| 1. |
- Hägg Samuelsson, Ulrika, 1973, et al.
(författare)
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Voluntary physical exercise-induced vascular effects in spontaneously hypertensive rats
- 2004
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Ingår i: Clin Sci (Lond). - 0143-5221. ; 107:6, s. 571-81
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Tidskriftsartikel (refereegranskat)abstract
- Forced training has been shown to have beneficial vascular effects in various animal exercise models. In the present study, we explored possible physiological and molecular effects of voluntary physical exercise on various vascular beds. SHR (spontaneously hypertensive rats) performed voluntary exercise for 5 weeks in a computerized wheel cage facility. Ex vivo myograph studies revealed an increased sensitivity of the ACh (acetylcholine)-mediated vasodilation in resistance arteries of the exercised animals (ED50=15.0+/-3.5 nmol/l) compared with the controls (ED50=37.0+/-8.8 nmol/l; P=0.05). The exercise/control difference was abolished after scavenging reactive oxygen radicals. In conduit arteries, ACh induced a similar vasodilatory response in both groups. The in vivo aortic wall stiffness, assessed by means of Doppler tissue echography, was significantly lower in the exercising animals than in controls. This was demonstrated by significantly increased peak systolic aortic wall velocity (P=0.03) and the velocity time integral (P=0.01) in exercising animals compared with controls. The relative gene expression of eNOS (endothelial nitric oxide synthase) was similar in both groups of animals, whereas Cu/ZnSOD (copper/zinc superoxide dismutase) gene expression was significantly increased (+111%; P=0.0007) in the exercising animal compared with controls. In conclusion, voluntary physical exercise differentially improves vascular function in various vascular beds. Increased vascular compliance and antioxidative capacity may contribute to the atheroprotective effects associated with physical exercise in conduit vessels.
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| 2. |
- Andersson, Irene, 1978
(författare)
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Cardiovascular effects of growth hormone. Studies in genetically engineered mice
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this thesis was to enhance the understanding on the relationships between growth hormone (GH) and cardiovascular disease using genetically engineered mice. More specifically the effects of GH on blood pressure (BP), vascular and cardiac function, atherosclerosis and autonomic control of heart rate were studied. Two genetically engineered mice models were used, bovine GH transgenic (bGH) and GH receptor/binding protein knock-out mice (GHR KO). In addition a third mouse model was generated through crossbreeding of bGH and an atherosclerosis prone mouse strain, apoE-/-, yielding apoE-/-/bGH mice. bGH mice had increased mean arterial BP compared to control mice as measured by telemetry. The hypertension was not salt sensitive but associated with increased resistance of the hindquarter vasculature. Mesenteric arteries from bGH mice displayed intact endothelial function and decreased sensitivity to noradrenaline, as assessed by myograph technique, while carotid artery and aorta displayed impaired endothelial function. Treatment of the vessels with a super oxide dismutase (SOD) mimetic appeared to abolish differences in endothelium dependent vasodilation between bGH and control mice. However, aorta from young bGH mice had intact endothelial function accompanied by increased mRNA levels of SOD and endothelial nitric oxide synthase, semi quantified by real-time PCR. Heart rate responses measured by telemetry, to pharmacological challenging of the sympathetic and parasympathetic nervous system, showed that bGH mice had reduced ability for sympathetic activation but intact reflex activation of parasympathetic nervous system. bGH mice also had decreased heart rate variability and reduced noradrenaline concentrations in plasma and tissue, measured by high performance liquid chromatography. Systolic BP, measured by tail-cuff technique, was increased in female apoE-/-/bGH mice compared to apoE-/- control mice. Atherosclerotic plaque area in the thoracic aorta, quantified en face after lipid staining, was significantly increased in male apoE-/-/bGH compared to control, and tended to be increased in female apoE-/-/bGH. Interestingly, female apoE-/-/bGH had a more atherogenic serum lipid profile than male. Finally, GHR KO mice had decreased systolic BP measured by tail-cuff technique and reduced cardiac and vascular structure but intact endothelial function. Furthermore, GHR KO mice had impaired cardiac function as assessed by echocardiography. In summary, this thesis has generated new knowledge on the effects of GH on cardiovascular function and development of atherosclerosis. It has presented a novel mouse model that facilitates direct studies on the mechanism involved in GH induced atherogenesis. A further important finding is that GH appears to have profound effects on sympathetic nervous system function and tissue noradrenaline levels. This may be an interesting future target for treatment of diseases associated with autonomic dysfunction.
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| 3. |
- Andersson, Irene, 1978, et al.
(författare)
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Reduced sympathetic responsiveness as well as plasma and tissue noradrenaline concentration in growth hormone transgenic mice
- 2004
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Ingår i: Acta Physiol Scand. - 0001-6772. ; 182:4, s. 369-78
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Acromegaly [overproduction of growth hormone (GH)] and GH deficiency have both been associated with alterations in autonomic nervous system function. The aim of this study was to investigate autonomic nervous system influence on heart rate (HR) in transgenic mice overexpressing bovine GH (bGH). METHODS: HR and HR variability (HRV) were measured in conscious young (8-13 weeks) and old (5-6 months) female bGH and control mice using telemetry. HR control was studied using antagonists and an agonist of adrenergic and muscarinic receptors. Noradrenaline was measured in plasma, heart and kidney using high performance liquid chromatography. RESULTS: Average 24 h resting HR did not differ between bGH and control mice. After saline injection and after muscarinic blockade with methylscopolamine HR increase was blunted (in old) or absent (in young) bGH mice compared with control mice (P < 0.05). Phenylephrine caused a baroreflex mediated decrease in HR from around 550 to 300-350 beats min(-1), not different between bGH and control mice. Time- and frequency-domain measures of HRV were reduced in old bGH compared with control mice (P < 0.05). Noradrenaline concentrations were reduced by 25-49% in plasma and tissue of bGH compared with control mice (P < 0.05). CONCLUSION: The current study suggests reduced autonomic modulation of HR in bGH transgenic mice. Thus, GH appears to have marked effects on autonomic tone, reducing sympathetic nervous system function possibly via reduced noradrenaline stores.
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| 4. |
- Tivesten, Åsa, 1969, et al.
(författare)
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Liver-derived insulin-like growth factor-I is involved in the regulation of blood pressure in mice.
- 2002
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Ingår i: Endocrinology. - 0013-7227. ; 143:11, s. 4235-42
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Tidskriftsartikel (refereegranskat)abstract
- IGF-I has been suggested to be of importance for cardiovascular structure and function, but the relative role of locally produced and liver-derived endocrine IGF-I remains unclear. Using the Cre-LoxP recombination system, we have previously created transgenic mice with a liver-specific, inducible IGF-I knockout (LI-IGF-I-/-). To examine the role of liver-derived IGF-I in cardiovascular physiology, liver-derived IGF-I was inactivated at 4 wk of age, resulting in a 79% reduction of serum IGF-I levels. At 4 months of age, systolic blood pressure (BP) was increased in LI-IGF-I-/- mice. Echocardiography showed increased posterior wall thickness in combination with decreased stroke volume and cardiac output, whereas other systolic variables were unchanged, suggesting that these cardiac effects were secondary to increased peripheral resistance. Acute nitric oxide-synthase inhibition increased systolic BP more in LI-IGF-I-/- mice than in control mice. LI-IGF-I-/- mice showed impaired acetylcholine-induced vasorelaxation in mesenteric resistance vessels and increased levels of endothelin-1 mRNA in aorta. Thus, the increased peripheral resistance in LI-IGF-I-/- mice might be attributable to endothelial dysfunction associated with increased expression of endothelin-1 and impaired vasorelaxation of resistance vessels. In conclusion, our findings suggest that liver-derived IGF-I is involved in the regulation of BP in mice.
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