TARGETING HEME OXIDISED NITRIC OXIDE-SENSITIVE GUANYLATE CYCLASE (NOGC) FOR SELECTIVE VASODILATION OF DISEASED BLOOD VESSELS

摘要

Background: An impaired function of the berne-containing NO receptor, NOGC, is often observed in disease states, possibly due to its oxidation and subsequent loss of the heme moiety. Interestingly, The NO-independent NOGC activator, BAY 58-2667, has been found to preferentially activate NOGC in its oxidised (Fe~(3+)) andheme-free states.Aim: This project aimed to determine if the redox state of NOGC alters in hypertension and if BAY 58-2667 is a more effective vasodilator of diseased versus non-diseased vessels. Methods: Thoracic aortae (-5 mm length) from normotensive (WKY) and spontaneously hypertensive rats (SHR) were mounted in organ baths and isometric force measured. Vessels were precontracted (~50%) with, cirazoline and cumulative concentration-response curves to NOGC activators which target NOGC in the Fe~(2+) (ACh, GTN, BAY 41-2272), Fe~(3+) (Angeli's salt, BAY 58-2667) and heme-free (BAY 58-2667) state were examined.