| 1. |
- Andersson, Irene, 1978, et al.
(författare)
-
Reduced sympathetic responsiveness as well as plasma and tissue noradrenaline concentration in growth hormone transgenic mice
- 2004
-
Ingår i: Acta Physiol Scand. - 0001-6772. ; 182:4, s. 369-78
-
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.
|
|
| 2. |
|
|
| 3. |
- Egecioglu, Emil, 1977, et al.
(författare)
-
Growth hormone receptor deficiency in mice results in reduced systolic blood pressure and plasma renin, increased aortic eNOS expression, and altered cardiovascular structure and function
- 2007
-
Ingår i: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 292:5
-
Tidskriftsartikel (refereegranskat)abstract
- To study the role of the growth hormone receptor (GHR) in the development of cardiovascular structure and function, female GHR gene-disrupted or knockout (KO) and wild-type (WT) mice at age 18 wk were used. GHR KO mice had lower plasma renin levels (12 ± 2 vs. 20 ± 4 mGU/ml, P < 0.05) and increased aortic endothelial NO synthase (eNOS) expression (146%, P < 0.05) accompanied by a 25% reduction in systolic blood pressure (BP, 110 ± 4 vs. 147 ± 3 mmHg, P < 0.001) compared with WT mice. Aldosterone levels were unchanged, whereas the plasma potassium concentration was elevated by 14% ( P < 0.05) in GHR KO. Relative left ventricular weight was 14% lower in GHR KO mice ( P < 0.05), and cardiac dimensions as analyzed by echocardiography were similarly reduced. Myograph studies revealed a reduced maximum contractile response in the aorta to norepinephrine (NE) and K+ ( P < 0.05), and aorta media thickness was decreased in GHR KO ( P < 0.05). However, contractile force was normal in mesenteric arteries, whereas sensitivity to NE was increased ( P < 0.05). Maximal acetylcholine-mediated dilatation was similar in WT and GHR KO mice, whereas the aorta of GHR KO mice showed an increased sensitivity to acetylcholine ( P < 0.05). In conclusion, loss of GHR leads to low BP and decreased levels of renin in plasma as well as increase in aortic eNOS expression. Furthermore, GHR deficiency causes functional and morphological changes in both heart and vasculature that are beyond the observed alterations in body size. These data suggest an important role for an intact GH/IGF-I axis in the maintenance of a normal cardiovascular system.
|
|
| 4. |
- Fredholm, BB, et al.
(författare)
-
Consequences of eliminating adenosine A(1) receptors in mice
- 2003
-
Ingår i: Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 1). - : Wiley. - 1098-2299 .- 0272-4391. ; 58, s. 350-
-
Konferensbidrag (refereegranskat)abstract
- The second coding exon of the adenosine A, receptor gene was eliminated by homologous recombination. The phenotype of mice (mixed C57B6/129OlaHsd background) was studied, using siblings from matings of heterozygous mice. Among the offspring the ratio between+/+, +/-and -/-animals was 1:2:1. Over the first half-year-at least-growth and viability were the same in all genotypes. Binding of A(1) ligands was eliminated in-/-mice and halved in+/-mice. Blood pressure was increased in-/-mice and this was paralleled by an increase in plasma renin. Heart rate was unaffected, as was contractility. Furthermore, the response of the perfused heart to ischemia was similar in+/+and -/-hearts. However, remote preconditioning was eliminated in-/-mouse hearts. Tubuloglomerular feedback in the kidney was also lost in-/-mice. The analgesic response to a non-selective adenosing receptor agonist was lost in-/-mice, which also showed hyperalgesia in the tail-flick test. There was a slight hypoactivity in-/-mice, but responses to caffeine were essentially normal. The inhibition of excitatory neurotransmission in hippocampus by adenosine was lost in-/-mice and reduced in+/-mice. Responses to ATP were affected similarly. Hypoxic depression of synaptic transmission was essentially eliminated in hippocampus and hypoxic decrease in spinal respiratory neuron firing was markedly reduced. These results show that adenosine A, receptors play a physiologically important role in the kidney, spinal cord, and hippocampus and that they are critically important in the adaptive responses to hypoxia. (C) 2003 Wiley-Liss, Inc.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Johansson, Maria E, 1977, et al.
(författare)
-
Blood pressure is the major driving force for plaque formation in aortic-constricted ApoE-/- mice
- 2006
-
Ingår i: Journal of Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352. ; 24:10, s. 2001-8
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Using an aortic constriction model in mice, we studied whether the increase in pressure or the activation of the renin-angiotensin system (RAS) and its main receptors is the main driving force for plaque progression. METHODS: Male ApoE mice underwent sham surgery or placement of a suprarenal silver clip around the aorta (AoC). Half the group was treated with the selective AT1 receptor antagonist losartan (30 mg/kg per day) for 4 weeks. RESULTS: Anesthetized mean arterial pressure (MAP) was increased in AoC mice compared to sham (106 +/- 3 versus 90 +/- 1 mmHg, P < 0.001). Losartan reduced MAP in sham mice (78 +/- 2 mmHg, P < 0.01) but not in AoC (AoC losartan 104 +/- 2 mmHg). Plasma renin concentration (PRC) was increased in AoC mice compared to sham [1.6 +/- 0.3 versus 0.8 +/- 0.2 milliGoldblatt units (mGU)/ml, P < 0.001]. Losartan treatment augmented this difference (18.7 +/- 3.7 versus 4.6 +/- 1.7 mGU/ml, P < 0.01). AT2 receptor mRNA expression was increased 5.8-fold by aortic constriction in thoracic aorta (P < 0.05) and the major site for expression of the AT2 receptor protein was within the plaques. The plaque area was increased in AoC mice compared to sham (0.61 +/- 0.09 versus 0.07 +/- 0.01%, P < 0.001); however, losartan did not alter plaque area. CONCLUSIONS: Our data do not support a role for the AT1 receptor in the progression of atherosclerosis in this model, since blockade with losartan did not alter plaque distribution. Furthermore, we found no support for the counteraction of atherogenesis by increased activity of the RAS acting on the AT2 receptor. Our data suggest that increased pressure is the main driving force for atherosclerosis in this model.
|
|
| 8. |
- Larsson, A, et al.
(författare)
-
Dental health of patients with X-linked hypophosphatemia: A controlled study
- 2023
-
Ingår i: Frontiers in oral health. - : Frontiers Media SA. - 2673-4842. ; 4, s. 1087761-
-
Tidskriftsartikel (refereegranskat)abstract
- The present study compared the dental health of patients with X-linked hypophosphatemia (XLH) with healthy age- and gender-matched controls to increase our knowledge of the impact of XLH on oral health.Materials and methodsTwenty-two adult patients with XLH in the Stockholm region of Sweden were referred to the Department of Orofacial Medicine at Karolinska Institutet for an extended clinical and radiological examination. Pre-existing radiologic examinations of 44 healthy age- and gender-matched controls were retrieved from the Department of Oral Radiology, at Karolinska Institutet.ResultsThe 22 patients with XLH (15 females, median age 38 years, range 20–71; 7 males, median age 49 years, range 24–67) had a significantly higher number of root-filled teeth compared to healthy controls (p = .001). In the XLH group, females had significantly better oral health than males, especially concerning endodontic and cariological status (p's = .01 and .02, respectively). Periodontal status differed non-significantly between the XLH and control groups.ConclusionPatients with XLH had a significantly lower oral health status compared to a healthy population especially concerning endodontic conditions. Male patients with XLH had a higher risk of poor oral health compared to female patients with XLH.
|
|
| 9. |
|
|
| 10. |
|
|
