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Regional haemodynamic responses to adenosine receptor activation vary across time following lipopolysaccharide treatment in conscious rats.

ABSTRACT: Studies using adenosine receptor antagonists have shown that adenosine-mediated vasodilatations play an important role in the maintenance of regional perfusion during sepsis, but it is unclear whether vascular sensitivity to adenosine is affected. Here, we assessed regional haemodynamic responses to adenosine agonists and antagonists in normal and lipopolysaccharide (LPS)-treated rats to investigate a possible role for adenosine in the haemodynamic sequelae.Male Sprague-Dawley rats were chronically instrumented with pulsed Doppler flow probes to measure regional haemodynamic responses to adenosine-receptor agonists (adenosine, 2-choloro-N6-cyclopentyladenosine (CCPA)) and antagonists (8-phenyltheophylline (8-PT), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)), at selected time points in control and LPS-treated rats.The responses to 8-PT were consistent with endogenous adenosine causing bradycardia, and renal and hindquarters vasodilatation in control rats, whereas in LPS-treated rats, there was evidence for endogenous adenosine causing renal (at 1.5 h) and hindquarters (at 6 h) vasoconstriction. In control animals, exogenous adenosine caused hypotension, tachycardia and widespread vasodilatation, whereas in LPS-treated rats, the adenosine-induced renal (at 1.5 h) and hindquarters (at 6 h) vasodilatations were abolished. As enhanced A1 receptor-mediated vasoconstriction could explain the results in LPS-treated rats, vascular responsiveness to a selective A1-receptor agonist (CCPA) or antagonist (DPCPX) was assessed. There was no evidence for enhanced vasoconstrictor responsiveness to CCPA in LPS-treated rats, but DPCPX caused renal vasodilatation, consistent with endogenous adenosine mediating renal vasoconstriction under these conditions.The results show changes in adenosine receptor-mediated cardiovascular effects in endotoxaemia that may have implications for the use of adenosine-based therapies in sepsis.

SUBMITTER: Jolly L

PROVIDER: S-EPMC2440086 | biostudies-other | 2008 Aug

REPOSITORIES: biostudies-other

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Project description:Research has shown that inflammatory processes affect brain function and behavior through several neuroimmune pathways. However, high order brain functions affected by inflammation largely remain to be defined. Resting state functional connectivity of synchronized oscillatory activity is a valid approach to understand network processing and high order brain function under different experimental conditions. In the present study multi-electrode EEG recording in awake, freely moving rats was used to study resting state connectivity after administration of lipopolysaccharides (LPS). Male Wistar rats were implanted with 10 cortical surface electrodes and administered with LPS (2 mg/kg) and monitored for symptoms of sickness at 3, 6 and 24 h. Resting state connectivity and power were computed at baseline, 6 and 24 h. Three prominent connectivity bands were identified using a method resistant to spurious correlation: alpha (5-15 Hz), beta-gamma (20-80 Hz), and high frequency oscillation (150-200 Hz). The most prominent connectivity band, alpha, was strongly reduced 6 h after LPS administration, and returned to baseline at 24 h. Beta-gamma connectivity was also reduced at 6 h and remained reduced at 24 h. Interestingly, high frequency oscillation connectivity remained unchanged at 6 h and was impaired 24 h after LPS challenge. Expected elevations in delta and theta power were observed at 6 h after LPS administration, when behavioral symptoms of sickness were maximal. Notably, gamma and high frequency power were reduced 6 h after LPS and returned to baseline by 24 h, when the effects on connectivity were more evident. Finally, increases in cross-frequency coupling elicited by LPS were detected at 6 h for theta-gamma and at 24 h for theta-high frequency oscillations. These studies show that LPS challenge profoundly affects EEG connectivity across all identified bands in a time-dependent manner indicating that inflammatory processes disrupt both bottom-up and top-down communication across the cortex during the peak and resolution of inflammation.

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Regional haemodynamic responses to adenosine receptor activation vary across time following lipopolysaccharide treatment in conscious rats.

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