Submitted on July 11, 2006
Accepted on January 12, 2007
GHR deficiency in mice results in reduced systolic blood pressure and plasma renin, increased aortic eNOS expression and altered cardiovascular function
Emil Egecioglu1*, Irene J Andersson1, Entela Bollano2, Vilborg Palsdottir3, Britt G Gabrielsson4, John J. Kopchick5, Ole Skott6, Peter Bie7, Jorgen Isgaard2, Mohammad Bohlooly-Y8, Goran Bergstrom1, and Anna Wickman1
1 Department of Physiology, Sahlgrenska Academy, Göteborg University, Gothenburg, Sweden
2 Department of Clinical Physiology, Sahlgrenska Academy, Göteborg University, Gothenburg, Sweden
3 Department of Metabolism and Cardiovascular Research, Sahlgrenska Academy, Göteborg University, Gothenburg, Sweden
4 Gothenburg, United States; Department of Metabolism and Cardiovascular Research, Sahlgrenska Academy, Göteborg University, Gothenburg, Sweden
5 Edison Biotechnology Institute and Department of Biomedical Sciences, Ohio University, Athens, United States
6 Department of Physiology and Pharmacology, Institute of Medical Biology, Syddansk University, Odense, Denmark
7 Physiology and Pharmacology, University of Southern Denmark, Institute of Medical Biology, Odense C, Denmark
8 Astra Zeneca Molndal, United States
* To whom correspondence should be addressed. E-mail: emil.egecioglu{at}medic.gu.se.
To study the role of the growth hormone receptor (GHR) in the development of cardiovascular structure and function, female GHR gene disrupted or knock-out (KO) and wild type (WT) mice at the age of 18 weeks were used. GHR KO mice had lower plasma renin levels (P<0.05) and increased aortic eNOS expression (146%, P<0.05) accompanied by a 25% reduction in systolic blood pressure (BP, P<0.001) compared to 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 while 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 is beyond the observed alterations in body size. These data suggest an important role for an intact growth hormone/insulin-like growth factor-I axis in the maintenance of a normal cardiovascular system.
