To our knowledge, this is the first study investigating the cardiac structural and functional effects of in vivo activation of the novel receptor GPER in the female mRen2.Lewis rat, a congenic rodent model of salt-sensitive hypertension and early diastolic dysfunction [17] [19].
The inbred Dahl/Rapp rat is a genetic model of salt-sensitive hypertension [ 3, 4].
Therefore, in the present study, 8% NaCl diet was used to make a model of salt-sensitive hypertension.
To address this issue, in this work, we used DS rats which are a useful model of salt-sensitive hypertension and display insulin resistance and no fasting hyperglycemia [ 36- 39].
Finally, using a model of salt-sensitive hypertensive Dahl/Rapp rats, the levosimendan metabolite OR-1896 prevented salt-induced cardiovascular mortality and ameliorated cardiac hypertrophy and function, but without providing any significant renal protection [ 24].
The Dahl salt-sensitive (DS) rat is the most widely studied genetic model of salt-sensitive hypertension and was derived from Sprague Dawley rats by inbreeding based on their susceptibility or resistance to a high sodium chloride (HS) (7% NaCl) diet [ 56].
To test our hypothesis that DPP-4 inhibition can suppress cardiovascular injury induced by salt-sensitive hypertension, independently of glycemic control and blood pressure control, we examined the effect of linagliptin [ 22, 23], a DPP-4 inhibitor with unique xanthine-based structure, on cardiovascular injury in Dahl salt-sensitive hypertensive rats, a useful model of salt-sensitive hypertension.
Of direct relevance to the present discussion, A-438079, as well as a structurally distinct inhibitor of P2X7 receptors, Brilliant Blue G, were shown to reduce urinary albumin excretion, macrophage infiltration and BP in a rat model of salt-sensitive hypertension (Ji et al., 2012a).
