Regional haemodynamic effects of adenosine in normal and lipopolysaccharide-treated rats

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

Adenosine (ADO)-mediated vasodilatations play an important role in the maintenance of regional perfusion during sepsis (Motew et al., 1998), but whether or not vascular sensitivity to ADO is affected in this condition is not known. We have now assessed regional haemodynamic responses to ADO in normal and lipopolysaccharide (LPS)-treated rats.

Under anaesthesia (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, least 10 days later, catheters implanted in the jugular vein, peritoneal cavity and the distal aorta. Experiments began at least 24h after catheter implantation in conscious, unrestrained animals. In the same animals (n=11), cardiovascular responses to 3 min infusions of ADO (300μg kg-1 min-1 i.v.) were assessed 1.5h and 6h after saline (0.5 ml i.p.) on Day 1, and after LPS-treatment (E.coli serotype 0127:B8, Sigma, 1mg kg-1 i.p.) on Day 3.

In saline-treated rats, ADO caused significant (P<0.05, Friedman’s test) tachycardia, hypotension and widespread vasodilatation (Table 1). At 1.5h after LPS-treatment, the tachycardic and renal vasodilator effects of ADO were abolished but there was no change in the mesenteric or hindquarters responses (Table 1). At 6h after LPS, there was some return of the tachycardic and renal vasodilator responses to ADO, but a complete loss of the vasodilator response in the hindquarters.



Table 1: Cardiovascular variables before (0), and changes (Δ) after 3 min infusions of ADO 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).

Reduced ADO-mediated vasodilatation following LPS may be explained by either enhanced A1 receptor-mediated vasoconstrictor responses, and/or impaired A2 receptor-mediated vasodilator responses.

Motew SJ et al. (1998) J Surg Res 80 : 326-332

Research supported by a British Heart Foundation grant