Spinal cord injury increases the reactivity of rat tail artery to angiotensin II

Abstract

Studies in individuals with spinal cord injury (SCI) suggest the vasculature is hyperreactive to angiotensin II (Ang II). In the present study, the effects of SCI on the reactivity of the rat tail and mesenteric arteries to Ang II have been investigated. In addition, the effects of SCI on the facilitatory action of Ang II on nerve-evoked contractions of these vessels were determined. Isometric contractions of artery segments from T11 (tail artery) or T4 (mesenteric arteries) spinal cord-transected rats and sham-operated rats were compared 6-7 weeks postoperatively. In both tail and mesenteric arteries, SCI increased nerve-evoked contractions. In tail arteries, SCI also greatly increased Ang II-evoked contractions and the facilitatory effect of Ang II on nerve-evoked contractions. By contrast, SCI did not detectably change the responses of mesenteric arteries to Ang II. These findings provide the first direct evidence that SCI increases the reactivity of arterial vessels to Ang II. In addition, in tail artery, the findings indicate that Ang II may contribute to modifying their responses following SCI.

Keywords: angiotensin II; neurovascular transmission; spinal cord injury; sympathetic nerves; vascular reactivity.

Figure 1

Spinal cord injury (SCI) increased nerve-evoked contractions of both tail and mesenteric arteries. (A) Representative traces showing contractions of a tail artery segment from a sham-operated (black trace) and a SCI (red trace) rat evoked by 25 stimuli at 0.1, 0.3, 0.5, and 1 Hz. (B) Peak increases in wall tension produced by these trains of stimuli in tail arteries from sham-operated (white bars, n = 8) and SCI (red bars, n = 8) rats. (C) Representative traces showing contractions of a mesenteric artery segment from a sham-operated (black trace) and a SCI (red trace) rat evoked by 100 stimuli at 1, 3, 5, 10, and 20 Hz. (D) Peak increases in wall tension produced by these trains of stimuli in mesenteric arteries from sham-operated (white bars, n = 7) and SCI (red bars, n = 6) rats. In (B,D), the data are presented as a mean and SE with statistical differences between control and SCI arteries indicated by asterisks (unequal variance t-test; ^*P < 0.05, ^**P < 0.01).

Figure 2

Spinal cord injury (SCI) increased the responsiveness of tail arteries to angiotensin II (Ang II). (A,B) Concentration–contraction curves for Ang II (1–100 nM) in tail arteries (A) and mesenteric arteries (B) from sham-operated (open circles; tail artery n = 8, mesenteric artery n = 7) and SCI rats (solid red circles; tail artery n = 8, mesenteric artery n = 6). In (A), the data are presented as mean and SE and statistical comparisons between the summed data for sham-operated and SCI arteries was made with a unequal variance t-test (P indicated in A). In (B), the data are present as median and interquartile range and statistical comparison between the summed data for sham-operated and SCI arteries groups was made with an Mann–Whitney U-test (P indicated in B).

Figure 3

Angiotensin II (Ang II) increased nerve-evoked contractions of both tail arteries and mesenteric arteries. In tail arteries, but not mesenteric arteries, the increment in the size of nerve-evoked contractions produced by Ang II was markedly increased by spinal cord injury (SCI). (A) Representative traces showing contractions of tail artery segments from a sham-operated (left panel) and a SCI (right panel) rat evoked by 5 stimuli at 0.5 Hz before and during application of 1, 10, and 100 nM Ang II. (B) Representative traces showing contractions of mesenteric artery segments from a sham-operated (left panel) and a SCI (right panel) rat evoked by 20 stimuli at 10 Hz before and during application of 1, 10, and 100 nM Ang II. (C,D) The increment in the size of nerve-evoked contractions produced by Ang II (1–100 nM) in tail arteries (C) and mesenteric arteries (D) from sham-operated (open circles; tail artery n = 8, mesenteric artery n = 7) and SCI (solid red circles; tail artery n = 8, mesenteric artery n = 6) rats. The “zero” Ang II data is for time-matched controls with no Ang II added. In (C,D), the data are present as mean and SE and statistical comparisons between the curves were made by comparing the summed data for sham-operated and SCI arteries using unequal variance t-tests (P indicated in C,D).

Figure 4

The angiotensin II (Ang II) type 1 receptor antagonist losartan (100 nM) blocked both Ang II-evoked contractions and the enhancement of nerve-evoked contractions produced by Ang II in tail arteries and mesenteric arteries from sham-operated and spinal cord injured (SCI) rats. On its own losartan did not change nerve-evoked contractions. (A,B) Peak increases in wall tension produced by 100 nM Ang II in tail arteries (A; sham-operated n = 8, SCI n = 8) or mesenteric arteries (B; sham-operated n = 7, SCI n = 6) in the absence (white bars) or in the presence (red bar) of losartan. (C,D) Peak increases in wall tension evoked by nerve stimulation (tail artery: 5 stimuli at 0.5 Hz; mesenteric artery: 20 stimuli at 10 Hz) before (white bar) and during (red bar) application of losartan in tail arteries (C; sham-operated n = 6, SCI n = 6) and mesenteric arteries (D; sham-operated n = 7, SCI n = 6). (E) The increment in the size of nerve-evoked contractions produced by 100 nM Ang II in tail arteries in the absence (white bars; sham-operated n = 7, SCI n = 7) or in the presence (red bars; sham-operated n = 7, SCI n = 7) of losartan. (F) The increment in the size of nerve-evoked contrations produced by 1 nM Ang II in mesenteric arteries (sham-operated n = 7, SCI n = 6) in the absence (white bars) or in the presence (red bars) of losartan. Data are presented as median and interquartile in (A,B) and mean and SE in (C–F). Statistical differences between responses in the absence and in the presence of losartan are indicated by asterisks (by Mann–Whitney U-tests (in A,B) or unequal variance t-tests (in E,F); ^*P < 0.05, ^**P < 0.01).