Abstract

Oral administration of the peptide alamandine has antihypertensive and anti-fibrotic effects in rats. This work aimed to determine whether subcutaneous alamandine injection would attenuate hypertension and cardiac hypertrophy, and improve the function of a major target of hypertension-related damage, the left ventricle (LV), in spontaneously hypertensive rats (SHRs). This was examined in vivo in SHRs and normotensive rats subjected to 6-week subcutaneous infusion of alamandine or saline control, and in vitro in H9C2-derived and primary neonatal rat cardiomyocytes treated with angiotensin (Ang) II to model cardiac hypertrophy. Tail artery blood pressure measurement and transthoracic echocardiography showed that hypertension and impaired LV function in SHRs were ameliorated upon alamandine infusion. Alamandine administration also decreased the mass gains of heart and lung in SHRs, suppressed cardiomyocyte cross-sectional area expansion, and inhibited the mRNA levels of atrial natriuretic peptide and brain natriuretic peptide. The expression of alamandine receptor Mas-related G protein-coupled receptor, member D was increased in SHR hearts and in cardiomyocytes treated with Ang II. Alamandine inhibited the increases of protein kinase A (PKA) levels in the heart in SHRs and in cardiomyocytes treated with Ang II. In conclusion, the present study showed that alamandine administration attenuates hypertension, alleviates cardiac hypertrophy, and improves LV function. PKA signaling may be involved in the mechanisms underlying these effects.

Highlights

  • The left ventricle (LV) is one of the main targets of damage related to hypertension, which leads to LV structural changes and remodeling (Leung et al 2016), and eventually heart failure (Rizzello et al 2009)

  • Levels of the alamandine receptor MrgD were higher in the hearts of spontaneously hypertensive rats (SHRs) than of WKY rats (Fig. 4a), and Ang II treatment increased the expression of MrgD in primary cardiomyocytes (Fig. 4b)

  • protein kinase A (PKA) and p-Akt levels in the heart were higher in SHRs than in WKY rats, and alamandine administration reduced the increase in PKA, but not p-Akt, in the heart of SHRs (Fig. 5)

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Summary

Introduction

The left ventricle (LV) is one of the main targets of damage related to hypertension, which leads to LV structural changes and remodeling (Leung et al 2016), and eventually heart failure (Rizzello et al 2009). Specie Forward primer Reverse primer ANP Rat BNP GAPDH Rat

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