Carvedilol increases blood pressure response to phenylephrine infusion in heart failure subjects with systolic dysfunction : evidence of improved vascular alpha1-adrenoreceptor signal transduction
INTRODUCTION: Alpha(1)-adrenergic receptor (alpha(1)-AR) stimulation produces smooth muscle contraction, vasoconstriction, and myocyte hypertrophy, suggesting a potential therapeutic role for alpha(1)-AR antagonists to reduce cardiac workload and myocardial hypertrophy. Preliminary reports suggest that vascular alpha(1)-ARs are desensitized in heart failure (HF) in a manner similar to myocardial beta(1)-ARs. We examined alpha(1)-AR signal transduction by repeat phenylephrine (PE) infusions in patients with HF receiving chronic carvedilol therapy.
METHODS: Twelve subjects with HF not currently receiving beta-blockers were up-titrated to maximum tolerable doses of carvedilol. Subjects underwent alpha(1)-AR stimulation testing at study baseline, 2 weeks after each dose titration, and 6 months after maintenance of maximum carvedilol dose. Phenylephrine infusions began at 0.5 microg kg(-1) min(-1), with dose titrations every 10 minutes, to a maximum of 5 microg kg(-1) min(-1). Phenylephrine dose response was evaluated by the PE rate required to elicit a 20 mm Hg increase in systolic blood pressure (BP), designated PS(20).
RESULTS: All doses of carvedilol significantly reduced preinfusion measures of heart rate, systolic BP, diastolic BP, and mean arterial pressure. However, carvedilol also produced a paradoxical trend toward PS(20) reduction (indicating increased PE response) that reached significance at the completion of carvedilol dose titration (PS(20) ratio vs baseline = 0.78; P < .001). All effects were maintained over a 6-month treatment period with no evidence of tolerance.
CONCLUSIONS: Increasing BP response to PE infusion suggests improvement in vascular alpha(1)-AR signal transduction with chronic carvedilol therapy. This effect is evident despite no detectable tolerance to preinfusion BP reductions. The varying affinities of alpha(1)-AR subtypes for carvedilol and PE may have contributed to this finding.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2008 |
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| Erschienen: |
2008 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:156 |
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| Enthalten in: |
American heart journal - 156(2008), 2 vom: 01. Aug., Seite 315-21 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Van Tassell, Benjamin W [VerfasserIn] |
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| Links: |
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| Themen: |
0K47UL67F2 |
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| Anmerkungen: |
Date Completed 05.08.2008 Date Revised 20.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ahj.2008.04.004 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM18119192X |
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| 100 | 1 | |a Van Tassell, Benjamin W |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Carvedilol increases blood pressure response to phenylephrine infusion in heart failure subjects with systolic dysfunction |b evidence of improved vascular alpha1-adrenoreceptor signal transduction |
| 264 | 1 | |c 2008 | |
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| 500 | |a Date Completed 05.08.2008 | ||
| 500 | |a Date Revised 20.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a INTRODUCTION: Alpha(1)-adrenergic receptor (alpha(1)-AR) stimulation produces smooth muscle contraction, vasoconstriction, and myocyte hypertrophy, suggesting a potential therapeutic role for alpha(1)-AR antagonists to reduce cardiac workload and myocardial hypertrophy. Preliminary reports suggest that vascular alpha(1)-ARs are desensitized in heart failure (HF) in a manner similar to myocardial beta(1)-ARs. We examined alpha(1)-AR signal transduction by repeat phenylephrine (PE) infusions in patients with HF receiving chronic carvedilol therapy | ||
| 520 | |a METHODS: Twelve subjects with HF not currently receiving beta-blockers were up-titrated to maximum tolerable doses of carvedilol. Subjects underwent alpha(1)-AR stimulation testing at study baseline, 2 weeks after each dose titration, and 6 months after maintenance of maximum carvedilol dose. Phenylephrine infusions began at 0.5 microg kg(-1) min(-1), with dose titrations every 10 minutes, to a maximum of 5 microg kg(-1) min(-1). Phenylephrine dose response was evaluated by the PE rate required to elicit a 20 mm Hg increase in systolic blood pressure (BP), designated PS(20) | ||
| 520 | |a RESULTS: All doses of carvedilol significantly reduced preinfusion measures of heart rate, systolic BP, diastolic BP, and mean arterial pressure. However, carvedilol also produced a paradoxical trend toward PS(20) reduction (indicating increased PE response) that reached significance at the completion of carvedilol dose titration (PS(20) ratio vs baseline = 0.78; P < .001). All effects were maintained over a 6-month treatment period with no evidence of tolerance | ||
| 520 | |a CONCLUSIONS: Increasing BP response to PE infusion suggests improvement in vascular alpha(1)-AR signal transduction with chronic carvedilol therapy. This effect is evident despite no detectable tolerance to preinfusion BP reductions. The varying affinities of alpha(1)-AR subtypes for carvedilol and PE may have contributed to this finding | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Adrenergic Antagonists |2 NLM | |
| 650 | 7 | |a Adrenergic alpha-Agonists |2 NLM | |
| 650 | 7 | |a Carbazoles |2 NLM | |
| 650 | 7 | |a Propanolamines |2 NLM | |
| 650 | 7 | |a Receptors, Adrenergic, alpha-1 |2 NLM | |
| 650 | 7 | |a Carvedilol |2 NLM | |
| 650 | 7 | |a 0K47UL67F2 |2 NLM | |
| 650 | 7 | |a Phenylephrine |2 NLM | |
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| 700 | 1 | |a Rondina, Matthew T |e verfasserin |4 aut | |
| 700 | 1 | |a Huggins, Franklin |e verfasserin |4 aut | |
| 700 | 1 | |a Gilbert, Edward M |e verfasserin |4 aut | |
| 700 | 1 | |a Munger, Mark A |e verfasserin |4 aut | |
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