| Title | Evidence for a Noradrenergic Mechanism Causing Hypertension and Abnormal Glucose Metabolism in Rats with Relative Deficiency of {gamma}-Melanocyte Stimulating Hormone. | | Author(s) | Ni XP, Van Dijk C, Pearce D, Humphreys MH | | Institution | UCSF. | | Source | Exp Physiol 2009 May 8. | | Abstract | 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 gamma-melanocyte stimulating hormone (gamma-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 gamma-MSH signaling were the result of sympathetic activation by studying rats treated with the dopaminergic agonist bromocriptine (5 mg kg-1 ip qd x one week) (bromo) to cause relative gamma-MSH deficiency. Bromo-treated rats fed the HSD developed hypertension, and also exhibited fasting hyperglycemia (p<0.005) and hyperinsulinemia (p<0.025). Furthermore, bromo rats on the HSD had impaired glucose tolerance and blunted insulin-mediated glucose disposal. Intravenous infusion of gamma2-MSH, or of the alpha-adrenergic receptor antagonist phentolamine, to bromo-HSD rats lowered both MAP and blood glucose to normal after 15 min, (p<0.001 vs control), but had no effect in rats receiving vehicle and fed the HSD; gamma2-MSH infusion also reduced elevated plasma noradrenaline (NA) to control 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 gamma-MSH deficiency develop abnormal glucose metabolism, with features of insulin resistance, in association with hypertension when ingesting the HSD. Elevated plasma NA concentration in bromo-HSD rats is normalized with gamma2-MSH infusion, suggesting that an adrenergic mechanism may link the salt-sensitive hypertension and the impaired glucose metabolism of relative gamma-MSH deficiency. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19429645 |
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