title: Elevated systolic blood pressure in male GH transgenic mice is age dependent.
abstract: Acromegaly is associated with an increased incidence of cardiovascular disease. Transgenic mice expressing bovine GH (bGH) gene have previously been used to examine the effects of chronic GH stimulation on cardiovascular function. Results concerning systolic blood pressure (SBP) in bGH mice are conflicting. We hypothesized that these discrepancies may be the result of the various ages of the mice used in previous studies. In the current study, SBP was assessed monthly in male bGH mice from 3-12 months of age. Factors known to alter blood pressure were assessed during this time and included: levels of brain natriuretic peptide (BNP) and glucose homeostasis markers, and renal levels of angiotensin-converting enzyme 2 and endothelial nitric oxide synthase. Beginning at 6 months of age bGH had increased SBP compared with wild-type controls, which remained elevated through 12 months of age. Despite having increased blood pressure and cardiac BNP mRNA, bGH mice had decreased circulating levels of BNP. Additionally, bGH mice had an age-dependent decline in insulin levels. For example, they were hyperinsulinemic at 3 months, but by 11 months of age were hypoinsulinemic relative to wild-type controls. This decrease in insulin was accompanied by improved glucose tolerance at 11 months. Finally, both angiotensin-converting enzyme 2 and endothelial nitric oxide synthase expression were severely depressed in kidneys of 11-month-old bGH mice. These results indicate that elevated SBP in bGH mice is dependent on age, independent of insulin resistance, and related to alterations in both the natriuretic peptide and renin-angiotensin systems.
authors.affiliation: Edison Biotechnology Institute (A.J., C.M.B., D.S., X.L., E.O.L., L.A.H., D.E.B., J.J.K.) Ohio University, Athens, Ohio 45701; Department of Biomedical Sciences (A.J., D.E.B., J.J.K.) and Department of Specialty Medicine (E.O.L.), Heritage College of Osteopathic Medicine, Athens, Ohio 45701; School of Applied Health Sciences and Wellness (C.M.B., X.L., D.E.B.) College of Health Sciences and Professions, Ohio University, Athens, Ohio 45701; and Department of Biological Sciences (A.J., J.J.K.) and Department of Social and Public Health (D.S.), Ohio University, Athens, Ohio 45701.
authors.forename: Adam
authors.initials: A
authors.lastname: Jara
authors.forename: Chance M
authors.initials: CM
authors.lastname: Benner
authors.forename: Don
authors.initials: D
authors.lastname: Sim
authors.forename: Xingbo
authors.initials: X
authors.lastname: Liu
authors.forename: Edward O
authors.initials: EO
authors.lastname: List
authors.forename: Lara A
authors.initials: LA
authors.lastname: Householder
authors.forename: Darlene E
authors.initials: DE
authors.lastname: Berryman
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
mesh_terms: D000172:Acromegaly / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001794:Blood Pressure; D001823:Body Composition; D001835:Body Weight; D002417:Cattle; D004195:Disease Models, Animal; D005355:Fibrosis / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000097:blood* / Q000235:genetics*; D006706:Homeostasis; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012084:Renin-Angiotensin System; D013599:Systole; D013997:Time Factors
chemical_list: D007328:Insulin; D020097:Natriuretic Peptide, Brain; D013006:Growth Hormone; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; D005947:Glucose