Endothelial NOS‐independent release of nitric oxide in the aorta of the spontaneously hypertensive rat

Abstract

Preliminary experiments showed that in the aorta of male spontaneously hypertensive (SHR), but not in that of normotensive Wistar‐Kyoto (WKY) rats, contractions to phenylephrine (PE) are inhibited in preparations with endothelium despite the presence of indomethacin and L‐NAME. The present study aimed to identify the mechanism underlying this endothelium‐dependent inhibition in the SHR aorta. Aortic rings, with and without endothelium, of male SHR and WKY were suspended in organ chambers for the measurement of isometric tension. Contractions to PE were smaller in SHR aorta with than in those without endothelium. The inhibitory effect of the endothelium was larger in preparations from adult than in those from young SHR. The endothelium‐dependent difference in contraction to PE was abolished by the NO scavengers oxyhemoglobin and carboxy‐PTIO, by the inhibitor of soluble guanylyl cyclase ODQ, and the by inhibitor of cytochrome P450 reductase (CPR) diphenyleneiodonium. PE‐induced contractions in adult WKY aortic rings with endothelium were not affected by carboxy‐PTIO. Thus, in the SHR, there is an endothelium‐dependent release of NO which is not produced by NOS but by CPR. Nitrate is the likely source of this NOS‐independent endothelial NO. The NOS‐independent NO release is observed only in preparations from hypertensive animals and increases with age (supported by the Hong Kong Research Grant Council).