Journal article
Reduced blood pressure of CFTR-F508del carriers correlates with diminished arterial reactivity rather than circulating blood volume in mice
PloS one, Vol.9(5), pp.e96756-e96756
2014
DOI: 10.1371/journal.pone.0096756
PMCID: PMC4011854
PMID: 24801204
Abstract
The F508del mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) is the most common cause of cystic fibrosis (CF). Both CF patients and F508del carriers have decreased blood pressure. While this has been attributed to salt depletion, recent studies have shown F508del expression interferes with smooth muscle cell calcium mobilization. We tested the hypothesis that carriers of the F508del mutation have lower adult blood pressures and reduced aortic contractility without a reduction in circulating blood volume. By radiotelemetry, F508del heterozygous mice had significantly lower arterial pressures than wild-type C57BL/6 controls, with the greatest effect seen at the time of dark-to-light cycle transition (mean difference of 10 mmHg). To replicate the vascular effects of sympathetic arousal, isoproterenol and epinephrine were co-infused, and F508del mice again had significantly reduced arterial pressures. Aortas isolated from F508del heterozygous mice had significantly decreased constriction to noradrenaline (0.9 ± 0.2 versus 2.9 ± 0.7 mN). Inhibition of wild-type CFTR or the inositol triphosphate receptor replicated the phenotype of F508del aortas. CFTR carrier status did not alter circulating blood volume. We conclude the CFTR-F508del mutation decreases aortic contractility and lowers arterial pressures. As a cAMP-activated chloride channel that facilitates calcium mobilization, we speculate wild-type CFTR co-activation during adrenergic receptor stimulation buffers the vasodilatory response to catecholamines, and loss of this compensatory vasoconstrictor tone may contribute to the lower arterial pressures seen in heterozygote carriers of a CFTR-F508del mutation.
Details
- Title: Subtitle
- Reduced blood pressure of CFTR-F508del carriers correlates with diminished arterial reactivity rather than circulating blood volume in mice
- Creators
- Veronica A Peotta - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of AmericaPrasad Bhandary - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of AmericaUgochi Ogu - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of AmericaKenneth A Volk - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of AmericaRobert D Roghair - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.9(5), pp.e96756-e96756
- DOI
- 10.1371/journal.pone.0096756
- PMID
- 24801204
- PMCID
- PMC4011854
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science
- Grant note
- R01 HL102659 / NHLBI NIH HHS HL102659 / NHLBI NIH HHS
- Language
- English
- Date published
- 2014
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology; Internal Medicine
- Record Identifier
- 9984093211602771
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