Mechanism of vasoactive peptide intermedin in vascular collagen remodeling during angiotensin II-induced hypertention.

OBJECTIVE: Renin-angiotensin axis plays a pivotal role in the cardiovascular system, and Angiotensin II (Ang II) is of great importance in the progression of hypertension. Vasoactive peptide intermedin (IMD) belongs to calcitonin gene-related peptide (CGRP) family, which is involved in the regulation of the cardiovascular function. This study aims to determine the effect of vasoactive peptide intermedin on vascular collagen remodeling caused by angiotensin II-induced hypertension.

MATERIALS AND METHODS: 12-week old rats were randomly assigned into three groups, and each group consisted of 12 rats. Rats were administered with Ang II or Ang II+IMD, respectively. Control group received saline administration. Blood pressure of caudal artery was examined two weeks after administration. Serum procollagen I and III were detected by enzyme-linked immunosorbent assay (ELISA). The vascular microstructure was examined via hematoxylin-eosin (HE) staining to evaluate vascular collagen remodeling. Expressions of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) were tested by using Western-blot and RT-PCR.

RESULTS: Compared with the control group (92.2±9.1 mmHg), blood pressure of group Ang II was increased by 88% (173.1±11.2 mmHg) (p<0.01). Moreover, blood pressure level in group Ang II+IMD (131.0±10.9 mmHg) was reduced compared to that in group Ang II (p<0.05). Compared with that in control group, higher level of serum procollagen, with significantly increasing vascular W/C ratio and collagen area percentage, was found in group Ang II, while all testing indexes above in group Ang II+IMD were lower than that in group Ang II. No differences were detected in the levels of Akt and MAPK mRNA among all three groups. However, highest expressions of phosphorylation Akt and MAPK protein were shown in group Ang II, and the levels were gradually lower in groups of Ang II+IMD and control.

CONCLUSIONS: IMD could attenuate the vascular collagen remodeling caused by angiotensin II-induced hypertension via inhibiting phosphorylation of Akt and MAPK.