Sympathetic Vasoconstriction Is Potentiated in Arteries Caudal but Not Rostral to a Spinal Cord Transection in Rats

Abstract

Sympathetic nerve-mediated contractions of mesenteric and tail arteries controlled by preganglionic neurones decentralized by a spinal cord injury (SCI) are potentiated, and likely contribute to autonomic dysreflexia. However, reactivity to the α(1)-adrenoceptor agonist phenylephrine has been reported to be enhanced in vascular beds controlled by preganglionic neurones lying both rostral and caudal to an SCI in vivo. Here responses of isometrically-mounted median and saphenous arteries isolated from rats 2 and 8 weeks after transection of the T4 spinal cord have been compared with those from sham-operated rats. After SCI, contractions of median arteries to perivascular nerve stimulation, to α-adrenoceptor agonists (phenylephrine and clonidine), to the P2X-purinoceptor agonist α,β-methylene ATP, and to 60 mM K(+) were unchanged. Blockade of nerve-evoked contractions by α-adrenoceptor antagonists (prazosin and idazoxan) was not affected by SCI in either the median or saphenous arteries. In contrast, at 2 and 8 weeks after SCI, nerve-evoked contractions of saphenous arteries were potentiated. Saphenous arteries were less sensitive to phenylephrine 8 weeks after SCI, and their contractions to 60 mM K(+) were reduced. However, the sensitivity of saphenous arteries to clonidine was unchanged by SCI. Eight weeks after SCI, the reactivity of saphenous arteries to α,β-methylene ATP was unchanged, but the P2-antagonist suramin produced more blockade of nerve-evoked contractions. These findings demonstrate that neurovascular transmission is enhanced in arteries located caudal, but not rostral, to a spinal transection. In the saphenous artery, the most likely explanation seems to be an increase in neurotransmitter release, as may occur in other inactive sympathetic pathways caudal to the lesion.

Autonomic Consequences of Spinal Cord Injury

“…Interestingly, some studies have challenged the concept of α-AR hypersensitivity by reporting no change in pressor response to norepinephrine in rats with complete cervical SCI (216,268), suggesting that apparent enhanced sympathetic response may be caused by periodic episodes of SPN hyperactivity rather than denervation-related hypersensitivity. Other studies have otherwise shown that arterial and venous blood vessels from rats with more chronic SCI markedly increase nerve-evoked constrictions (290,337), and the arterial vascular muscle is transiently supersensitive to α 1 and α 2 -AR agonists (338).…”

Somatosympathetic Vasoconstrictor Reflexes in Human Spinal Cord Injury: Responses to Innocuous and Noxious Sensory Stimulation below Lesion

“…It is common for midthoracic lesions and above (>T6, i.e., above the level of sympathetic outflow to the splanchnic circulation), where many vascular beds may have been decentralized and the only means available to offset the hypertension is to slow down the heart via the vagus nerve (which, because it exits from the base of the skull, is spared in spinal cord injuries). Moreover, denervation supersensitivity of the vessels has been documented in human SCI, such that vascular responses to noradrenaline are greatly exaggerated (Mathias et al, 1976; Arnold et al, 1995), and work in spinalized rats has shown that neurovascular transmission is potentiated (Brock et al, 2006; Rummery et al, 2010). …”

“…It is quite possible that the spinally mediated increase in sympathetic outflow to somatosensory stimulation following SCI is exaggerated: we know that the duration of the cutaneous vasoconstriction is increased in human SCI (Brown et al, 2007, 2009a), but this may well reflect an augmented peripheral – as opposed to central – response. Indeed, in the spinal rat blood vessels show an increased reactivity to direct stimulation of the vasomotor nerves (Yeoh et al, 2004a,b; Brock et al, 2006; McLachlan and Brock, 2006; Rummery et al, 2010). It is now believed that neurovascular transmission is potentiated by both an increase in neurotransmitter release and a reduction in noradrenaline reuptake, depending on the vessel (Brock et al, 2006; McLachlan, 2007; Rummery et al, 2010).…”

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

“…These bursts were associated with reductions in skin blood flow that were prolonged relative to those in able-bodied subjects, suggesting that a more important change may be that the vasculature caudal to a spinal lesion becomes hyperresponsive to sympathetic activity (see also Ref. 7).In support of this suggestion, recent studies (6,30,43) in rats have demonstrated that chronic SCI produces a large enhancement of neurovascular transmission in arteries supplying the cutaneous and splanchnic vascular beds. As the effects of SCI in rat tail artery, which supplies blood to the skin of tail, were similar to those observed when its supplying postganglionic neurons were decentralized (by transecting their preganglionic inputs; Ref.…”