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Evidence for a noradrenergic mechanism causing hypertension and abnormal glucose metabolism in rats with relative deficiency of γ‐melanocyte‐stimulating hormone
Author(s) -
Ni XiPing,
Van Dijk Claudia,
Pearce David,
Humphreys Michael H.
Publication year - 2009
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2009.046748
Subject(s) - endocrinology , medicine , mechanism (biology) , carbohydrate metabolism , melanocyte stimulating hormone , hormone , metabolism , philosophy , epistemology
A close association between salt‐sensitive hypertension and insulin resistance has been recognized for more than two decades, although the mechanism(s) underlying this relationship have not been elucidated. Recent data in mice with genetic disruption of the γ‐melanocyte‐stimulating hormone (γ‐MSH) system suggest that this system plays a role in the pathophysiological relationship between hypertension and altered glucose metabolism during ingestion of a high‐sodium diet (8% NaCl, HSD). We tested the hypothesis that these two consequences of interrupted γ‐MSH signalling were the result of sympathetic activation by studying rats treated with the dopaminergic agonist bromocriptine (5 mg kg −1 i.p., daily for 1 week; Bromo) to cause relative γ‐MSH deficiency. Bromo‐treated rats fed the HSD developed hypertension and also exhibited fasting hyperglycaemia ( P < 0.005) and hyperinsulinaemia ( P < 0.025). Furthermore, Bromo‐treated rats on the HSD had impaired glucose tolerance and blunted insulin‐mediated glucose disposal. Intravenous infusion of γ 2 ‐MSH, or of the α‐adrenergic receptor antagonist phentolamine, to Bromo–HSD rats lowered both mean arterial pressure (MAP) and blood glucose to normal after 15 min ( P < 0.001 versus control), but had no effect in rats receiving vehicle and fed the HSD; γ 2 ‐MSH infusion also reduced the elevated plasma noradrenaline to control levels in parallel with the reductions in MAP and blood glucose concentration. Infusion of hydralazine to Bromo–HSD rats lowered MAP but had only a trivial effect on blood glucose. We conclude that rats with relative γ‐MSH deficiency develop abnormal glucose metabolism, with features of insulin resistance, in association with hypertension when ingesting the HSD. Elevated plasma noradrenaline concentration in Bromo–HSD rats is normalized by γ 2 ‐MSH infusion, suggesting that an adrenergic mechanism may link the salt‐sensitive hypertension and the impaired glucose metabolism of relative γ‐MSH deficiency.