Key result
Hypertensive rats exhibit reduced dihydrobiopterin reductase and disrupted BH4 biosynthesis enzymes in aortic smooth muscle.
Why the study?
New targets for hypertension were sought by analyzing protein expression profiles in aortic smooth muscle of spontaneously hypertensive rats compared with normotensive controls.
Diminished expression of dihydropteridine reductase and subsequent BH4 deficiency may play a key role in vascular disorders associated with hypertension.
May implicate BH4 deficiency in hypertensive vascular dysfunction; leaves open therapeutic targeting in humans.
To identify the new targets for hypertension, we analyzed the protein expression profiles of aortic smooth muscle in spontaneously hypertensive rats (SHR) of various ages during the development of hypertension, as well as in age-matched normotensive Wistar-Kyoto (WKY) rats, using a proteomic analysis. The expressions of seven proteins were altered in SHR compared with WKY rats. Of these proteins, NADH dehydrogenase 1alpha, GSTomega1, peroxi-redoxin I and transgelin were upregulated in SHR compared with WKY rats. On the other hand, the expression of HSP27 and Ran protein decreased in SHR. The diminution of dihydrobiopterin reductase, an enzyme located in the regeneration pathways of tetrahydrobiopterin (BH4), was also prominent in SHR. The results from a PCR analysis revealed that the expression of BH4 biosynthesis enzymes - GTP cyclohydrolase-1 and sepiapterin reductase - decreased and increased, respectively, in SHR compared with WKY rats. The level of BH4 was less in aortic strips from SHR than from WKY rats. Moreover, treatment with BH4 inhibited aortic smooth muscle contraction induced by serotonin. These results suggest that the deficiency in BH4 regeneration produced by diminished dihydrobiopterin reductase expression is involved in vascular disorders in hypertensive rats.
No takes yet. Share an insight, caveat, or question.
Lee et al. (2009) studied Hypertension. Spontaneous hypertension vs. Normotensive Wistar-Kyoto (WKY) rats was evaluated on Protein expression profiles of aortic smooth muscle. Spontaneously hypertensive rats exhibited diminished expression of dihydrobiopterin reductase and altered BH4 biosynthesis enzymes compared to normotensive rats.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: