ABSTRACT
BACKGROUND: The use of non-steroidal anti-inflammatory drugs (NSAIDs) is frequently limited by adverse effects resulting from the disruption of homeostatic functions of prostaglandins. OBJECTIVES: This study was aimed at the evaluation of the effect of selective COX-2 inhibitor meloxicam on vasoconstrictor responses to noradrenaline (NA) in rabbit renal artery chosen as a model vessel and in rabbit ear artery as a peripheral artery under in vitro conditions. METHODS: Rabbit renal and ear arteries were perfused at constant flow. Vascular responses to NA before and after meloxicam administration and after deendothelisation by air bubbles were measured and registered as changes in perfusion pressure. RESULTS: It was found out that vasoconstrictor responses to noradrenaline when exposed to meloxicam were not enhanced significantly in both arterial preparations. Deendothelisation itself did not increase responses affected by meloxicam in the renal and ear arteries but in comparison with control groups the responses were significantly augmented, especially in the ear artery. CONCLUSIONS: The results obtained in this study demonstrate that meloxicam had not affected adversely the vasoconstrictor activity in different types of vessels without selectivity on vascular beds. Endothelial removal potentiated vasoconstrictor responses in arteries pre-treated by meloxicam when compared with intact vessels. (Tab. 2, Fig. 4, Ref. 19.)
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Ear, External/blood supply , Endothelium, Vascular/physiology , Renal Artery/physiology , Thiazines/pharmacology , Thiazoles/pharmacology , Vasoconstriction/drug effects , Animals , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , In Vitro Techniques , Isoenzymes/antagonists & inhibitors , Meloxicam , Norepinephrine/pharmacology , Prostaglandin-Endoperoxide Synthases , Rabbits , Renal Artery/drug effects , Vasoconstrictor Agents/pharmacologyABSTRACT
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to induce adverse renal effects, which are closely related to physiological inhibition of renal prostaglandin synthesis. AIM: This study was aimed to evaluate the effect of drugs inhibiting both cyclooxygenase (COX) isoforms COX-1 and COX-2 on vasoconstrictor responses to noradrenaline in the rabbit renal artery and to compare these responses with femoral artery as a systemic vessel. METHODS: Rabbit femoral and renal arteries were perfused with a constant flow. Vascular responses to drugs were measured and registered as changes in perfusion pressure. RESULTS: It was found that the vasoconstrictor responses to noradrenaline were significantly enhanced after administration of all NSAIDs in both the renal and femoral arteries. The effect of indomethacin on renal vasoconstrictor responses was more pronounced compared to ibuprofen or phenacetin. Comparison of NSAIDs effects on renal and femoral arteries did not show significant differences. CONCLUSIONS: These results demonstrate an increase of vasoconstrictor activity after NSAIDs administration without significant differences between the renal and femoral arteries. The strongest potentiation of the vasoconstrictor responses in the renal artery was found with indomethacin. (Tab. 1, Fig. 4, Ref. 20.)
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Femoral Artery/drug effects , Renal Artery/drug effects , Vasoconstriction/drug effects , Animals , Cyclooxygenase Inhibitors/pharmacology , Femoral Artery/physiology , Ibuprofen/pharmacology , In Vitro Techniques , Indomethacin/pharmacology , Phenacetin/pharmacology , Rabbits , Renal Artery/physiologyABSTRACT
Non-opioid analgesics are some of the most widely used therapeutic agents in clinical practice today. The number of patients at risk for adverse events related to the use of these agents is rapidly expanding. While the gastrointestinal toxicity of these medications is well known, it has become increasingly apparent that the kidney is also an important target for untoward clinical events. Evidence of the nephrotoxicity of analgesic preparations is not sufficiently completed and available in our region. Analgesic-related renal injury has been classified based on mechanism of action into "classic" analgesic nephropathy and NSAID-related renal toxicity. From clinical point of view the renal side effects induced by analgesics can be classified into hemodynamic (functional) side effects and idiosyncratic side effects. The common link in both types of side effects seems to be renal ischemia related to prostaglandin synthesis inhibition. Key enzyme in this process is cyclooxygenase occurring in two isoforms: COX-1 and COX-2. Antiinflammatory effect of NSAIDs is mediated by COX-2 inhibition, while the side effects (gastrotoxicity, nephrotoxicity) by inhibition of COX-1. COX-1 was more inhibited by indomethacin and piroxicam and COX-2 by 6-MNA (active metabolite of nabumetone), diclofenac and ibuprofen. Nimesulide and meloxicam selectively block COX-2 and are recommended to patients at risk or treated with diuretics. (Tab. 2, Fig. 2, Ref. 38.)
