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Vasorelaxant effect of nitric oxide releasing steroidal and nonsteroidal anti‐inflammatory drugs
Author(s) -
Keeble J,
AlSwayeh O A,
Moore P K
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704161
Subject(s) - sodium nitroprusside , nitric oxide , zaprinast , chemistry , vasodilation , pharmacology , in vivo , medicine , endocrinology , biology , cyclic gmp , microbiology and biotechnology , organic chemistry
The effect of several nitric oxide releasing‐non‐steroidal anti‐inflammatory drugs (NO‐NSAID) and nitroprednisolone on blood vessel relaxation in vitro and in vivo was studied. Nitroflurbiprofen (NOF; EC 50 , 688.8±93.8 μ M ), nitroaspirin (NOA; EC 50 , 57.9±6.5 μ M ), nitroparacetamol (NOPARA; EC 50 , 71.5±14.6 μ M ) and nitroprednisolone (EC 50 , 15.1±1.4 μ M ) caused concentration‐related relaxation of noradrenaline (NA)‐contracted rat aortic rings. All NO releasing compounds tested were approximately three orders of magnitude less potent than sodium nitroprusside (SNP, EC 50 , 35.7±3.5 n M ). The vasorelaxant effect of NOF and NOPARA in the rat aorta was potentiated by zaprinast (5 μ M ) and reduced by ODQ (5 μ M ). Flurbiprofen and paracetamol (100 μ M ) caused minimal (<10%) relaxation of the rat aorta and did not affect the response to SNP. The effect of NOF was unchanged in the presence of L ‐NAME (100 μ M ; EC 30 , 181.8±35.1 μ M cf. EC 30 , 125.1±17.0 μ M , P >0.05) but increased by removal of the endothelium (EC 30 , 164.3±26.3 μ M cf. EC 50 , 688.8±93.8 μ M , P <0.05). NOF (0.1–50 μ M ) produced a small but not concentration‐related vasodilation of the NA‐preconstricted (i.e. ‘high tone’) perfused rat mesentery preparation (cf. SNP, EC 30 , 4.4±0.7 μ M ). In contrast, NOF (1–100 μ M ) produced concentration‐related vasodilation of the ‘high tone’ perfused rat kidney with an EC 50 of 33.1±4.4 μ M . Neither NOF (74 mg kg −1 , i.p.) nor NOA (91.9 mg kg −1 , i.p.) nor equimolar doses of flurbiprofen (50 mg kg −1 , i.p.) or aspirin (50 mg kg −1 , i.p.) affected mean arterial blood pressure (MAP) or heart rate (HR) of pentobarbitone‐anaesthetized rats over a 1 h period. NO‐NSAID relax blood vessels in vitro by an NO‐dependent mechanism. The absolute vasorelaxant effect of NO releasing drug varies greatly with the choice of compound and between blood vessel preparations.British Journal of Pharmacology (2001) 133 , 1023–1028; doi: 10.1038/sj.bjp.0704161