Spinal cord injury disrupts regulation of arterial pressure, often resulting in episodic hypertension initiated by spinal reflexes. The contribution of spinally generated sympathetic nerve activity (SNA) to control of resting arterial pressure after cord injury is questionable. The mechanisms responsible for the reflex hypertension also are unresolved. One important question concerns whether or not this hypertension is caused by large spinal sympathetic reflexes or by the known increased vascular sensitivity to norepinephrine and limited effectiveness of baroreceptor reflexes that occur after spinal cord injury. We evaluated the relationship between renal SNA and mean arterial pressure (MAP) in basal conditions and during reflex pressor responses induced by colon distension in conscious rats for 1 wk after midthoracic spinal cord transection (SCT). One day after SCT, MAP (69 +/- 6 mmHg) and SNA(6 +/- 2 microV x s) were lower than the MAP (92 +/- 4 mmHg) and SNA (18 +/- 3 microV x s) in the same anesthetized rats before SCT. At 6 days, MAP increased to 94 +/- 6 mmHg, whereas SNA remained low (4 +/- 1 microV x s). One day after SCT, colon distension increased MAP by 28 +/- 4 mmHg and SNA by 35 +/- 6 microV x s; these responses remained unchanged for 6 days. These data suggest that spinally generated SNA makes no apparent contribution to basal MAP. In contrast, afferent stimulation can produce large excitatory spinal sympathetic reflexes that appear adequate to cause substantial increases in arterial pressure.

The neurotransmitters mediating the spinal sympathetic reflexes that initiate episodic hypertension after spinal cord injury are unknown. We examined the role of glutamatergic transmission in these reflexes by testing effects of the N-methyl-D-aspartate (NMDA)-receptor antagonist 2-amino-5-phosphonopentanoic acid (AP-5) and of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzoquinone (NBQX) on the reflex hypertension caused by colon distension. Antagonists were administered intrathecally in conscious rats 1-2 days (acute, n = 10) or 15-16 days (chronic, n = 14) after cord transection at the fifth thoracic segment under barbiturate anesthesia. AP-5 blocked pressor responses to intrathecal NMDA but had no effect on responses to AMPA; similarly, NBQX blocked responses to AMPA but had no effect on responses to NMDA. Before antagonist injection, colon distension increased mean arterial pressure by 24 +/- 1 mmHg (from 100 +/- 3 mmHg) and by 37 +/- 2 mmHg (from 116 +/- 3 mmHg) in the acute and chronic groups, respectively. Pretreatment with AP-5 attenuated the pressor responses by 36 and 37% in these respective groups; pretreatment with NBQX attenuated them by 34 and 31%. These data suggest that both NMDA and AMPA receptors contribute to spinal viscerosympathetic transmission and initiation of episodic hypertension in conscious spinal rats.

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Abnormal sympathetic tone after spinal cord injury (SCI) initially results in hypotension and is subsequently associated with autonomic dysreflexia characterized by paroxysmal hypertension and bradycardia in response to noxious or visceral stimuli. To evaluate the effect of a clinically relevant compression model of SCI on cardiovascular control in the early postinjury period, we monitored arterial pressure (AP) and heart rate under control resting conditions and after visceral stimulation (colon distension) in conscious rats for 1 week after clip compression injury of the cord at T5. Rats were randomly allocated into 4 groups (n = 8 each): sham-operated, 20, 35, and 50 g injuries. Only the 50 g injury was associated with significant hypotension (73 +/- 4 mmHg) at 1 day post-SCI when compared to sham-injured rats (91 +/- 3 mmHg). In control rats, colon distention caused a transient pressor response of 16 +/- 3 mmHg and tachycardia. In rats with 20 g 35 g, and 50 g injuries, colon distension 1 day after SCI increased AP by 8 +/- 2, 15 +/- 3, and 21 +/- 1 mmHg, respectively. The hypertensive response correlated with injury severity (r = 0.75; p < 0.0001) and was associated with bradycardia. By 7 days after SCI, only rats with 50 g cord injuries experienced hypertension with reflex bradycardia with visceral stimulation. These data show that dysfunctional cardiovascular control after SCI is correlated with the severity of injury. Mild and moderate compressive SCI result in transient cardiovascular abnormalities which normalize by 1 week. In contrast, more severe injuries are associated with neurogenic hypotension and autonomic dysreflexia.

The effects of inhibiting the neural activity in the pontine A5 region on renal sympathetic responses to baroreflex and/or chemoreflex activation were examined in conscious rabbits. Eight rabbits were chronically instrumented with guide cannulas for bilateral microinjections into the A5 area and an electrode for measuring renal sympathetic nerve activity (RSNA). Baroreflex curves were obtained under conditions of normoxia and hypoxia (10% O(2) + 3% CO(2)) after injections into the A5 region of the GABA receptor agonist muscimol or vehicle solution. Under normoxia, injections of muscimol did not affect resting RSNA or blood pressure but increased the range of the RSNA baroreflex by 24 and 33% at doses of 175 or 875 pmol, respectively, without affecting the reflex gain. Hypoxia alone increased resting RSNA by 63%, as well as the range and gain of the RSNA baroreflex by 53 and 89%, respectively, without affecting blood pressure. However, under hypoxia, muscimol increased resting RSNA by 37 and 47% but decreased the gain of the RSNA baroreflex by 19 and 34% at doses of 175 or 875 pmol, respectively, without affecting the reflex range. The effects of muscimol on RSNA were mediated via changes in the amplitude of the sympathetic bursts, whereas burst frequency remained unaffected. These data suggest that the A5 region has a little tonic influence on RSNA in conscious rabbits but serves to limit the renal sympathetic responses to baroreceptor unloading or chemoreceptor stimulation. The different changes in the baroreflex range and gain evoked by muscimol under normoxia and hypoxia indicate that the A5 modulatory action may depend on the activity of the afferent inputs to this region.