An increased contribution of L-type Ca2+ channels to activation of vascular muscle underlies spinal cord injury-induced augmentation of neurovascular transmission in rat tail artery

2011 ◽  
Vol 163 (1-2) ◽  
pp. 69
Author(s):  
H.S. Al Dera ◽  
M.D. Habgood ◽  
J.B. Furness ◽  
J.A. Brock
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Tail Artery ◽  
Tail Artery ◽  
Vascular Muscle ◽  
Cord Injury ◽  
Ca2 Channels ◽  
Rat Tail ◽  
Neurovascular Transmission

Prominent contribution of L-type Ca2+ channels to cutaneous neurovascular transmission that is revealed after spinal cord injury augments vasoconstriction

2012 ◽  
Vol 302 (3) ◽  
pp. H752-H762 ◽  
Author(s):  
Hussain Al Dera ◽  
Mark D. Habgood ◽  
John B. Furness ◽  
James A. Brock
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inhibitory Effect ◽  
Neural Activation ◽  
Rat Tail Artery ◽  
Tail Artery ◽  
Cord Injury ◽  
Evoked Contractions ◽  
Rat Tail ◽  
Neurovascular Transmission

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 Ca2+ channel blocker nifedipine (1 μM) reduced the amplitudes of nerve-evoked contractions. Furthermore, while the sensitivity to the agonists phenylephrine (α1-adrenoceptor selective) and clonidine (α2-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 α2-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 α2-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 Ca2+ channels to activation of the vascular smooth muscle.

Quercetin antagonism of Bay K 8644 effects on rat tail artery L-type Ca2+ channels

2008 ◽  
Vol 598 (1-3) ◽  
pp. 75-80 ◽  
Author(s):  
Simona Saponara ◽  
Giampietro Sgaragli ◽  
Fabio Fusi
Keyword(s):  
Bay K 8644 ◽  
Rat Tail Artery ◽  
Tail Artery ◽  
Ca2 Channels ◽  
Rat Tail

Nitroglycerin relaxes rat tail artery primarily by lowering Ca2+ sensitivity and partially by repolarization

1996 ◽  
Vol 271 (3) ◽  
pp. H962-H968 ◽  
Author(s):  
X. L. Chen ◽  
C. M. Rembold
Keyword(s):  
Smooth Muscle ◽  
Isometric Force ◽  
Rat Tail Artery ◽  
Tail Artery ◽  
Cyclic Monophosphate ◽  
Physiological Relevance ◽  
Strain Gauge Transducer ◽  
K Concentration ◽  
Ca2 Channels ◽  
Rat Tail

At least five mechanisms are hypothesized to account for guanosine 3',5'-cyclic monophosphate (cGMP)-induced relaxation of arterial smooth muscle: 1) repolarization, 2) inhibition of Ca2+ release, 3) inactivation of L-type Ca2+ channels, 4) enhancement of Ca2+ efflux/sequestration, and 5) decreasing the intracellular Ca2+ concentration ([Ca2+]i) sensitivity of force. The goal of this study was to investigate the physiological relevance of these five mechanisms in the intact rat tail artery. We stimulated deendothelialized rat tail artery with phenylephrine or high extracellular K+ concentration ([K+]o) and then relaxed the tissue by adding nitroglycerin to increase guanosine 3',5'-cyclic monophosphate concentration. We measured membrane potential (Em) with microelectrodes, [Ca2+]i with fura 2, and isometric force with a strain-gauge transducer. We found that decreases in the [Ca2+]i sensitivity of force accounted for most of the nitroglycerin-induced relaxation of tissues prestimulated with maximal (1 microM) phenylephrine or 30 mM [K+]o. In submaximally (0.1-0.3 microM) phenylephrine-prestimulated tissues, nitroglycerin-induced relaxation was caused primarily by a decrease in the [Ca2+]i sensitivity of force and partially by repolarization and the resultant decrease in [Ca2+]i. Nitroglycerin also partially attenuated transient increases in [Ca2+]i and force induced by 100 microM phenylephrine in the absence of extracellular Ca2+, indicating that nitroglycerin also inhibited intracellular Ca2+ release. Nitroglycerin-induced relaxation was not associated with inactivation of Ca2+ channels or enhancement of Ca2+ efflux/sequestration. These data suggest that nitroglycerin relaxes precontracted rat tail artery primarily by decreasing the [Ca2+]i sensitivity of force.

scholarly journals Spinal cord injury alters purinergic neurotransmission to mesenteric arteries in rats

2020 ◽  
Vol 318 (2) ◽  
pp. H223-H237
Author(s):  
Sutheera Sangsiri ◽  
Hui Xu ◽  
Roxanne Fernandes ◽  
Greg D. Fink ◽  
Heidi L. Lujan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Atp Release ◽  
Mesenteric Arteries ◽  
Cord Injury ◽  
Purinergic Neurotransmission ◽  
Neurovascular Transmission ◽  
Intact Rats

Complications associated with spinal cord injury (SCI) result from unregulated reflexes below the lesion level. Understanding neurotransmission distal to the SCI could improve quality of life by mitigating complications. The long-term impact of SCI on neurovascular transmission is poorly understood, but reduced sympathetic activity below the site of SCI enhances arterial neurotransmission (1). We studied sympathetic neurovascular transmission using a rat model of long-term paraplegia (T2–3) and tetraplegia (C6–7). Sixteen weeks after SCI, T2–3 and C6–7 rats had lower blood pressure (BP) than sham rats (103  ±  2 and 97  ±  4 vs. 117  ±  6 mmHg, P < 0.05). T2–3 rats had tachycardia (410  ±  6 beats/min), and C6–7 rats had bradycardia (299  ±  10 beats/min) compared with intact rats (321  ±  4 beats/min, P < 0.05). Purinergic excitatory junction potentials (EJPs) were measured in mesenteric arteries (MA) using microlectrodes, and norepinephrine (NE) release was measured using amperometry. NE release was similar in all groups, while EJP frequency-response curves from T2–3 and C6–7 rats were left-shifted vs. sham rats. EJPs in T2–3 and C6–7 rats showed facilitation followed by run-down during stimulation trains (10 Hz, 50 stimuli). MA reactivity to exogenous NE and ATP was similar in all rats. In T2–3 and C6–7 rats, NE content was increased in left cardiac ventricles compared with intact rats, but was not changed in MA, kidney, or spleen. Our data indicate that peripheral purinergic, but not adrenergic, neurotransmission increases following SCI via enhanced ATP release from periarterial nerves. Sympathetic BP support is reduced after SCI, but improving neurotransmitter release might maintain cardiovascular stability in individuals living with SCI. NEW & NOTEWORTHY This study revealed increased purinergic, but not noradrenergic, neurotransmission to mesenteric arteries in rats with spinal cord injury (SCI). An increased releasable pool of ATP in periarterial sympathetic nerves may contribute to autonomic dysreflexia following SCI, suggesting that purinergic neurotransmission may be a therapeutic target for maintaining stable blood pressure in individuals living with SCI. The selective increase in ATP release suggests that ATP and norepinephrine may be stored in separate synaptic vesicles in periarterial sympathetic varicosities.

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