Vasorelaxant effect of nitric oxide releasing steroidal and nonsteroidal anti‐inflammatory drugs

• Published in: British journal of pharmacology Vol. 133; no. 7; pp. 1023 - 1028
• Main Authors: Keeble, J, Al‐Swayeh, O A, Moore, P K
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2001; Nature Publishing
• Subjects: Acetaminophen - analogs & derivatives; Acetaminophen - pharmacology; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; aorta; Aorta - drug effects; Aorta - physiology; Aspirin - analogs & derivatives; Aspirin - pharmacology; Biological and medical sciences; Blood Pressure - drug effects; Bones, joints and connective tissue. Antiinflammatory agents; Dose-Response Relationship, Drug; Flurbiprofen - analogs & derivatives; Flurbiprofen - pharmacology; In Vitro Techniques; kidney; Kidney - drug effects; Kidney - physiology; Male; Medical sciences; mesentery; Mesentery - drug effects; Mesentery - physiology; Nitric Oxide - metabolism; nitroaspirin; nitroflurbiprofen; nitroparacetamol; nitroprednisolone; Nitroprusside - pharmacology; NO‐NSAID; Pharmacology. Drug treatments; Prednisolone - analogs & derivatives; Prednisolone - pharmacology; Rats; Rats, Wistar; Vasodilation - drug effects; Vasodilator Agents - pharmacology; Corticosteroid; Intraperitoneal administration; Vasodilator agent; Rat; Rodentia; Antiinflammatory agent; Smooth muscle; In vitro; Biological activity; Non steroidal antiinflammatory agent; Muscular relaxation; In vivo; Vertebrata; Mammalia; Animal; Nitric oxide; Blood vessel; Circulatory system; Comparative study
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0704161

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; EC50, 688.8±93.8 μM), nitroaspirin (NOA; EC50, 57.9±6.5 μM), nitroparacetamol (NOPARA; EC50, 71.5±14.6 μM) and nitroprednisolone (EC50, 15.1±1.4 μM) 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, EC50, 35.7±3.5 nM). The vasorelaxant effect of NOF and NOPARA in the rat aorta was potentiated by zaprinast (5 μM) and reduced by ODQ (5 μM). Flurbiprofen and paracetamol (100 μM) 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 μM; EC30, 181.8±35.1 μM cf. EC30, 125.1±17.0 μM, P>0.05) but increased by removal of the endothelium (EC30, 164.3±26.3 μM cf. EC50, 688.8±93.8 μM, P<0.05). NOF (0.1–50 μM) produced a small but not concentration‐related vasodilation of the NA‐preconstricted (i.e. ‘high tone’) perfused rat mesentery preparation (cf. SNP, EC30, 4.4±0.7 μM). In contrast, NOF (1–100 μM) produced concentration‐related vasodilation of the ‘high tone’ perfused rat kidney with an EC50 of 33.1±4.4 μM. 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