| Increased blood pressure and hyperdynamic cardiovascular responses in carriers of a common hyperfunctional variant of adenylyl cyclase 6. | |
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MedLine Citation:
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PMID: 20732959 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Adenylyl cyclase (ADCY) is a critical regulator of metabolic and cardiovascular function. We have identified a genetic variant (A674S) in ADCY isoform 6 (ADCY6). Subsequent studies demonstrated that the expression of this ADCY6 variant paralleled an increase in adenylyl cyclase-mediated functions. However, the impact of this hyperfunctional variant on cardiovascular function is unknown. Therefore, we evaluated the hemodynamic profile of carriers of ADCY6 A674S. The association of ADCY6 A674S with anthropometric and hemodynamic parameters was assessed in 364 healthy white subjects. The allele encoding this variant was present in 6.9% of the subjects, and those individuals had increased blood pressure. To determine the hemodynamic basis for increased blood pressure in carriers of ADCY6 A674S, we assessed forearm blood flow (FBF) and cardiac output at rest, during handgrip exercise (to test vasodilator responsiveness), and with lower body negative pressure [to test forearm vasoconstrictor and heart rate (HR) responsiveness] in a subsample of 21 subjects. At rest, cardiac output and blood pressure were higher in carriers of ADCY6 A674S. This was paralleled by an increase in plasma renin activity, but not in plasma norepinephrine. During handgrip exercise, FBF and vasodilator responses were greater in carriers of ADCY6 A674S. Responses to reactive hyperemia were not different between genotypes. With lower body negative pressure, the HR response to this orthostatic stress was markedly higher in carriers of ADCY6 A674S. These data indicate that the relatively common hyperfunctional ADCY6 A674S variant underlies a hyperdynamic cardiovascular response and increased blood pressure. |
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Authors:
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Gary J Hodges; Robert Gros; Robert A Hegele; Stan Van Uum; J Kevin Shoemaker; Ross D Feldman |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-23 |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 335 ISSN: 1521-0103 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-20 Completed Date: 2010-11-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
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Languages: eng Pagination: 451-7 Citation Subset: IM |
Affiliation:
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Robarts Research Institute, P.O. Box 5015, 100 Perth Drive, London, ON, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenylate Cyclase
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genetics* Adolescent Adult Anthropometry Blood Pressure / genetics* Cardiac Output / genetics Cardiovascular Physiological Phenomena / genetics* Exercise Forearm / blood supply Gene Frequency Genetic Variation* Genotype Heart Rate / genetics Humans Lower Body Negative Pressure Middle Aged Regional Blood Flow / genetics Vasoconstriction / genetics Vasodilation / genetics Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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EC 4.6.1.1/Adenylate Cyclase; EC 4.6.1.1/adenylyl cyclase 6 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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