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 email@example.com.Show MeSH
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Mentions: The ability of repeated UTP additions to diminish subsequent vessel contractions was compared in SHR- versus WKY-derived mesenteric arteries as an index of intact vessel “desensitization.” Artery rings were challenged with an approximate EC50 concentration of UTP, for 5 min before (R1) and after (R2) addition of a maximal UTP concentration for 5 min (Rmax). Arteries were washed for 5 min between R1 and Rmax, and Rmax and R2 agonist challenges. The R2/R1 ratio is interpreted as an index of receptor desensitization (21, 22). Since the relative potency of UTP was different between rat strains, we applied an EC50 (R1 and R2) concentration of either 100 μM or 200 μM, and Rmax concentration of 300 μM or 500 μM UTP for SHR and WKY vessels, respectively. In all cases, R2 responses were reduced compared with R1 after stimulation with a maximal agonist concentration (Fig. 4, A–D) and the reductions in R2/R1 ratio seen with WKY vessels (at both ages) were similar to that previously observed in vessels obtained from male adult Wistar animals (21). R2/R1 ratios were similar in vessels from 6-wk-old SHR and WKY rats (Fig. 4, A, B, and E); however, in vessels from 12-wk-old SHR the R2 response was further suppressed compared with age-matched WKY (decrease in R2 relative to R1: 64.3 ± 5.9% for SHR compared with 32.3 ± 11.3% for WKY; P < 0.05), indicating a significantly greater desensitization of UTP-stimulated SHR vessel contractions (Fig. 4E).
Affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, United Kingdom; and firstname.lastname@example.org.