دورية أكاديمية
Evidence for a noradrenergic mechanism causing hypertension and abnormal glucose metabolism in rats with relative deficiency of gamma-melanocyte-stimulating hormone.
العنوان: | Evidence for a noradrenergic mechanism causing hypertension and abnormal glucose metabolism in rats with relative deficiency of gamma-melanocyte-stimulating hormone. |
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المؤلفون: | Ni XP; Division of Nephrology, San Francisco General Hospital and Department of Medicine, University of California San Francisco, San Francisco, CA 94143-1341, USA., van Dijk C, Pearce D, Humphreys MH |
المصدر: | Experimental physiology [Exp Physiol] 2009 Aug; Vol. 94 (8), pp. 867-76. Date of Electronic Publication: 2009 May 08. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 9002940 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-445X (Electronic) Linking ISSN: 09580670 NLM ISO Abbreviation: Exp Physiol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Cambridge, Eng : Wiley-Blackwell Original Publication: Cambridge ; New York, NY, USA : Published for the Physiological Society by Cambridge University Press, c1990- |
مواضيع طبية MeSH: | Glucose/*metabolism , Hypertension/*etiology , Norepinephrine/*physiology , gamma-MSH/*deficiency, Animals ; Bromocriptine/pharmacology ; Heart Rate ; Hydralazine/pharmacology ; Insulin/blood ; Male ; Phentolamine/pharmacology ; Prolactin/blood ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride, Dietary/administration & dosage ; gamma-MSH/antagonists & inhibitors ; gamma-MSH/physiology |
مستخلص: | A close association between salt-sensitive hypertension and insulin resistance has been recognized for more than two decades, although the mechanism(s) underlying this relationship have not been elucidated. Recent data in mice with genetic disruption of the gamma-melanocyte-stimulating hormone (gamma-MSH) system suggest that this system plays a role in the pathophysiological relationship between hypertension and altered glucose metabolism during ingestion of a high-sodium diet (8% NaCl, HSD). We tested the hypothesis that these two consequences of interrupted gamma-MSH signalling were the result of sympathetic activation by studying rats treated with the dopaminergic agonist bromocriptine (5 mg kg(-1) i.p., daily for 1 week; Bromo) to cause relative gamma-MSH deficiency. Bromo-treated rats fed the HSD developed hypertension and also exhibited fasting hyperglycaemia (P < 0.005) and hyperinsulinaemia (P < 0.025). Furthermore, Bromo-treated rats on the HSD had impaired glucose tolerance and blunted insulin-mediated glucose disposal. Intravenous infusion of gamma(2)-MSH, or of the alpha-adrenergic receptor antagonist phentolamine, to Bromo-HSD rats lowered both mean arterial pressure (MAP) and blood glucose to normal after 15 min (P < 0.001 versus control), but had no effect in rats receiving vehicle and fed the HSD; gamma(2)-MSH infusion also reduced the elevated plasma noradrenaline to control levels in parallel with the reductions in MAP and blood glucose concentration. Infusion of hydralazine to Bromo-HSD rats lowered MAP but had only a trivial effect on blood glucose. We conclude that rats with relative gamma-MSH deficiency develop abnormal glucose metabolism, with features of insulin resistance, in association with hypertension when ingesting the HSD. Elevated plasma noradrenaline concentration in Bromo-HSD rats is normalized by gamma(2)-MSH infusion, suggesting that an adrenergic mechanism may link the salt-sensitive hypertension and the impaired glucose metabolism of relative gamma-MSH deficiency. |
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معلومات مُعتمدة: | R01 HL068871 United States HL NHLBI NIH HHS; R01 HL068871-05 United States HL NHLBI NIH HHS; HL68871 United States HL NHLBI NIH HHS |
المشرفين على المادة: | 0 (Insulin) 0 (Sodium Chloride, Dietary) 0 (gamma-MSH) 26NAK24LS8 (Hydralazine) 3A64E3G5ZO (Bromocriptine) 9002-62-4 (Prolactin) IY9XDZ35W2 (Glucose) X4W3ENH1CV (Norepinephrine) Z468598HBV (Phentolamine) |
تواريخ الأحداث: | Date Created: 20090512 Date Completed: 20091012 Latest Revision: 20211020 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC2853237 |
DOI: | 10.1113/expphysiol.2009.046748 |
PMID: | 19429645 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1469-445X |
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DOI: | 10.1113/expphysiol.2009.046748 |