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I1-imidazoline receptor-mediated cardiovascular and metabolic effects in high-fat diet-induced metabolic syndrome in rats

Published:December 21, 2018DOI:https://doi.org/10.1016/j.autneu.2018.12.007

      Abstract

      Objectives

      The objective of this study was to investigate the effects of a new I1-imidazoline receptor-selective pyrroline compound on the hemodynamic, metabolic and microvascular alterations in a high-fat diet (HFD)-induced model of metabolic syndrome in rats.

      Methods

      In total, twenty adult male Wistar rats were fed a high-fat diet (HFD, n = 20) for 20 weeks. Thereafter, the rats received a new pyrroline compound selective for I1-imidazoline receptors (LNP599; 10 mg/kg/day) or vehicle (n = 10/group) orally by gavage for 4 weeks. Functional microcirculation was assessed using intravital video microscopy, and structural microcirculation was evaluated using histochemical analysis.

      Results

      LNP599 induced concomitant reductions in the SBP, HR and plasma catecholamine levels. The animals treated with this new antihypertensive compound also presented an improvement in body weight and the metabolic parameters related to metabolic syndrome, such as the glucose and lipid profiles. These effects were accompanied by a reversal of the functional and structural capillary rarefaction in the skeletal muscle.

      Conclusions

      The modulation of the sympathetic nervous system by a selective agonist for I1-imidazoline receptors improves the hemodynamic and metabolic parameters in an experimental model of metabolic syndrome. LNP599 can also contribute to the restoration of microcirculatory parameters.

      Abbreviations:

      A2R (α2-adrenergic receptor), FCD (functional capillary density), HFD (high-fat diet), HR (heart rate), I1R (I1-imidazoline receptor), MetS (metabolic syndrome), NEFAs (non-esterified fatty acids), RVLM (rostral ventrolateral medulla), SBP (systolic blood pressure), SCD (structural capillary density), SHR (spontaneously hypertensive rats), SNS (sympathetic nervous system)

      Keywords

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