Metalloproteinases in plasma of the spontaneously hypertensive rats cleave the extracellular domain of beta 2‐adrenergic receptor.

Abstract

We recently observed enhanced metalloproteinase (MMP) activity in spontaneously hypertensive rats (SHR) compared to its normotensive Wistar Kyoto (WKY) rats and lyses of membrane receptors in the SHR by MMPs. The beta2‐adrenergic receptor (B2AR) is susceptible to the action of endogenous MMPs (Biochim Biophys Acta, 802:390, 1984). Thus we hypothesize that MMPs in plasma of SHR are able to lyse B2AR. Aorta of control Wistar rats was exposed for 24h (37°C) to fresh plasma of male Wistar and WKY rats and SHR with and without doxycycline (Doxy 30 μM) or EDTA (10 mM), to reduce MMP activity. The density of extracellular and intracellular domains of B2AR was determined by quantitative immunohistochemistry. The density of the extracellular, but not intracellular, domains of B2AR is reduced in aortic endothelial cells of the SHR compared with WKY or Wistar rats. Treatment of the aorta from Wistars with plasma from SHR, but not from WKY rats, reduced the number of extracellular domain, but not intracellular domain, of B2AR in aortic endothelial cells. Both Doxy and EDTA are able to prevent the cleavage of the extracellular domain. MMPs in plasma of SHR, but not WKY rats, cause cleavage of the extracellular domain of B2AR in endothelial cells of the aorta of Wistars. Thus MMPs may be responsible for the reduced density of the extracellular domain of B2AR in aortic endothelial cells of SHR compared to WKY rats.