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Hypertension plus diabetes mimics the cardiomyopathy induced by nitric oxide inhibition in rats.

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  • معلومة اضافية
    • المصدر:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0231335 Publication Model: Print Cited Medium: Print ISSN: 0012-3692 (Print) Linking ISSN: 00123692 NLM ISO Abbreviation: Chest Subsets: MEDLINE
    • بيانات النشر:
      Publication: 2016- : New York : Elsevier
      Original Publication: Chicago : American College of Chest Physicians
    • الموضوع:
      Cardiomyopathy, Hypertrophic/*etiology ; Diabetes Mellitus, Experimental/*complications ; Hypertension, Renovascular/*complications ; Myocardium/*pathology ; Nitric Oxide/*antagonists & inhibitors ; Nitric Oxide Synthase/*biosynthesis; Analysis of Variance ; Animals ; Blotting, Western ; Cardiomyopathy, Hypertrophic/pathology ; Disease Models, Animal ; Immunohistochemistry ; Male ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide/biosynthesis ; Nitric Oxide Synthase/analysis ; Organ Size ; Probability ; Random Allocation ; Rats ; Rats, Wistar ; Streptozocin/pharmacology
    • نبذة مختصرة :
      Study Objectives: We compared the myocardial lesions caused by the long-term inhibition of nitric oxide (NO) biosynthesis with those associated with renovascular hypertension (two-kidney, one-clip model [2K-1C]) and superimposed streptozotocin-induced diabetes mellitus (DM).
      Design: Prospective trial.
      Setting: University laboratory.
      Interventions: Male Wistar rats were classified into the following groups: (1) a control group; (2) the L-NAME group (treatment with the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester [L-NAME], 75 micro mol per rat per day, orally); (3) the 2K-1C group (renovascular hypertension); (4) the DM group (treatment with streptozotocin, 60 mg/kg via intraperitoneal route); and (5) the 2K-1C plus DM group (renovascular hypertension and streptozotocin-induced DM). Arterial BP was measured by a tail-cuff method for 3 weeks, after which histologic and stereological analysis of the heart was done and cardiac NO synthase type 3 (NOS3) levels were assessed by Western blotting. The circulating levels of nitrates/nitrites and thromboxane B(2) (TXB(2), the stable metabolite of thromboxane A(2)) were also measured.
      Results: In DM and 2K-1C rats, the myocardial lesions consisted mainly of recent myocardial infarcts, which were more severe in the 2K-1C plus DM group. In L-NAME-treated rats, multiple foci of reparative fibrosis and fresh myocardial necrosis resembled the severe lesions found in the 2K-1C plus DM group. Although NOS3 protein expression increased (19 to 44%; p < 0.05) in all treated groups, serum nitrate/nitrite levels decreased only in the L-NAME group and the 2K-1C plus DM group. These two groups also showed a more pronounced increase in TXB(2) concentrations.
      Conclusions: These results indicate that the association of hypertension and DM mimics the alterations induced by L-NAME in rats, which suggests a role for NO in the pathophysiology of hypertensive-diabetic cardiomyopathy.
    • الرقم المعرف:
      31C4KY9ESH (Nitric Oxide)
      5W494URQ81 (Streptozocin)
      EC 1.14.13.39 (Nitric Oxide Synthase)
      V55S2QJN2X (NG-Nitroarginine Methyl Ester)
    • الموضوع:
      Date Created: 20021016 Date Completed: 20021122 Latest Revision: 20190514
    • الموضوع:
      20250114
    • الرقم المعرف:
      10.1378/chest.122.4.1412
    • الرقم المعرف:
      12377873