092P Brighton
Winter Meeting December 2007



Adenosine A1 receptor-mediated haemodynamic responses in normal and lipopolysaccharide (LPS)-treated rats


Lisa Jolly, Julie March, Philip Kemp, Terence Bennett, Sheila Gardiner
University of Nottingham, Nottingham, United Kingdom


We hypothesised (Jolly et al., this meeting) that reduced adenosine-mediated vasodilatation following LPS treatment could be explained by either enhanced A1 receptor-mediated vasoconstrictor responses, or impaired A2 receptor-mediated vasodilator responses. We have now assessed vascular responsiveness to the A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA) before and after treatment with LPS.

Anaesthetised (fentanyl and medetomidine 300μg kg-1 of each i.p.), male Sprague-Dawley rats (400-500g) had pulsed Doppler flow probes implanted to measure renal (R), mesenteric (M) and hindquarters (H) blood flows, and, at least 10 days later, catheters implanted in the jugular vein, peritoneal cavity and distal aorta. Experiments began at least 24h after catheter implantation. Cardiovascular responses to 3 min infusions of CCPA (1.4μg kg-1 min-1 i.v.) were assessed either 1.5h (n=8) or 6h (n=8) after saline (0.5 ml i.p.) on Day 1 and LPS (E.coli serotype 0127:B8, 1mg kg-1 i.p.) on Day 3.

In saline-treated rats CCPA caused significant (P<0.05, Friedman’s test) bradycardia, hypotension, renal and mesenteric vasoconstriction and hindquarters vasodilatation (Table 1). At 1.5h after LPS treatment, CCPA caused greater bradycardia, smaller hypotension and no mesenteric vasoconstriction, whereas at 6h after LPS treatment, the bradycardic and renal and mesenteric vasoconstrictor responses to CCPA were greater than in the saline-treated condition (Table 1).

Table 1: Cardiovascular variables before (0) and changes (Δ) after 3 min CCPA infusions in saline- and LPS-treated rats. Values are mean ± s.e.m. Units are heart rate (HR) beats min-1; mean arterial blood pressure (MAP) mmHg; vascular conductance (VC) (kHz mmHg-1)103 at baseline (0) and % Δ. *P<0.05 vs corresponding value in saline-treated rats (Wilcoxon Test).
1.5h 6h
Saline LPS Saline LPS
0 Δ 0 Δ 0 Δ 0 Δ
HR 336±6 -131±8 385±8* 172±12* 360±11 -75±11 416±6* 100±13*
MAP 110±2 -28±3 108±5 -16±3* 111±3 -7±1 99±3 -5±2
RVC 94±5 -45±4 109±7 -47±6 75±8 -29±3 98±11* -35±4*
MVC 66±5 -19±5 50±9 +4±4* 70±8 -21±3 106±1* -32±2*
HVC 45±5 +38±8 52±6 +28±6 42±5 +26±5 53±5* +23±8



These results show that enhanced A1 receptor-mediated vasoconstriction cannot explain the loss of adenosine-induced renal vasodilatation (at 1.5h after LPS) and hindquarters vasodilatation (at 6h after LPS) reported previously (Jolly et al., this meeting). Whether or not these can be explained by changes in A2 receptor-mediated vasodilatation remains to be determined.

Research supported by a British Heart Foundation grant.