COX-inhibiting nitric oxide donors (CINODs): potential benefits on cardiovascular and renal function.
The COX-inhibiting nitric oxide donors (CINODs) are a new class of agents designed for the treatment of pain and inflammation. CINODs have a multi-pathway mechanism of action that involves COX inhibition and nitric oxide donation. The anti-inflammatory and analgesic effects of COX inhibition are reinforced through inhibition of caspase-1 regulated cytokine production, while nitric oxide donation provides multiorgan protection. Whereas both conventional nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2-selective NSAIDs are associated with a variety of adverse effects on the renal system, such as hypertension and edema, CINODs may offer an improved renal safety profile. These agents are devoid of hypertensive effects in animal models and their mechanism of action suggests that they may not cause edema. CINODs also have other renal-sparing effects, being better tolerated than NSAIDs in models of kidney failure. CINODs have been shown to prevent platelet activation in vitro and exhibit anti-thrombotic activity in vivo. In animal models of ischemia/reperfusion, CINODs treatment results in improved recovery of heart contractility and reduced left ventricular end-diastolic pressure, in contrast to the effects of aspirin. The combination of improved analgesia, reduced gastrointestinal toxicity and cardiorenal protection has been established in animal models, and early clinical results suggest a favourable gastrointestinal safety profile in humans. The potential for CINODs to provide cardiorenal protection in humans is currently being investigated.
Muscará
Marcelo N
MN
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, São Paulo, 05508-900 SP, Brazil. muscara@usp.br
Wallace
John L
JL
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D009203:Myocardial Infarction / Q000188:drug therapy; D020030:Nitric Oxide Donors / Q000494:pharmacology* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D020030:Nitric Oxide Donors