Kingdom
CityCambridge
Period01/12/200424/01/2019

Fingerprint

Streptozocin
Vasoconstriction
Tail
Norepinephrine
Arteries
Adenosine Triphosphate
Blood Glucose
Baths
Purinergic P2 Receptor Antagonists
Guanethidine
Suramin
Orthostatic Hypotension
Isometric Contraction
Phentolamine
Tetrodotoxin
Intraperitoneal Injections
Legislation
Adrenergic Receptors
Electric Stimulation
Endothelium

Keywords

  • Physiology
  • Pharmacology

Cite this

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title = "Altered cotransmitter contributions to sympathetic vasoconstriction in tail artery of streptozotocin diabetic rats. (J. Physiol. 539P, ) (Oral presentation): Proceedings of the Physiological Society",
abstract = "Diabetes mellitus is associated with numerous cardiovascular complications including autonomic neuropathy, leading to orthostatic hypotension. Changes taking place in sensitivity to exogenous noradrenaline are well documented (Weber et al. 1996) but contributions of other sympathetically released cotransmitters are unclear. In this study we show that vascular responses mediated by ATP in the rat tail artery show distinct changes in the diabetic state. Sprague-Dawley rats (8 week old, male) were made diabetic by intraperitoneal injection (60 mg kg-1) of streptozotocin and maintained for a further 12 weeks in accordance with UK legislation. Animals were killed by cervical dislocation. Injected animals having a blood glucose of less than 10 mM/l were used a controls (n = 9, 492 ± 26 g, mean ± S.E.M.; blood glucose 7 ± 1 mM) while those with higher values were deemed to be diabetic (n = 12, 275 ± 12 g, blood glucose 39 ± 2 mM). Tail arteries were excised, endothelium removed and rings cut into 3-5 mm lengths. Isometric contractions were measured. Noradrenaline (0.1 nM-100 µM) and ATP (1 nM-10 µM) were bath applied and dose-response curves constructed and responses examined to either 60 mM KCl or electrical field stimulation by trains of 1-100 impulses (at 20 Hz, 1 ms pulses, supra-maximal voltage). Electrically-evoked responses were examined in the absence or presence of non-specific α-adrenoceptor antagonist, phentolamine (1 µM), or P2 purinoceptor antagonist, suramin (100 µM). Electrically-evoked responses were abolished in the presence of tetrodotoxin (1 µM) or guanethidine (10 µM), indicating their sympathetic origin. Bath applied noradrenaline and ATP were both more potent in diabetic than non-diabetic arteries (diabetic vs. non-diabetic, ED50 for noradrenaline: 0.28 ± 0.07 vs. 2.93 ± 1.0 µM: P < 0.005, unpaired t test). In contrast, there were no differences in KCl constrictions between diabetic and non-diabetic rats (0.94 ± 0.2 g and 0.85 ± 0.07 g respectively; unpaired t test) suggesting the enhanced vasoconstrictor responses were not due to changes in smooth muscle contractility. Nerve stimulation produced contractions which were similar in both diabetic and non-diabetic arteries. In non-diabetic arteries, these were reduced by suramin which was dependent on train impulse number, ie, 58 ± 12 {\%} depression with 2 pulses and 27 ± 13 {\%} 100 impulses). However, in diabetic arteries, depression with suramin was greater for longer pulse trains (depressions of 54 ± 12 {\%} and 68 ± 10 {\%} for 2 and 100 pulse trains; one way ANOVA and SNK, diabetic vs. non-diabetic). There were also depressions with phentolamine which was similar for both groups for impulse trains >4 (one way ANOVA). Thus, we have shown that in diabetic rats, responses to sympathetic activation are preserved but there is a shift towards a greater contribution made by ATP which is dependent on pulse train parameters.",
keywords = "Physiology, Pharmacology",
author = "A. Donnelly and Sean Roe and Christopher Johnson and C Scholfield",
year = "2004",
language = "English",
pages = "104P",
note = "Physiological Society Meeting Cambridge ; Conference date: 01-12-2004 Through 24-01-2019",

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Altered cotransmitter contributions to sympathetic vasoconstriction in tail artery of streptozotocin diabetic rats. (J. Physiol. 539P, ) (Oral presentation) : Proceedings of the Physiological Society. / Donnelly, A.; Roe, Sean; Johnson, Christopher; Scholfield, C.

2004. 104P Abstract from Physiological Society Meeting Cambridge , Cambridge, United Kingdom.

Research output: Contribution to conferenceAbstract

TY - CONF

T1 - Altered cotransmitter contributions to sympathetic vasoconstriction in tail artery of streptozotocin diabetic rats. (J. Physiol. 539P, ) (Oral presentation)

T2 - Proceedings of the Physiological Society

AU - Donnelly, A.

AU - Roe, Sean

AU - Johnson, Christopher

AU - Scholfield, C

PY - 2004

Y1 - 2004

N2 - Diabetes mellitus is associated with numerous cardiovascular complications including autonomic neuropathy, leading to orthostatic hypotension. Changes taking place in sensitivity to exogenous noradrenaline are well documented (Weber et al. 1996) but contributions of other sympathetically released cotransmitters are unclear. In this study we show that vascular responses mediated by ATP in the rat tail artery show distinct changes in the diabetic state. Sprague-Dawley rats (8 week old, male) were made diabetic by intraperitoneal injection (60 mg kg-1) of streptozotocin and maintained for a further 12 weeks in accordance with UK legislation. Animals were killed by cervical dislocation. Injected animals having a blood glucose of less than 10 mM/l were used a controls (n = 9, 492 ± 26 g, mean ± S.E.M.; blood glucose 7 ± 1 mM) while those with higher values were deemed to be diabetic (n = 12, 275 ± 12 g, blood glucose 39 ± 2 mM). Tail arteries were excised, endothelium removed and rings cut into 3-5 mm lengths. Isometric contractions were measured. Noradrenaline (0.1 nM-100 µM) and ATP (1 nM-10 µM) were bath applied and dose-response curves constructed and responses examined to either 60 mM KCl or electrical field stimulation by trains of 1-100 impulses (at 20 Hz, 1 ms pulses, supra-maximal voltage). Electrically-evoked responses were examined in the absence or presence of non-specific α-adrenoceptor antagonist, phentolamine (1 µM), or P2 purinoceptor antagonist, suramin (100 µM). Electrically-evoked responses were abolished in the presence of tetrodotoxin (1 µM) or guanethidine (10 µM), indicating their sympathetic origin. Bath applied noradrenaline and ATP were both more potent in diabetic than non-diabetic arteries (diabetic vs. non-diabetic, ED50 for noradrenaline: 0.28 ± 0.07 vs. 2.93 ± 1.0 µM: P < 0.005, unpaired t test). In contrast, there were no differences in KCl constrictions between diabetic and non-diabetic rats (0.94 ± 0.2 g and 0.85 ± 0.07 g respectively; unpaired t test) suggesting the enhanced vasoconstrictor responses were not due to changes in smooth muscle contractility. Nerve stimulation produced contractions which were similar in both diabetic and non-diabetic arteries. In non-diabetic arteries, these were reduced by suramin which was dependent on train impulse number, ie, 58 ± 12 % depression with 2 pulses and 27 ± 13 % 100 impulses). However, in diabetic arteries, depression with suramin was greater for longer pulse trains (depressions of 54 ± 12 % and 68 ± 10 % for 2 and 100 pulse trains; one way ANOVA and SNK, diabetic vs. non-diabetic). There were also depressions with phentolamine which was similar for both groups for impulse trains >4 (one way ANOVA). Thus, we have shown that in diabetic rats, responses to sympathetic activation are preserved but there is a shift towards a greater contribution made by ATP which is dependent on pulse train parameters.

AB - Diabetes mellitus is associated with numerous cardiovascular complications including autonomic neuropathy, leading to orthostatic hypotension. Changes taking place in sensitivity to exogenous noradrenaline are well documented (Weber et al. 1996) but contributions of other sympathetically released cotransmitters are unclear. In this study we show that vascular responses mediated by ATP in the rat tail artery show distinct changes in the diabetic state. Sprague-Dawley rats (8 week old, male) were made diabetic by intraperitoneal injection (60 mg kg-1) of streptozotocin and maintained for a further 12 weeks in accordance with UK legislation. Animals were killed by cervical dislocation. Injected animals having a blood glucose of less than 10 mM/l were used a controls (n = 9, 492 ± 26 g, mean ± S.E.M.; blood glucose 7 ± 1 mM) while those with higher values were deemed to be diabetic (n = 12, 275 ± 12 g, blood glucose 39 ± 2 mM). Tail arteries were excised, endothelium removed and rings cut into 3-5 mm lengths. Isometric contractions were measured. Noradrenaline (0.1 nM-100 µM) and ATP (1 nM-10 µM) were bath applied and dose-response curves constructed and responses examined to either 60 mM KCl or electrical field stimulation by trains of 1-100 impulses (at 20 Hz, 1 ms pulses, supra-maximal voltage). Electrically-evoked responses were examined in the absence or presence of non-specific α-adrenoceptor antagonist, phentolamine (1 µM), or P2 purinoceptor antagonist, suramin (100 µM). Electrically-evoked responses were abolished in the presence of tetrodotoxin (1 µM) or guanethidine (10 µM), indicating their sympathetic origin. Bath applied noradrenaline and ATP were both more potent in diabetic than non-diabetic arteries (diabetic vs. non-diabetic, ED50 for noradrenaline: 0.28 ± 0.07 vs. 2.93 ± 1.0 µM: P < 0.005, unpaired t test). In contrast, there were no differences in KCl constrictions between diabetic and non-diabetic rats (0.94 ± 0.2 g and 0.85 ± 0.07 g respectively; unpaired t test) suggesting the enhanced vasoconstrictor responses were not due to changes in smooth muscle contractility. Nerve stimulation produced contractions which were similar in both diabetic and non-diabetic arteries. In non-diabetic arteries, these were reduced by suramin which was dependent on train impulse number, ie, 58 ± 12 % depression with 2 pulses and 27 ± 13 % 100 impulses). However, in diabetic arteries, depression with suramin was greater for longer pulse trains (depressions of 54 ± 12 % and 68 ± 10 % for 2 and 100 pulse trains; one way ANOVA and SNK, diabetic vs. non-diabetic). There were also depressions with phentolamine which was similar for both groups for impulse trains >4 (one way ANOVA). Thus, we have shown that in diabetic rats, responses to sympathetic activation are preserved but there is a shift towards a greater contribution made by ATP which is dependent on pulse train parameters.

KW - Physiology

KW - Pharmacology

UR - http://www.physoc.org/proceedings/abstract/J%20Physiol%20555PC36

M3 - Abstract

SP - 104P

ER -