Growth hormone receptor deficiency in mice results in reduced systolic blood pressure and plasma renin, increased aortic eNOS expression, and altered cardiovascular structure and function

E Egecioglu, I J Andersson, E Bollano, V Palsdottir, B G Gabrielsson, J J Kopchick, Ole Skøtt, P Bie, J Isgaard, M Bohlooly-Y, G Bergström, A Wickman

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

To study the role of the growth hormone receptor (GHR) in the development of cardiovascular structure and function, female GHR gene-disrupted or knockout (KO) and wild-type (WT) mice at age 18 wk were used. GHR KO mice had lower plasma renin levels (12 +/- 2 vs. 20 +/- 4 mGU/ml, P < 0.05) and increased aortic endothelial NO synthase (eNOS) expression (146%, P < 0.05) accompanied by a 25% reduction in systolic blood pressure (BP, 110 +/- 4 vs. 147 +/- 3 mmHg, P < 0.001) compared with WT mice. Aldosterone levels were unchanged, whereas the plasma potassium concentration was elevated by 14% (P < 0.05) in GHR KO. Relative left ventricular weight was 14% lower in GHR KO mice (P < 0.05), and cardiac dimensions as analyzed by echocardiography were similarly reduced. Myograph studies revealed a reduced maximum contractile response in the aorta to norepinephrine (NE) and K(+) (P < 0.05), and aorta media thickness was decreased in GHR KO (P < 0.05). However, contractile force was normal in mesenteric arteries, whereas sensitivity to NE was increased (P < 0.05). Maximal acetylcholine-mediated dilatation was similar in WT and GHR KO mice, whereas the aorta of GHR KO mice showed an increased sensitivity to acetylcholine (P < 0.05). In conclusion, loss of GHR leads to low BP and decreased levels of renin in plasma as well as increase in aortic eNOS expression. Furthermore, GHR deficiency causes functional and morphological changes in both heart and vasculature that are beyond the observed alterations in body size. These data suggest an important role for an intact GH/IGF-I axis in the maintenance of a normal cardiovascular system.
Original languageEnglish
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Volume292
Issue number5
Pages (from-to)E1418-E1425
Number of pages7
ISSN0193-1849
DOIs
Publication statusPublished - 1. May 2007

Keywords

  • Aldosterone
  • Animals
  • Aorta, Thoracic
  • Blood Pressure
  • Cardiovascular Physiology
  • Cardiovascular System
  • Echocardiography, Doppler
  • Electrocardiography
  • Female
  • Heart
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Muscle Contraction
  • Nitric Oxide Synthase Type II
  • Organ Size
  • Potassium
  • RNA, Messenger
  • Receptors, Somatotropin
  • Renin
  • Reverse Transcriptase Polymerase Chain Reaction

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