Increased nitric oxide in exhaled air of asthmatic patients

BACKGROUNDPreconditioning (5 minutes of ischemia followed by 10 minutes of recovery) renders the heart very resistant to infarction from subsequent ischemia. This study tests whether adenosine receptors might mediate preconditioning protection.METHODS AND RESULTSWe examined the effect on infarct size of pretreatment with either of two adenosine receptor antagonists in both control and preconditioned in situ rabbit hearts. Hearts underwent 30 minutes of regional ischemia plus 3 hours of reperfusion, and infarct size was measured with tetrazolium. Infarct size averaged 39% of the zone at risk in controls but only 8% in preconditioned hearts. Preconditioned and nonpreconditioned hearts receiving either blocker had infarcts not different in size from the controls. A 5-minute intracoronary infusion of adenosine was as effective as 5 minutes of ischemia in protecting parabiotically perfused isolated hearts against infarction from a 45-minute ischemic insult. Similarly, intracoronary infusion of N6-1-(phenyl-2R-...

Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart.

Mammalian nitric oxide synthases.

Adenosine 5'-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation

https://www.jbc.org/content/267/9/6370.full.pdf

Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line.

Generation of nitric oxide by human neutrophils

Differential inhibition of human neutrophil functions. Role of cyclic AMP-specific, cyclic GMP-insensitive phosphodiesterase.

The protein kinase C inhibitors H-7 and H-9 fail to inhibit human neutrophil activation

Adenosine and adenosine receptor agonists have a variety of inhibitory effects on the generation of inflammatory mediators by neutrophils and other cell types. In human neutrophils stimulated with the chemotactic peptide FMLP, adenosine agonists inhibit O2- generation and degranulation. Because these findings suggest that the agonists may have potential as antiinflammatory agents, several compounds were evaluated for effects on the exudative and cellular phases of carrageenan-induced pleural inflammation in rats. All of the agonists tested inhibited both parameters of the inflammatory response. Inhibition appeared to correlate better with binding to the A1 than to the A2 receptor and was reversible by a known adenosine receptor antagonist, 8-phenyltheophylline. In mechanistic studies, R-N-(1-methyl-2-phenylethyl)adenosine, a standard A1 selective agonist, reversed the drop in circulating neutrophil count that occurs after injection of carrageenan. These results suggest that the agonists may prevent cell emigration by inhibiting adhesion to the endothelium or diapedesis. In addition (R)-N-(1-methyl-2-phenylethyl)adenosine had weak inhibitory effects on superoxide production by FMLP-stimulated rat neutrophils. Control studies showed that the effects of the agonists were not the result of agonist-induced hypotension nor corticosterone production by the adrenal glands. These findings indicate that adenosine receptor agonists are effective new pharmacologic tools for the study of inflammatory processes.

Clifford D. Wright

Papers

Generation of nitric oxide by human neutrophils

Differential inhibition of human neutrophil functions. Role of cyclic AMP-specific, cyclic GMP-insensitive phosphodiesterase.

The protein kinase C inhibitors H-7 and H-9 fail to inhibit human neutrophil activation

The antiinflammatory effects of adenosine receptor agonists on the carrageenan-induced pleural inflammatory response in rats.

Characterization of endothelins as chemoattractants for human neutrophils.