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© Copyright 2004 The British Pharmacological Society

034P University of Bath
Summer Meeting July 2004

Effects of propranolol on the haemodynamic responses to lipopolysaccharide (LPS) infusion in conscious rats

T Bennett, J E March, P A Kemp & S M Gardiner, School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, UK

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Bennett T
March JE
Kemp PA
Gardiner SM

Catecholamines may be involved in the cardiovascular sequelae of sepsis either directly, or indirectly, by affecting pro- and anti-inflammatory mediator production (Haskó & Szabó, 1998), for example. We have now assessed the influence of the ß-adrenoceptor antagonist, propranolol, given before, or at the end of, a 24h infusion of LPS.

Under anaesthesia (fentanyl and medetomidine, 300 µg kg-1 of each i.p.), male Sprague-Dawley rats (400-480g) had pulsed Doppler flow probes (renal (R), mesenteric (M), distal aortic (hindquarters (H))) and catheters (distal aorta, jugular vein) implanted in a 2-stage procedure separated by at least 10 days. Twenty four h after the last procedure (catheterisation), mean arterial blood pressure (BP), heart rate (HR), and R, M and H vascular conductances (VC) were measured in conscious animals, before and during 24h i.v. infusion of LPS (150 µg kg-1 h-1, E coli serotype 0127 B8), in the presence of saline (0.4 ml h-1, n=8) or propranolol (1 mg kg-1, 0.5 mg kg-1 h-1, n=8). A third group (n=7) was given propranolol at the end of 24h infusion of LPS. Some results are in Table 1.

Table 1. Changes in cardiovascular variables in rats treated with saline (A) or propranolol either before (B) or at the end of (C) 24h infusion of LPS. Values are mean ± s.e. mean. * P 0.05 vs before LPS, † P 0.05 vs 24h value (Friedman’s test).

Time after start of LPS (h)

1.25
1.75
6
24
24.25
HR (beats min-1)
A
+107 ± 9*
+88 ± 13*
+103 ± 9*
+96 ± 15*
+89 ± 15*
 

B

+37 ± 12
+29 ± 9
+75 ± 11*
+32 ± 14
+28 ± 15
 
C
+115 ± 11*
+100 ± 11*
+103 ± 13*
+83 ± 13*
+47 ± 10*†
BP (mmHg)
A
-15 ± 4*
+1 ± 4
+11 ± 5*
+3 ± 5
+3 ± 5
 
B
-1 ± 3
+2 ± 4
-5 ± 6
-2 ± 5
-3 ± 5
 

C
-17 ± 4*
+5 ± 2
+13 ± 6*
+4 ± 5
+7 ± 6

RVC (%)

A
+43 ± 11*
+43 ± 14*
+39 ± 7*
+53 ± 12*
+58 ± 12*
 
B
+30 ± 4*
+32 ± 9*
+58 ± 13*
+34 ± 9*
+39 ± 11*
 

C

+41 ± 10*
+36 ± 11*
+49 ± 19*
+52 ± 18*
+45 ± 20*

HVC (%)

A
+70 ± 5*
+13 ± 6
+5 ± 10
+68 ± 15*
+70 ± 16*
 
B
+15 ± 14
-5 ± 5
-18 ± 6*
+12 ± 9
+13 ± 9
 

C

+71 ± 8*
+17 ± 8
+7 ± 4
+65 ± 17*
+35 ± 16*†

In the presence of saline, LPS infusion caused short-lived hypotension, tachycardia, persistent renal vasodilatation, biphasic hindquarters vasodilatation (Table 1) but variable changes in MVC (not shown). Pre-treatment with propranolol prevented the hypotension, and increases in HVC caused by LPS, whereas propranolol given after 24h of LPS infusion reduced, but did not abolish, the increase in HVC. Likewise, in LPS-infused animals pre-treated with propranolol, there was no tachycardia at 24h whereas propranolol administered after 24h of LPS infusion reduced, but did not abolish the tachycardia. It is feasible that pre-treatment with propranolol inhibits mechanisms in addition to direct ß-adrenoceptor-mediated cardiovascular events, which influence the cardiovascular sequelae in sepsis.

Haskó, G. & Szabó, C. (1998). Biochem. Pharmacol., 56, 1079-1087