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.

Mangiferin attenuates contusive spinal cord injury in rats through the regulation of oxidative stress, inflammation and the Bcl-2 and Bax pathway

“…Oxidative stress is a basic protective mechanism of the body, which is involved in the regulation of life activities, including cell signal transduction, cell proliferation and apoptosis (21). Mitochondrial dysfunction is an important factor leading to nerve cell death following SCI, which is directly associated with substantial accumulation of Ca 2+ in the cells following injury (22). Oxidative stress following SCI damages ion homeostasis inside and outside the membrane, and a large quantity of Ca 2+ enters into the mitochondria, accumulating inside and causing damage to mitochondria, which leads to aerobic energy metabolism, inhibiting the synthesis of ATP (23).…”

Plasticity of TRPV1-Expressing Sensory Neurons Mediating Autonomic Dysreflexia Following Spinal Cord Injury

“…For complete lesions above T5/6, SCI is almost always accompanied by cardiovascular disturbances including orthostatic hypotension (OH; a sudden fall in blood pressure upon assuming an upright position) and autonomic dysreflexia (AD; potentially life-threatening elevations in blood pressure triggered by sensory stimulation below the injury; Krassioukov and Claydon, 2006). There is increasing evidence that blood vessels, a peripheral target of sensory as well as sympathetic axons, also undergo SCI-induced alterations which may evoke phenotypic changes in their innervating neurons (McLachlan and Brock, 2006; Alan et al, 2010; Rummery et al, 2010; Al Dera et al, 2011; Tripovic et al, 2011). …”

Angiotensin II system in the nucleus tractus solitarii contributes to autonomic dysreflexia in rats with spinal cord injury

“…The underlying mechanisms still have not been well explicated. Current explanation to hypertension induced by AD is mostly focused on the peripheral system, such as that the elevated tonic activity of arterial smooth muscles and malfunction of the nerve conduction in spinal level[32–34]. It is rarely accepted that the central nervous system might play a role in AD, because seemingly sensory information cannot be transmitted from the site of irritation (for example, the colon) to the brainstem, if the spinal cord is completely transected.…”