Effects of centrally administered glucagon-like peptide-2 on blood pressure and barosensitive neurons in spontaneously hypertensive rats

The central administration of glucagon-like peptide-2 (GLP-2) decreases blood pressure in rats. In the present study, we investigated the hypotensive effects of GLP-2 using spontaneously hypertensive rats (SHRs), an animal model of hypertension. The central administration of GLP-2 (0.6 mu g) decreased mean arterial pressure (MAP) in SHRs (-24.1 +/- 4.5%; P < 0.05), but not in normotensive Wistar-Kyoto (WKY) rats (-10.6 +/- 7.4%; P > 0.05), whereas GLP-2 (6 mu g) decreased MAP in WKY rats (-23.5 +/- 4.2%; P < 0.05) and SHRs (-46.7 +/- 11.6%; P < 0.01) under anesthesia with urethane and a-chloralose. Histological analyses revealed that the central administration of GLP-2 (6 mu g) induced Fos immunoreactivity (Fos-IR) in the hypothalamic and medullary areas in WKY rats and SHRs. However, the distribution of Fos-IR in GABAergic neurons in the rostral ventrolateral medulla (RVLM) differed between WKY rats and SHRs. GLP-2 directly modulated the excitability of RVLM neurons in brainstem slices from SHRs, but not WKY rats. These results suggest that neuronal activity through the activation of GLP-2 receptors in the RVLM contributes to lowering blood pressure in SHRs.