Abstract
In the aorta of male spontaneously hypertensive rats (SHR), but not in that of normotensive Wistar-Kyoto rats (WKY), contractions to phenylephrine obtained in the presence of L-NAME [inhibitor of nitric oxide synthase (NOS)] and indomethacin (inhibitor of cyclooxygenase) are inhibited by an unknown endothelium-derived factor. The present study aimed to identify the mechanism underlying this endothelium-dependent inhibition in the SHR aorta. Aortic rings of male SHR and WKY, with and without endothelium, were suspended in organ chambers in the presence of indomethacin and L-NAME for the measurement of isometric tension. Contractions to phenylephrine were smaller in SHR aortae with endothelium than in those without, but were similar in the two types of preparations of WKY aortae. The endothelium-dependent, NOS-independent inhibition of phenylephrine-induced contraction was abolished by oxyhemoglobin [extracellular NO scavenger], carboxy-PTIO (NO scavenger) and ODQ (inhibitor of soluble guanylyl cyclase). It was unmasked not only by indomethacin but also by apocynin (antioxidant), but inhibited by diphenyleneiodonium (inhibitor of flavoproteins including cytochrome P450 reductase). The cytochrome P450 reductase protein expression was similar in SHR and WKY aortae. However, the level of nitrate and nitrite, substrates of cytochrome P450 reductase, were higher in SHR than WKY plasma and aortae. Therefore, in SHR but not WKY aortae, eNOS-independent NO is formed by cytochrome P450 reductase.
Footnotes
The authors current research is supported by the Hong Kong Research Grant Council (University of Hong Kong, NO.769808M); Research Centre of Heart, Brain, Hormone & Healthy Aging of the University of Hong Kong; and the World Class University program (R31-20029) funded by the Ministry of Education, Science and Technology, South Korea.
Part of this work was presented previously as a poster: Zhao Y, Vanhoutte PM and Leung SWS (2012) Endothelial NOS-independent release of nitric oxide in the aorta of the spontaneously hypertensive rat, at the Experimental Biology 2012 Conference; 2012 April 21–25; San Diego, CA.
- Received July 25, 2012.
- Accepted August 30, 2012.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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