Liver-derived insulin-like growth factor-I is involved in the regulation of blood pressure in mice.
IGF-I has been suggested to be of importance for cardiovascular structure and function, but the relative role of locally produced and liver-derived endocrine IGF-I remains unclear. Using the Cre-LoxP recombination system, we have previously created transgenic mice with a liver-specific, inducible IGF-I knockout (LI-IGF-I-/-). To examine the role of liver-derived IGF-I in cardiovascular physiology, liver-derived IGF-I was inactivated at 4 wk of age, resulting in a 79% reduction of serum IGF-I levels. At 4 months of age, systolic blood pressure (BP) was increased in LI-IGF-I-/- mice. Echocardiography showed increased posterior wall thickness in combination with decreased stroke volume and cardiac output, whereas other systolic variables were unchanged, suggesting that these cardiac effects were secondary to increased peripheral resistance. Acute nitric oxide-synthase inhibition increased systolic BP more in LI-IGF-I-/- mice than in control mice. LI-IGF-I-/- mice showed impaired acetylcholine-induced vasorelaxation in mesenteric resistance vessels and increased levels of endothelin-1 mRNA in aorta. Thus, the increased peripheral resistance in LI-IGF-I-/- mice might be attributable to endothelial dysfunction associated with increased expression of endothelin-1 and impaired vasorelaxation of resistance vessels. In conclusion, our findings suggest that liver-derived IGF-I is involved in the regulation of BP in mice.
Tivesten
Asa
A
Research Center for Endocrinology and Metabolism, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. asa.tivesten@medic.gu.se
Bollano
Entela
E
Andersson
Irene
I
Fitzgerald
Sharyn
S
Caidahl
Kenneth
K
Sjögren
Klara
K
Skøtt
Ole
O
Liu
Jun-Li
JL
Mobini
Reza
R
Isaksson
Olle G P
OG
Jansson
John-Olov
JO
Ohlsson
Claes
C
Bergström
Göran
G
Isgaard
Jörgen
J
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D001835:Body Weight; D002302:Cardiac Output; D003404:Creatinine / Q000097:blood / Q000652:urine; D004452:Echocardiography; D019332:Endothelin-1 / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000737:chemistry*; D008638:Mesenteric Arteries / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009206:Myocardium / Q000737:chemistry; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009638:Norepinephrine / Q000032:analysis; D009929:Organ Size; D012333:RNA, Messenger / Q000032:analysis; D012083:Renin / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
D019332:Endothelin-1; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003404:Creatinine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D012083:Renin; D000109:Acetylcholine; D009638:Norepinephrine