title: Disrupted regulation of ghrelin production under antihypertensive treatment in spontaneously hypertensive rats.
abstract: BACKGROUND
  Ghrelin is an acylated peptide hormone mainly secreted from the stomach. When administrated externally it modulates vascular tone mainly through the regulation of autonomic nerve activity. However, the effects of blood pressure (BP) on the production and secretion of ghrelin remain to be clarified.
  
  
  RESULTS
  We examined the stomach and plasma levels of ghrelin in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats after a 4-week-intervention with antihypertensive agents (candesartan-cilexetil [ARB], doxazosin [DZN], metoprolol [MP], reserpine [RES]) to clarify the influence of BP on the secretion of ghrelin. The effect of these agents on ghrelin production and secretion were examined by comparing vehicle-treated controls (WKY-Intact, SHR-Intact). Treatment with the 4 antihypertensive drugs all yielded a significant decline in systolic BP in both SHR and WKY. Under these conditions, significantly lower levels of stomach and plasma ghrelin were detected in WKY treated with ARB (P<0.05), DZN (P<0.05), MP (P<0.05) and RES (P<0.05) compared with WKY-Intact, whereas no significant change in the ghrelin levels in the stomach and plasma were detected in SHR under the same treatments.
  
  
  CONCLUSIONS
  The findings imply that the production and secretion of ghrelin are controlled by the ambient vascular tone and vice versa in normotensive WKY. This inter-relationship between ghrelin and BP seems to be disrupted in SHR.
authors.affiliation: Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan.
authors.forename: Naokazu
authors.initials: N
authors.lastname: Hamada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tajiri
authors.forename: Kentaro
authors.initials: K
authors.lastname: Setoyama
authors.forename: Ryozo
authors.initials: R
authors.lastname: Kamimura
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Miyahara
authors.forename: Norihito
authors.initials: N
authors.lastname: Nuruki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoda
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Masayasu
authors.initials: M
authors.lastname: Kojima
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Mifune
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D017292:Doxazosin / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism; D005786:Gene Expression Regulation; D054439:Ghrelin / Q000097:blood* / Q000235:genetics; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007333:Insulin Resistance; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012110:Reserpine / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D058671:Adrenergic beta-1 Receptor Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D054439:Ghrelin; D012333:RNA, Messenger; D013777:Tetrazoles; D014665:Vasodilator Agents; D012110:Reserpine; D008790:Metoprolol; D017292:Doxazosin; C077793:candesartan cilexetil; D009638:Norepinephrine