Reduced sympathetic responsiveness as well as plasma and tissue noradrenaline concentration in growth hormone transgenic mice

• AIMS: Acromegaly [overproduction of growth hormone (GH)] and GH deficiency have both been associated with alterations in autonomic nervous system function. The aim of this study was to investigate autonomic nervous system influence on heart rate (HR) in transgenic mice overexpressing bovine GH (bGH). METHODS: HR and HR variability (HRV) were measured in conscious young (8-13 weeks) and old (5-6 months) female bGH and control mice using telemetry. HR control was studied using antagonists and an agonist of adrenergic and muscarinic receptors. Noradrenaline was measured in plasma, heart and kidney using high performance liquid chromatography. RESULTS: Average 24 h resting HR did not differ between bGH and control mice. After saline injection and after muscarinic blockade with methylscopolamine HR increase was blunted (in old) or absent (in young) bGH mice compared with control mice (P < 0.05). Phenylephrine caused a baroreflex mediated decrease in HR from around 550 to 300-350 beats min(-1), not different between bGH and control mice. Time- and frequency-domain measures of HRV were reduced in old bGH compared with control mice (P < 0.05). Noradrenaline concentrations were reduced by 25-49% in plasma and tissue of bGH compared with control mice (P < 0.05). CONCLUSION: The current study suggests reduced autonomic modulation of HR in bGH transgenic mice. Thus, GH appears to have marked effects on autonomic tone, reducing sympathetic nervous system function possibly via reduced noradrenaline stores.

Nyckelord

Acromegaly/metabolism/pathology/*physiopathology

Aging/physiology

Animals

Body Weight

Cattle

Circadian Rhythm

Female

Growth Hormone/genetics/*physiology

Heart Rate

Kidney/pathology

Mice

Mice

Transgenic

Norepinephrine/blood/*metabolism

Organ Size

Parasympathetic Nervous System/physiopathology

Renin/blood

Sympathetic Nervous System/*physiopathology

Telemetry

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)