Abstract
Renal autoregulation consists of two main mechanisms; the myogenic response and the tubuloglomerular feedback mechanism (TGF). Increases in renal perfusion pressure activate both mechanisms causing a reduction in diameter of the afferent arteriole (AA) resulting in stabilization of the glomerular pressure. It has previously been shown that connexin-40 (Cx40) is essential in the renal autoregulation and mediates the TGF mechanism. The aim of this study was to characterize the myogenic properties of the AA in wild-type and connexin-40 knockout (Cx40KO) mice using both in situ diameter measurements and modeling. We hypothesized that absence of Cx40 would not per se affect myogenic properties as Cx40 is expressed primarily in the endothelium and as the myogenic response is known to be present also in isolated, endothelium-denuded vessels. Methods used were the isolated perfused juxtamedullary nephron preparation to allow diameter measurements of the AA. A simple mathematical model of the myogenic response based on experimental parameters was implemented. Our findings show that the myogenic response is completely preserved in the AA of the Cx40KO and if anything, the stress sensitivity of the smooth muscle cell in the vascular wall is increased rather than reduced as compared to the WT. These findings are compatible with the view of the myogenic response being primarily a local response to the local transmural pressure.
Highlights
Renal autoregulation aims at maintaining a near constant renal blood flow (RBF) and glomerular filtration rate (GFR) during acute changes in renal perfusion pressure (RPP) (Shipley and Study 1951)
Our findings show that the myogenic response is completely preserved in the afferent arteriole (AA) of the connexin-40 knockout (Cx40KO) and, if anything, the stress sensitivity of the wall smooth muscle cell is increased rather than reduced as compared to the WT
The results show that as opposed to the tubuloglomerular feedback mechanism (TGF) the myogenic response measured in the AA is not dependent on expression of Cx40
Summary
Renal autoregulation aims at maintaining a near constant renal blood flow (RBF) and glomerular filtration rate (GFR) during acute changes in renal perfusion pressure (RPP) (Shipley and Study 1951). Myogenic tone depends on transmural pressure exposing the wall smooth muscle cell to a certain circumferential stress. The latter is likely the variable sensed by the wall (Davis and Hill 1999; Carlson and Secomb 2005). An increase in pressure causes a parallel increase in the stress which in turn is partially offset by myogenic contraction that reduces radius and increases wall thickness.
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