Growth hormone-induced blood pressure decrease is associated with increased mRNA levels of the vascular smooth muscle KATP channel.

• Growth hormone (GH) deficiency is associated with abnormal vascular reactivity and development of atherosclerosis. GH treatment in GH deficient states restores systemic vascular resistance, arterial compliance, endothelium-dependent and endothelium-independent vasodilation, and may reverse markers of early atherosclerosis. However, very little is known about the molecular mechanisms underlying these effects. In the present study, male Sprague Dawley rats were hypophysectomized and treated for two weeks with GH (recombinant human GH, 2 mg/kg/day) or saline as s.c. injections twice daily. GH decreased aortic systolic blood pressure compared with saline-treated animals, while the diastolic blood pressure was not significantly changed. GH treatment increased cardiac output as determined by Doppler-echocardiography and the calculated systemic vascular resistance was markedly reduced. In order to identify GH-regulated genes of importance for vascular function, aortic mRNA levels were analyzed by the microarray technique and correlated to the systolic blood pressure levels. Using this approach, we identified 18 GH-regulated genes with possible impact on vascular tone and atherogenesis. In particular, mRNA levels of the inwardly rectifying potassium channel Kir6.1 and the sulfonylurea receptor 2B, which together form the vascular smooth muscle ATP-sensitive potassium channel, were both up-regulated by GH treatment and highly correlated to systolic blood pressure. Our findings establish a major role for GH in the regulation of vascular physiology and gene expression. Increased expression of the ATP-sensitive potassium channel, recently shown to be crucial in the regulation of vascular tone, constitutes a possible mechanism by which GH governs vascular tone.

Nyckelord

ATP-Binding Cassette Transporters

genetics

Animals

Aorta

Blood Pressure

drug effects

Cardiac Output

drug effects

Gene Expression

drug effects

Human Growth Hormone

pharmacology

Hypophysectomy

Male

Microarray Analysis

Muscle

Smooth

Vascular

metabolism

Na(+)-K(+)-Exchanging ATPase

genetics

metabolism

Potassium Channels

genetics

Potassium Channels

Inwardly Rectifying

genetics

RNA

Messenger

analysis

Rats

Rats

Sprague-Dawley

Receptors

Drug

genetics

Recombinant Proteins

pharmacology

Systole

Vascular Resistance

drug effects

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)