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The interplay between the endocrine and cardiovascular systems. A study of the hormonal influence on cardiovascular function and endothelial nitric oxide synthase (eNOS) expression

Författare och institution:
Anna Wickman (Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi)
Datum för examination:
Fysiologiska avdelningens föreläsningssal, F1405 ("Inge Schiöler"), kl. 09.00
Sammanfattning (abstract):
During the present thesis, special interest was focused on the cardiovascular effects of growth hormone (GH) and estrogen (E2) and combined treatment of GH+E2, in particular the possible effects on endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) bioavailability for maintaining cardiovascular homeostasis. The possible role of fluid mechanical force e.g. shear stress, pressure and flow, which may influence eNOS expression in the two kidney-one clip (2K1C) hypertensive rat model, was also studied. The importance of an intact NO system for developing cardiovascular hypertrophy was studied by using L-NAME, an NO synthase blockade.In hormonal treated (GH, thyroxine (T4), glucocorticoids (GC), insulin-like growth factor-I (IGF-I), E2, GH+E2) hypophysectomized (Hx) female rats, the cardiovascular function (blood pressure (BP) and heart rate (HR)) was explored. Hypophysectomy resulted in a fall in BP and HR. None of the hormones affected BP. Both GH and IGF-I increased HR, while T4+GC, E2 or GH+E2 had no effect on HR. The regulation of GH and IGF-I on eNOS expression in the aorta, caval vein and heart was investigated using immunoblotting. GH and IGF-I increased eNOS expression in the aorta, while caval vein and heart were unaffected. The vascular contractile properties and endothelial function were studied in mesenteric arteries after treatment with E2, GH or GH+E2 using wire-myograph technique. After Hx, impaired acetylcholine-induced relaxation and NO release were shown, suggesting endothelial dysfunction, while the adrenergic response was enhanced. None of the hormones affected the impaired adrenergic response or endothelial dysfunction. The eNOS expression in the medulla and cortex of the kidneys from the 2K1C rats, before and after removal of the clip (unclipping), was studied by immunoblotting. The effects of aldosterone and angiotensin II infusion on medullary eNOS protein were tested, as well as the effect of L-NAME on medullary blood flow. Similar levels of eNOS were seen in the left and right kidneys at all time points. Endothelial NOS expression was reduced in the medulla in 2K1C and 3 hours after unclipping. However, 48 hours and 4 weeks after unclipping, the levels returned to normotensive values. Cortical eNOS was increased in kidneys from 2K1C rats during all time points. Neither angiotensin II nor aldosterone affected eNOS expression in the medulla. Medullary blood flow was under similar influence of NO in both 2K1C and normotensive kidneys.Twelve days of L-NAME treatment was studied to determine if this would cause a growth-inhibitory response in the heart and vessels. L-NAME treatment resulted in increased BP with no associated left ventricular (LV) hypertrophy. There was no expected over-expression of IGF-I mRNA in either LV or the aorta measured by solution hybridisation. The vasculature bed showed structural up ward auto-regulation, mainly in terms of increased medial mass. Altogether, these findings support a positive role for GH/IGF-I in the regulation and improvement of endothelial function in the aorta. It seems that none of these hormones (T4, GC, GH, E2) can improve endothelial function or vascular reactivity of small mesenteric arteries. The NO system seems to play an important role in the regulation of cardiovascular function. A reduced eNOS level may be of patho-physiological importance in development of renal hypertension. An intact NO system is needed to create an adaptive growth response in the cardiovascular system. In conclusion, a functional interplay between endocrine and cardiovascular systems is needed to create an adequate cardiovascular homeostasis.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
hypophysectomy · growth hormone · insulin-like growth factor-I · estrogen · vascular reactivity · endothelial function · endothelial nitric oxide synthase · nitric oxide · cardiovascular function · vasculature · kidney · hypertension
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Postens nummer:
Posten skapad:
2011-02-17 14:21

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