Vasorelaxant effects of a nitric oxide-releasing aspirin derivative in normotensive and hypertensive rats

1 Nonsteroidal anti-inflammatory drugs have been reported to exacerbate hyp ertension and to interfere with the effectiveness of some anti-hypertensive therapies. In this study, we tested the effects of a gastric-sparing, nitr ic oxide-releasing derivative of aspirin (NCX-4016) on hypertension in rats . 2 Hypertension was induced by administering L-NAME in the drinking water (4 00 mg l(-1)). Groups of rats were treated daily with aspirin, NCX-4016 or v ehicle. 3 NCX-4016 significantly reduced blood pressure relative to the aspirin-tre ated group over the 2-week period of treatment. Aspirin and, to a lesser ex tent, NCX-4016 suppressed whole blood thromboxane synthesis. 4 In anaesthetized rats. acute intravenous administration of NCX-4016 cause d a significant fall in mean arterial pressure in hypertensive rats, but wa s devoid of such effects in normotensive controls. 5 In vitro. NCX-4016 relaxed phenylephrine-pre-contracted aortic rings obta ined from both normotensive and hypertensive rats, and significantly reduce d their responsiveness to the contractile effects of phenylephrine. 6 These results suggest that NCX-4016 reduces blood pressure in hypertensiv e rats, not simply through the direct vasodilatory actions of the nitric ox ide released by this compound, but also through possible interference with the effects of endogenous pressor agents. These properties. added to its an ti-thrombotic effects, suggest that NCX-4016 may be a safer alternative to aspirin for use by hypertensive patients.