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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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Related in: MedlinePlus

Comparison of contractile responses in mesenteric arteries from pre- and posthypertensive SHR and normotensive WKY rats. A: cumulative data showing third-order mesenteric arterial ring contraction (means ± SE) to K+ (60 mM) and endothelin-1 (ET1; 3 nM) for n ≥ 5 arterial preparations from at least 5 separate 6-wk-old SHR and WKY animals for each treatment. Statistical significance is indicated as *P < 0.05 SHR vs. WKY (unpaired t-test). B: concentration-dependency of UTP-stimulated contractions in SHR and WKY arteries from 6-wk-old animals (data are means ± SE for n ≥ 5 arterial preparations from at least 8 separate animals for each treatment). C: cumulative data showing the relative contractions of mesenteric arteries from 6-wk-old SHR and WKY animals (data are means ± SE for n = 7–19 arterial preparations from at least 7 separate animals for each treatment). Statistical significance is indicated as *P < 0.05 SHR vs. WKY (unpaired t-test). D: concentration-dependency of UTP-stimulated contractions in SHR and WKY arteries from 12-wk-old animals (data are means ± SE for n = 8 arterial preparations from at least 8 separate animals for each treatment). Statistical significance is indicated as *P < 0.05; **P < 0.01, SHR vs. WKY (two-way ANOVA and Bonferroni's post hoc test). E: concentration-dependency of UTP-stimulated Ca2+ signaling in MSMC prepared from 12-wk-old SHR and WKY animals. Data are means ± SE for n = 98–275 cells from at least 5 separate preparations for each animal strain. Statistical significance is indicated as **P < 0.01; ***P < 0.001, SHR vs. WKY (one-way ANOVA and Dunnett's post hoc test).
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Figure 3: Comparison of contractile responses in mesenteric arteries from pre- and posthypertensive SHR and normotensive WKY rats. A: cumulative data showing third-order mesenteric arterial ring contraction (means ± SE) to K+ (60 mM) and endothelin-1 (ET1; 3 nM) for n ≥ 5 arterial preparations from at least 5 separate 6-wk-old SHR and WKY animals for each treatment. Statistical significance is indicated as *P < 0.05 SHR vs. WKY (unpaired t-test). B: concentration-dependency of UTP-stimulated contractions in SHR and WKY arteries from 6-wk-old animals (data are means ± SE for n ≥ 5 arterial preparations from at least 8 separate animals for each treatment). C: cumulative data showing the relative contractions of mesenteric arteries from 6-wk-old SHR and WKY animals (data are means ± SE for n = 7–19 arterial preparations from at least 7 separate animals for each treatment). Statistical significance is indicated as *P < 0.05 SHR vs. WKY (unpaired t-test). D: concentration-dependency of UTP-stimulated contractions in SHR and WKY arteries from 12-wk-old animals (data are means ± SE for n = 8 arterial preparations from at least 8 separate animals for each treatment). Statistical significance is indicated as *P < 0.05; **P < 0.01, SHR vs. WKY (two-way ANOVA and Bonferroni's post hoc test). E: concentration-dependency of UTP-stimulated Ca2+ signaling in MSMC prepared from 12-wk-old SHR and WKY animals. Data are means ± SE for n = 98–275 cells from at least 5 separate preparations for each animal strain. Statistical significance is indicated as **P < 0.01; ***P < 0.001, SHR vs. WKY (one-way ANOVA and Dunnett's post hoc test).

Mentions: Since expression of arrestin2 and arrestin3 was elevated in small mesenteric arteries of 12-wk-old SHR and considering their key roles in suppressing the signaling of several contractile GPCRs within the vasculature (4, 14, 21, 22), we next compared the abilities of vasoactive agents to induce vasoconstriction in both SHR and WKY arteries. When normalized to vessel tension, contractions induced by K+ (60 mM) were similar in WKY to our previous findings in arterial preparations of adult male Wistar rats (21). However, K+-induced contractions were greater in SHR- compared with WKY-derived mesenteric vessels irrespective of age (Fig. 3, A and C). In both WKY- and SHR-derived vessels, contractions induced by K+ were completely ablated by preaddition of the L-type voltage-operated Ca2+-channel antagonist, nifedipine (data not shown).


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)

Comparison of contractile responses in mesenteric arteries from pre- and posthypertensive SHR and normotensive WKY rats. A: cumulative data showing third-order mesenteric arterial ring contraction (means ± SE) to K+ (60 mM) and endothelin-1 (ET1; 3 nM) for n ≥ 5 arterial preparations from at least 5 separate 6-wk-old SHR and WKY animals for each treatment. Statistical significance is indicated as *P < 0.05 SHR vs. WKY (unpaired t-test). B: concentration-dependency of UTP-stimulated contractions in SHR and WKY arteries from 6-wk-old animals (data are means ± SE for n ≥ 5 arterial preparations from at least 8 separate animals for each treatment). C: cumulative data showing the relative contractions of mesenteric arteries from 6-wk-old SHR and WKY animals (data are means ± SE for n = 7–19 arterial preparations from at least 7 separate animals for each treatment). Statistical significance is indicated as *P < 0.05 SHR vs. WKY (unpaired t-test). D: concentration-dependency of UTP-stimulated contractions in SHR and WKY arteries from 12-wk-old animals (data are means ± SE for n = 8 arterial preparations from at least 8 separate animals for each treatment). Statistical significance is indicated as *P < 0.05; **P < 0.01, SHR vs. WKY (two-way ANOVA and Bonferroni's post hoc test). E: concentration-dependency of UTP-stimulated Ca2+ signaling in MSMC prepared from 12-wk-old SHR and WKY animals. Data are means ± SE for n = 98–275 cells from at least 5 separate preparations for each animal strain. Statistical significance is indicated as **P < 0.01; ***P < 0.001, SHR 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 3: Comparison of contractile responses in mesenteric arteries from pre- and posthypertensive SHR and normotensive WKY rats. A: cumulative data showing third-order mesenteric arterial ring contraction (means ± SE) to K+ (60 mM) and endothelin-1 (ET1; 3 nM) for n ≥ 5 arterial preparations from at least 5 separate 6-wk-old SHR and WKY animals for each treatment. Statistical significance is indicated as *P < 0.05 SHR vs. WKY (unpaired t-test). B: concentration-dependency of UTP-stimulated contractions in SHR and WKY arteries from 6-wk-old animals (data are means ± SE for n ≥ 5 arterial preparations from at least 8 separate animals for each treatment). C: cumulative data showing the relative contractions of mesenteric arteries from 6-wk-old SHR and WKY animals (data are means ± SE for n = 7–19 arterial preparations from at least 7 separate animals for each treatment). Statistical significance is indicated as *P < 0.05 SHR vs. WKY (unpaired t-test). D: concentration-dependency of UTP-stimulated contractions in SHR and WKY arteries from 12-wk-old animals (data are means ± SE for n = 8 arterial preparations from at least 8 separate animals for each treatment). Statistical significance is indicated as *P < 0.05; **P < 0.01, SHR vs. WKY (two-way ANOVA and Bonferroni's post hoc test). E: concentration-dependency of UTP-stimulated Ca2+ signaling in MSMC prepared from 12-wk-old SHR and WKY animals. Data are means ± SE for n = 98–275 cells from at least 5 separate preparations for each animal strain. Statistical significance is indicated as **P < 0.01; ***P < 0.001, SHR vs. WKY (one-way ANOVA and Dunnett's post hoc test).
Mentions: Since expression of arrestin2 and arrestin3 was elevated in small mesenteric arteries of 12-wk-old SHR and considering their key roles in suppressing the signaling of several contractile GPCRs within the vasculature (4, 14, 21, 22), we next compared the abilities of vasoactive agents to induce vasoconstriction in both SHR and WKY arteries. When normalized to vessel tension, contractions induced by K+ (60 mM) were similar in WKY to our previous findings in arterial preparations of adult male Wistar rats (21). However, K+-induced contractions were greater in SHR- compared with WKY-derived mesenteric vessels irrespective of age (Fig. 3, A and C). In both WKY- and SHR-derived vessels, contractions induced by K+ were completely ablated by preaddition of the L-type voltage-operated Ca2+-channel antagonist, nifedipine (data not shown).

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