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Defining the roles of arrestin2 and arrestin3 in vasoconstrictor receptor desensitization in hypertension.

Willets JM, Nash CA, Rainbow RD, Nelson CP, Challiss RA - Am. J. Physiol., Cell Physiol. (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, United Kingdom; and jmw23@leicester.ac.uk.

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Assessment of ET1 and UTP-stimulated PLC signaling desensitization in SHR and WKY MSMC from 12-wk-old animals. MSMC were transfected with eGFP-PH (0.5 μg) before being subjected to the following desensitization protocols: For ET1, MSMC were stimulated with ET1 (50 nM, 30 s; R1); with 5 min washout before a second challenge (50 nM, 30 s; R2), while for UTP, MSMC were challenged with a ∼EC50 UTP concentration (10 μM) for 30 s before (R1) and after (R2) addition of a maximal UTP concentration (Rmax: 100 μM, for 1 min). Representative traces are shown from single cells isolated from WKY (A and C) and SHR (B and D) treated with either ET1 (A and B) or UTP (C and D). Receptor desensitization was determined as the relative change in R2 response compared with R1. Cumulative data (E) are expressed as means ± SE for the % change in R2 relative to R1; n = 10–18 cells from ≥4 separate animals. Statistical significance is indicated as *P < 0.05; ***P < 0.001 vs. WKY (one-way ANOVA and Dunnett's post hoc test).
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Figure 6: Assessment of ET1 and UTP-stimulated PLC signaling desensitization in SHR and WKY MSMC from 12-wk-old animals. MSMC were transfected with eGFP-PH (0.5 μg) before being subjected to the following desensitization protocols: For ET1, MSMC were stimulated with ET1 (50 nM, 30 s; R1); with 5 min washout before a second challenge (50 nM, 30 s; R2), while for UTP, MSMC were challenged with a ∼EC50 UTP concentration (10 μM) for 30 s before (R1) and after (R2) addition of a maximal UTP concentration (Rmax: 100 μM, for 1 min). Representative traces are shown from single cells isolated from WKY (A and C) and SHR (B and D) treated with either ET1 (A and B) or UTP (C and D). Receptor desensitization was determined as the relative change in R2 response compared with R1. Cumulative data (E) are expressed as means ± SE for the % change in R2 relative to R1; n = 10–18 cells from ≥4 separate animals. Statistical significance is indicated as *P < 0.05; ***P < 0.001 vs. WKY (one-way ANOVA and Dunnett's post hoc test).

Mentions: The R2/R1 ratios obtained for ET1- and UTP-mediated desensitization in WKY MSMC (both at 6 and 12 wk; Figs. 5 and 6) were similar and were also comparable to those previously observed in adult Wistar MSMC (21, 22). Comparison of experiments undertaken in MSMC isolated from 6-wk-old animals showed that the extent of ET1- and UTP-induced receptor desensitization was comparable in SHR- and WKY-derived cells (Fig. 5E). When similar experiments were conducted in MSMC preparations from 12-wk-old animals, R2/R1 ratios were markedly decreased in SHR- compared with WKY-derived cells, indicating that a greater desensitization of ET1- and UTP-PLC signaling was observed in cells derived from 12-wk, but not 6-wk-old SHR (Fig. 6E).


Defining the roles of arrestin2 and arrestin3 in vasoconstrictor receptor desensitization in hypertension.

Willets JM, Nash CA, Rainbow RD, Nelson CP, Challiss RA - Am. J. Physiol., Cell Physiol. (2015)

Assessment of ET1 and UTP-stimulated PLC signaling desensitization in SHR and WKY MSMC from 12-wk-old animals. MSMC were transfected with eGFP-PH (0.5 μg) before being subjected to the following desensitization protocols: For ET1, MSMC were stimulated with ET1 (50 nM, 30 s; R1); with 5 min washout before a second challenge (50 nM, 30 s; R2), while for UTP, MSMC were challenged with a ∼EC50 UTP concentration (10 μM) for 30 s before (R1) and after (R2) addition of a maximal UTP concentration (Rmax: 100 μM, for 1 min). Representative traces are shown from single cells isolated from WKY (A and C) and SHR (B and D) treated with either ET1 (A and B) or UTP (C and D). Receptor desensitization was determined as the relative change in R2 response compared with R1. Cumulative data (E) are expressed as means ± SE for the % change in R2 relative to R1; n = 10–18 cells from ≥4 separate animals. Statistical significance is indicated as *P < 0.05; ***P < 0.001 vs. WKY (one-way ANOVA and Dunnett's post hoc test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525080&req=5

Figure 6: Assessment of ET1 and UTP-stimulated PLC signaling desensitization in SHR and WKY MSMC from 12-wk-old animals. MSMC were transfected with eGFP-PH (0.5 μg) before being subjected to the following desensitization protocols: For ET1, MSMC were stimulated with ET1 (50 nM, 30 s; R1); with 5 min washout before a second challenge (50 nM, 30 s; R2), while for UTP, MSMC were challenged with a ∼EC50 UTP concentration (10 μM) for 30 s before (R1) and after (R2) addition of a maximal UTP concentration (Rmax: 100 μM, for 1 min). Representative traces are shown from single cells isolated from WKY (A and C) and SHR (B and D) treated with either ET1 (A and B) or UTP (C and D). Receptor desensitization was determined as the relative change in R2 response compared with R1. Cumulative data (E) are expressed as means ± SE for the % change in R2 relative to R1; n = 10–18 cells from ≥4 separate animals. Statistical significance is indicated as *P < 0.05; ***P < 0.001 vs. WKY (one-way ANOVA and Dunnett's post hoc test).
Mentions: The R2/R1 ratios obtained for ET1- and UTP-mediated desensitization in WKY MSMC (both at 6 and 12 wk; Figs. 5 and 6) were similar and were also comparable to those previously observed in adult Wistar MSMC (21, 22). Comparison of experiments undertaken in MSMC isolated from 6-wk-old animals showed that the extent of ET1- and UTP-induced receptor desensitization was comparable in SHR- and WKY-derived cells (Fig. 5E). When similar experiments were conducted in MSMC preparations from 12-wk-old animals, R2/R1 ratios were markedly decreased in SHR- compared with WKY-derived cells, indicating that a greater desensitization of ET1- and UTP-PLC signaling was observed in cells derived from 12-wk, but not 6-wk-old SHR (Fig. 6E).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, United Kingdom; and jmw23@leicester.ac.uk.

Show MeSH
Related in: MedlinePlus