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.

Nyckelord

Acetylcholine

pharmacology

Animals

Blood Pressure

physiology

Body Weight

Cardiac Output

Creatinine

blood

urine

Echocardiography

Endothelin-1

genetics

Insulin-Like Growth Factor I

deficiency

genetics

physiology

Liver

chemistry

Mesenteric Arteries

drug effects

Mice

Mice

Inbred C57BL

Mice

Inbred CBA

Mice

Knockout

Myocardium

chemistry

Nitric Oxide Synthase

antagonists & inhibitors

genetics

Nitric Oxide Synthase Type II

Nitric Oxide Synthase Type III

Norepinephrine

analysis

Organ Size

RNA

Messenger

analysis

Renin

blood

Vasodilation

drug effects

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