ATP and norepinephrine contributions to sympathetic vasoconstriction of tail artery are altered in streptozotocin-diabetic rats.
Sympathetic vasoconstriction is susceptible to diabetes, but contributions made by purinergic neurotransmission in this state have not been investigated. We aimed to evaluate sympathetic vasoconstriction contributions by ATP and norepinephrine in the tail artery from streptozotocin-diabetic rats by using isometric vascular rings. Tail arteries were isolated from rats made diabetic 3 mo earlier with streptozotocin (diabetic group), age-matched nondiabetic rats (nondiabetic injected), age-matched untreated animals (noninjected normal), and age-matched untreated animals in high glucose control Krebs solution (high glucose control). Responses to KCl (60 mM) or nerve stimulus trains of 1-100 impulses were identical in all groups. Electrical stimulation produced progressively greater contractions with increasing impulse numbers. These were partially reduced by suramin (100 microM, P2 antagonist), NF-279 (1 microM, P2X blocker), and phentolamine (2 microM, alpha-blocker). For purinergic antagonists, blockade was greater in diabetic vessels compared with that in others. No differential effect could be detected for phentolamine between groups. Bath-applied ATP (1 nM-1 mM) and norepinephrine (0.1 nM-100 microM) showed increased potency with diabetic group vessels. Desipramine (1 microM, norepinephrine reuptake inhibitor) potentiated neurally evoked responses in all groups equally and increased sensitivity to exogenous norepinephrine in a similar fashion. Histochemical labeling of sympathetic nerves with neuronal marker protein PGP-9.5 and a sympathetic nerve-specific antibody for tyrosine hydroxylase showed no reduction in diabetic innervation density. We demonstrate, for the first time, changes in contributions of ATP and norepinephrine in sympathetic responses of rat tail artery in diabetes, which cannot be accounted for by axonal degeneration or by changes in norepinephrine reuptake.
Speirs
Lynne
L
Dept. of Physiology, Medical Biology Centre, Queen's Univ. of Belfast, 97 Lisburn Rd., Belfast, UK.
Donnelly
Aisling
A
Lynch
Joanne
J
Scholfield
C Norman
CN
Johnson
Christopher
C
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013623:Tail / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D058919:Purinergic P2 Receptor Antagonists; D014662:Vasoconstrictor Agents; D000255:Adenosine Triphosphate; D009638:Norepinephrine