title: Prominent contribution of L-type Ca2+ channels to cutaneous neurovascular transmission that is revealed after spinal cord injury augments vasoconstriction.
abstract: In patients with spinal cord injury (SCI), somatosympathetic reflexes produce exaggerated decreases in skin blood flow below the lesion. This hypoperfusion appears to result from an increased responsiveness of cutaneous arterial vessels to neural activation. Here we investigated the mechanisms that underlie SCI-induced enhancement of neurovascular transmission in a cutaneous vessel, the rat tail artery. Isometric contractions of arterial segments from T11 spinal cord transected and sham-operated rats were compared 6 wk postoperatively. SCI more than doubled the amplitudes of contractions of arteries in response to moderate frequencies of nerve stimulation (0.1 to 1 Hz). In arteries from SCI rats, but not those from sham-operated rats, the L-type Ca(2+) channel blocker nifedipine (1 μM) reduced the amplitudes of nerve-evoked contractions. Furthermore, while the sensitivity to the agonists phenylephrine (α(1)-adrenoceptor selective) and clonidine (α(2)-adrenoceptor selective) did not differ significantly between arteries from SCI and sham-operated rats, nifedipine had a greater inhibitory effect on contractions to both agents in arteries from SCI rats. Although sensitivity to clonidine was unchanged, SCI selectively reduced the contribution of postjunctional α(2)-adenceptors to nerve-evoked contractions. In arteries from unoperated rats, the L-type channel agonist BAY K 8644 (0.1 μM) produced a similar enhancement of nerve-evoked contraction to that produced by SCI and also selectively reduced the contribution of α(2)-adrenceptors to these responses. Together the findings demonstrate that the SCI-induced enhancement of neurovascular transmission in the rat tail artery can largely be accounted for by an increased contribution of L-type Ca(2+) channels to activation of the vascular smooth muscle.
authors.affiliation: Dept. of Anatomy and Cell Biology, Univ. of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Hussain
authors.initials: H
authors.lastname: Al Dera
authors.forename: Mark D
authors.initials: MD
authors.lastname: Habgood
authors.forename: John B
authors.initials: JB
authors.lastname: Furness
authors.forename: James A
authors.initials: JA
authors.lastname: Brock
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D004730:Endothelium, Vascular / Q000294:innervation / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000294:innervation / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D012867:Skin / Q000098:blood supply* / Q000294:innervation*; D013116:Spinal Cord / Q000098:blood supply; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000502:physiology*; D013565:Sympatholytics / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D013565:Sympatholytics; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000255:Adenosine Triphosphate; D009543:Nifedipine; D003000:Clonidine; D009638:Norepinephrine