title: Ghrelin counteracts salt-induced hypertension via promoting diuresis and renal nitric oxide production in Dahl rats.
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.
authors: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan.
authors: Hirotaka
authors: H
authors: Aoki
authors: Masanori
authors: M
authors: Nakata
authors: Katsuya
authors: K
authors: Dezaki
authors: Ming
authors: M
authors: Lu
authors: Darambazar
authors: D
authors: Gantulga
authors: Keiji
authors: K
authors: Yamamoto
authors: Kazuyuki
authors: K
authors: Shimada
authors: Kazuomi
authors: K
authors: Kario
authors: Toshihiko
authors: T
authors: Yada
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004231:Diuresis / Q000187:drug effects*; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004790:Enzyme Induction / Q000187:drug effects; D054439:Ghrelin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism* / Q000652:urine; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000097:blood / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D012964:Sodium / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000009:adverse effects; D014463:Ultrasonography; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D004232:Diuretics; D054439:Ghrelin; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; C472610:atrial natriuretic peptide, rat; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D012964:Sodium; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat