| pA2
online © Copyright 2003 The British Pharmacological Society |
024P
University
of Manchester Autumn Meeting September 2003 |
| Haemodynamic effects of noradrenaline (NA) infusion in conscious rats treated with lipopolysaccharide (LPS)
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In endotoxaemia, impaired in vitro responsiveness to vasoconstrictors may be apparent when the agonist is administered by infusion but not by bolus injection, because the response to the former is not sustained (Farmer et al., 2003). We reported normal responses to bolus injection of NA after 24h LPS infusion in vivo (Tarpey et al., 1998). Here we assessed responsiveness to 3min i.v. infusions of NA (750 ng kg-1 min-1) in male Sprague-Dawley rats receiving continuous i.v. saline (0.4 ml h-1, n=8) or LPS (E coli serotype 0127:B8, 150 µg kg-1 h-1, n=8). Under anaesthesia (fentanyl and medetomidine, 300 µg kg-1 of each i.p.), rats (400-480g) had pulsed Doppler flow probes and, intravascular catheters implanted in a two-stage procedure, separated by at least 14 days. On the day following catheterisation, measurements of heart rate (HR), mean arterial blood pressure (MBP) and renal (R), mesenteric (M), and hindquarters (H) vascular conductance (VC) were made in conscious animals. Responses to NA are shown in Table 1.
|
Saline
2h
|
Saline
24h
|
|||||
|
1min
|
2min
|
3min
|
1min
|
2min
|
3min
|
|
| HR |
-62±13*
|
-51±15*
|
-53±10*
|
-53±10*
|
-41±11*
|
-44±9*
|
| MBP |
+35±4*
|
+52±3*
|
+55±3*
|
+40±5*
|
+58±4*
|
+58±4*
|
| RVC |
-53±2*
|
-56±2*
|
-58±1*
|
-54±4*
|
-59±3*
|
-58±3*
|
| MVC |
-41±4*
|
-48±3*
|
-49±3*
|
-38±6*
|
-49±3*
|
-50±3*
|
| HVC |
-27±5*
|
-32±5*
|
-34±4*
|
-29±7*
|
-30±3*
|
-36±3*
|
|
LPS
2h
|
LPS
24h
|
|||||
| HR |
-4±14
|
-9±14
|
-4±13
|
-4±8
|
+1±13
|
-8±17
|
| MBP |
+11±1*
|
+13±2*
|
+10±2*
|
+20±3*
|
+24±4*
|
+26±4*
|
| RVC |
-17±1*
|
-19±2*
|
-14±3*
|
-31±3*
|
-33±4*
|
-32±5*
|
| MVC |
-13±3*
|
-10±4*
|
-5±5*
|
-31±4*
|
-34±5*
|
-32±5*
|
| HVC |
-2±4
|
-6±5
|
-2±3
|
-17±4*
|
-23±6*
|
-24±5*
|
Table
1. Changes (mean ± s.e.mean) in HR (beats min-1),
MBP (mmHg), RVC, MVC and HVC (%) during 3 min infusions of NA in rats
infused with saline (n=8) or LPS (n=8). * P 
0.05
vs baseline (Friedman's test).
After
2h LPS infusion, MAP was normal but the pressor and vasoconstrictor responses
to NA (0-3min areas) were less (P0.05,
Mann-Whitney) than in the presence of saline and there was no bradycardia.
After 24h LPS infusion, MAP was still normal, there was still no bradycardia
to NA, but the other cardiovascular responses were greater (P0.05,
Wilcoxon) than at 2h although, except for the fall in HVC, still less
(P0.05) than
in the presence of saline. Thus, the diminished effects of NA infusion
in LPS-treated rats is not due to a rapid waning of the response, unlike
the in vitro observations (Farmer et al., 2003). A notable feature
of the present results is the lack of a consistent bradycardic response
to NA infusion in LPS-treated rats, in contrast to the significant fall
in HR seen with bolus injection of NA (Tarpey et al., 1998).
This work was supported by the Anaesthetic Research SocietyFarmer.
M.R.
et al. (2003) J. Pharmacol. Exp. Ther., 306, 538-545.
Tarpey, S.B. et al. (1998). Br. J. Pharmacol., 123,
332P.