Role of Substance P in Renal Injury during DOCA‐salt Hypertension

Abstract

To determine the role of substance P (SP) in salt‐sensitive hypertension‐induced renal damage, we induced hypertension by uninephrectomy and deoxycorticosterone (DOCA)‐salt in mice with or without selective NK1 antagonists. DOCA‐salt treatment for 5 weeks increased mean arterial pressure (MAP) (P<0.01) and urinary albumin excretion (P<0.05), and also induced renal hypertrophy (P<0.01) compared with the control. Periodic acid‐ Schiff and Masson's trichrome staining showed that DOCA‐salt treatment caused obvious glomerulosclrosis and tubulointerstitial injury in the renal cortex (P<0.05), and tubulointerstitial fibrosis compared with the control mice. Consistent with the results, renal collagen level determined using hydroxyproline assay was higher in DOCA‐salt‐treated mice compared with the control mice (P<0.05). Blockade of the NK1 receptor with RP‐67580 (8 mg/kg/day, ip) or L‐733,060 (20 mg/kg/day, ip) had no effect on MAP and renal hypertrophy. However, they partially prevented renal morphological damage and reduced the increase in urinary albumin excretion and renal collagen (P<0.05). Our data showed that blockade of NK1 receptors with RP‐67580 or L‐733,060 prevented renal damage induced by DOCA‐salt hypertension independently of their effects on blood pressure. The results suggest that activation of NK1 receptors by SP may contribute to renal damage during DOCA‐salt hypertension. This work was supported in part by the National Natural Science Foundation of China (No. 81170243).