Nitric oxide-releasing aspirin inhibits vasoconstriction in perfused tail artery of normotensive and spontaneously hypertensive rats.
The aim of this study was to investigate the capacity of the 2-(acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl ester (NCX 4016), a nitric oxide (NO)-releaser derivative of aspirin, to decrease blood pressure in spontaneously hypertensive rats (SHR) and to counteract the adrenergic vasoconstriction in perfused tail artery of these animals. Oral treatment for 10 consecutive days with NCX 4016 (100 micromol/kg) in SHR and their genetic controls Wistar Kyoto (WKY) rats resulted in a reduction of blood pressure in SHR but not in WKY rats. In SHR, the NCX 4016 treatment increased the serum nitrite/nitrate and diminished the serum thromboxane B2, whereas aspirin did not change blood pressure but abolished the serum thromboxane B2. Perfused tail arteries excised from vehicle-treated SHR exhibited a significant impairment of endothelium-dependent vasorelaxant function. These vessels, prepared from SHR or WKY rats treated orally with NCX 4016 (10, 30 and 100 micromol/kg for 7 consecutive days), revealed a dose-dependent decrease in vasoconstriction in response to transmural nerve stimulation and norepinephrine, whereas aspirin was ineffective. Furthermore, in tail arteries of both SHR and WKY rats treated orally with NCX 4016 (100 micromol/kg for 7 consecutive days), the cGMP increased significantly. In conclusion, NCX 4016, by releasing NO and increasing cGMP in vascular tissue, reduces sympathetic-mediated vasoconstriction in resistance vessels and lowers blood pressure in SHR.
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009566:Nitrates / Q000097:blood; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009573:Nitrites / Q000097:blood; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013623:Tail / Q000098:blood supply; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*
D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D013929:Thromboxane B2; C102148:nitroaspirin; D006152:Cyclic GMP; D001241:Aspirin