Effects of ovariectomy and growth hormone administration on body composition and vascular function and structure in old female rats.
ABSTRACT Aging and estrogen-deprivation induce deleterious effects on body composition and vascular function in females. On the other hand, growth hormone (GH), whose production is reduced by age, exerts several vascular effects. The aim of this study was to investigate the effect of long-term estrogen deprivation and GH administration on body composition, vascular function and structure in aged female rats.
Twelve female Wistar rats were ovariectomized at 10 months of age. At 20 months of age, half of the ovariectomized rats were treated with GH for 4 weeks. The remaining ovariectomized rats animals and one group of six intact females were used as control groups. After the treatment period, animals were sacrificed and Specific Gravity Index (SGI) and periuterine fat weigh, as well as vascular reactivity and morphometry in aortic rings, were studied.
No significant differences were found in SGI and periuterine fat weigh between ovariectomized and intact control rats. SGI was significantly increased by GH, and periuterine fat was reduced by the treatment. Dose-dependent relaxing responses to acetylcholine and isoproterenol were significantly diminished in ovariectomized rats as compared with intact animals, and GH treatment improved these responses. Ovariectomized animals showed significantly higher contracting responses to phenylephrine, acetylcholine + L-NAME and angiotensin-I than intact rats, and treatment with GH reduced them significantly. Media cross-sectional area was increased in ovariectomized rats as compared to intact animals, and GH reduced this area, but differences did not reach significance.
GH has beneficial effects in body composition and endothelial function in old ovariectomized female rats.
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ABSTRACT: The declining activity of the growth hormone--insulin-like growth factor I (IGF-I) axis with advancing age may contribute to the decrease in lean body mass and the increase in mass of adipose tissue that occur with aging. To test this hypothesis, we studied 21 healthy men from 61 to 81 years old who had plasma IGF-I concentrations of less than 350 U per liter during a six-month base-line period and a six-month treatment period that followed. During the treatment period, 12 men (group 1) received approximately 0.03 mg of biosynthetic human growth hormone per kilogram of body weight subcutaneously three times a week, and 9 men (group 2) received no treatment. Plasma IGF-I levels were measured monthly. At the end of each period we measured lean body mass, the mass of adipose tissue, skin thickness (epidermis plus dermis), and bone density at nine skeletal sites. In group 1, the mean plasma IGF-I level rose into the youthful range of 500 to 1500 U per liter during treatment, whereas in group 2 it remained below 350 U per liter. The administration of human growth hormone for six months in group 1 was accompanied by an 8.8 percent increase in lean body mass, a 14.4 percent decrease in adipose-tissue mass, and a 1.6 percent increase in average lumbar vertebral bone density (P less than 0.05 in each instance). Skin thickness increased 7.1 percent (P = 0.07). There was no significant change in the bone density of the radius or proximal femur. In group 2 there was no significant change in lean body mass, the mass of adipose tissue, skin thickness, or bone density during treatment. Diminished secretion of growth hormone is responsible in part for the decrease of lean body mass, the expansion of adipose-tissue mass, and the thinning of the skin that occur in old age.New England Journal of Medicine 08/1990; 323(1):1-6. · 51.66 Impact Factor
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ABSTRACT: Endothelium-derived substances and the renin-angiotensin system are important regulators of vascular tone. This study was designed to evaluate the effects of age and hypertension on vascular function of rat coronary arteries. Rings of the left anterior descending coronary artery were isolated from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at 12 (younger) and 72 (older) weeks of age and suspended in myographs (37 degrees C, 95% O2/5% CO2) for isometric tension recording. Systolic blood pressure was higher in SHR than in WKY rats (P < .05) but was unaffected by age in both strains. Active wall tension to KCl 100 mmol/L (mN/mm) was decreased in younger (0.28 +/- 0.03, n = 9) and older SHR (0.49 +/- 0.06, n = 13) compared with age-matched WKY rats (0.87 +/- 0.05, n = 9 and 1.51 +/- 0.11, n = 11, respectively, P < .05). In both strains, active wall tension to endothelin-1 and serotonin increased with age (n = 6 to 10, P < .05) but was decreased in younger and older SHR compared with WKY rats (P < .05). Active wall tension induced by angiotensin I 10(-7) mol/L was increased in older SHR (0.19 +/- 0.04, n = 7) compared with younger SHR (0.04 +/- 0.01, n = 9) but was similar in younger and older WKY rats (0.10 +/- 0.02 versus 0.15 +/- 0.03, n = 6 to 9) and younger SHR. In younger WKY rats and SHR, pretreatment of coronary arteries with benazeprilat 10(-5) mol/L (n = 5 for each) almost completely abolished the contractions to angiotensin I 10(-7) mol/L. Active wall tension to angiotensin II 10(-7) mol/L was comparable in all four groups, but compared with the contraction to KCl 100 mmol/L, the response was already increased in younger SHR (29 +/- 3%, n = 9) compared with the younger WKY rats (14 +/- 3%, n = 9, P < .05), but it was unaffected by age in both strains. In vitro treatment of younger WKY rat and SHR coronary arteries with the nonpeptide angiotensin II (AT1) receptor antagonist valsartan 10(-5) mol/L (n = 3 for each) fully suppressed contractions to angiotensin II 10(-7) mol/L. In contrast, endothelium-independent relaxations to the nitrovasodilator sodium nitroprusside, endothelium-dependent relaxations to acetylcholine, and endothelium-dependent contractions to N omega-nitro-L-arginine methyl ester were comparable in all four groups of rats. In summary, in rat coronary arteries, contractile responses to endothelin-1, serotonin, and KCl increase with age but are decreased by hypertension. In contrast, the L-arginine/nitric oxide pathway remains unaffected. The contractions to angiotensin I markedly increased with increasing duration of hypertension in the SHR only. Despite overall reduced contractile responses of SHR coronary arteries, contractions to angiotensin II were maintained. Hence, aging and hypertension affect contractile responses of rat coronary arteries to vasoconstrictor agonists differently.Circulation 06/1995; 91(9):2415-22. · 15.20 Impact Factor
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ABSTRACT: Carcass fat content was estimated in fed 12- and 19-day pregnant rats and fed and 48 hour starved virgin females following both specific gravity determination and direct gravimetry of extracted lipids. No change in body fat accumulation was found in 12-day pregnant rats whereas in 19-day pregnant animals it increased significantly. A significant correlation was also found when the percentage of carcass fat was plotted against specific gravity considering values from all subjects. Results indicate that in spite of reported maternal anabolic changes in the rat at midgestation fat accumulation occurs later in pregnancy when the mother has the highest food intake, which makes available sufficient substrates to support both fetal growth and body lipidic deposition.Life Sciences 11/1986; 39(15):1389-93. · 2.56 Impact Factor