Defining the roles of arrestin2 and arrestin3 in vasoconstrictor receptor desensitization in hypertension.
Bottom Line: Desensitization of UTP-stimulated vessel contractions was increased in 12-wk-old (but not 6-wk-old) SHR animals.In conclusion, arrestin2 and 3 expression is elevated in resistance arteries during the emergence of the early hypertensive phenotype, which underlies an enhanced ability to desensitize vasoconstrictor signaling and vessel contraction.Such regulatory changes may act to compensate for increased vasoconstrictor-induced vessel contraction.
Affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, United Kingdom; and firstname.lastname@example.org.Show MeSH
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Mentions: Analysis of protein expression in the resistance arteries of the mesenteric tree of 6-wk-old animals showed there were no significant differences in arrestin expression in the vessels of SHR and WKY at this age (Fig. 1, A and B). Arrestin expression was also similar in aortae from 6-wk-old SHR and WKY animals (Fig. 1, C and D). At 12 wk of age, SHRs displayed significantly increased heart weight-to-body weight ratio compared with WKY rats (data not shown). In contrast to our findings in 6-wk-old animals, arrestin2 expression was significantly increased in both mesenteric vessels and aortae of 12-wk-old SHR compared with WKY rats (Fig. 1, A–D), with the highest expression being observed in SHR mesentery. Interestingly, arrestin3 expression was only significantly elevated in SHR mesentery (Fig. 1). No changes in arrestin2/3 expression were observed in other smooth muscle types (colon, bladder) or in the heart (Fig. 2), suggesting that the increases in arrestin isoform expression in arterial smooth muscle are tissue- and phenotype-specific changes. Importantly, the observed ex vivo differences in arrestin expression were preserved in mesenteric arterial smooth muscle cells (MSMC) isolated from 12-wk-old animals and maintained for 7 days under our culture conditions (Fig. 1, A and B).
Affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, United Kingdom; and email@example.com.