Ghrelin counteracts salt-induced hypertension via promoting diuresis and renal nitric oxide production in Dahl rats

  • Aoki Hirotaka
    Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan Depertment of Internal medicine, Division of Cardiovascular Medicine, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan
  • Nakata Masanori
    Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan
  • Dezaki Katsuya
    Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan
  • Lu Ming
    Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan
  • Gantulga Darambazar
    Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan
  • Yamamoto Keiji
    Depertment of Internal medicine, Division of Cardiovascular Medicine, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan Department of General Internal Medicine, Saitama Medical School, Saitama 350-0495, Japan
  • Shimada Kazuyuki
    Depertment of Internal medicine, Division of Cardiovascular Medicine, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan
  • Kario Kazuomi
    Depertment of Internal medicine, Division of Cardiovascular Medicine, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan
  • Yada Toshihiko
    Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan

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Abstract

Ghrelin is the endogenous ligand for the growth hormone-secretagogue receptor expressed in various tissues including the heart, blood vessels and kidney. This study sought to determine the effects of long-term treatment with ghrelin (10 nmol/kg, twice a day, intraperitoneally) on the hypertension induced by high salt (8.0% NaCl) diet in Dahl salt-sensitive hypertensive (DS) rats. Systolic blood pressure (SBP) was measured by a tail cuff method. During the treatment period for 3 weeks, high salt diet increased blood pressure compared to normal salt (0.3% NaCl) diet, and this hypertension was partly but significantly (P<0.01) attenuated by simultaneous treatment with ghrelin. Ghrelin significantly increased urine volume and tended to increase urine Na+ excretion. Furthermore, ghrelin increased urine nitric oxide (NO) excretion and tended to increase renal neuronal nitric oxide synthase (nNOS) mRNA expression. Ghrelin did not alter the plasma angiotensin II level and renin activity, nor urine catecholamine levels. Furthermore, ghrelin prevented the high salt-induced increases in heart thickness and plasma ANP mRNA expression. These results demonstrate that long-term ghrelin treatment counteracts salt-induced hypertension in DS rats primarily through diuretic action associated with increased renal NO production, thereby exerting cardio-protective effects.

Journal

  • Endocrine Journal

    Endocrine Journal 60 (5), 571-581, 2013

    The Japan Endocrine Society

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