The renal vascular tree displays a highly irregular branching pattern such that the pre-glomerular resistance may differ markedly between two adjacent glomeruli. In spite of this, the filtration pressure is remarkably similar in different glomeruli.

Each organ has specific requirements for the vascular tree perfusing it. The kidney receives app. 1L of blood per min (1/5 of cardiac output) and filters 180L of plasma every day. This requires a high filtration pressure and a tight regulation of flow and pressure. In the kidneys, this control is driven in part by the ability of the vascular cells to communicate through gap junction. The structure of the renal vascular wall and the renal vascular tree are uniquely suited for this. The challenge in research is to generate a full 3D structure of the renal vascular tree in vivo. We will accomplish this using super-resolution imaging (SRI). Ultrasound scans of kidneys perfused with micro-bubbles will reveal the unique structure of the renal vascular tree in vivo. With this technique, we aim to estimating flow and pressure within the renal vasculature. Comparing kidneys from healthy and diseased (hypertensive, diabetic) animals will answer many questions regarding development of renal diseases.

A further advancement is the use of red blood cells as tracking target (substituting microbubbles) to convert super-resolution ultrasound into a non-invasive method. This high-gain high-risk project is funded by a Synergy Grant from the European Research Council (ERC).

The projects are a collaboration between the Sørensen group and researchers at DTU and Rigshospitalet.

Renal effects of GLP-1 and glucagon

The gut hormone GLP-1 also has renal effects. It increases renal blood flow, glomerular filtration rate and sodium excretion. We have shown that GLP-1 receptors are expressed in renal vascular smooth muscle cells but expression is significantly reduced in hypertensive animals. GLP-1 also attenuates renal autoregulation. This implicates GLP-1 as a major contributor in the control of renal hemodynamics. Furthermore, GLP-1 agonists has been shown to protect kidney function in patients with renal failure.

Glucagon increases renal excretion of sodium and potassium. It is known, that plasma levels of glucagon are high in people with type-2 diabetes. We are investigating the potential damaging effects of high plasma levels of glucagon on kidney function and a possible role in development of renal failure.

Ongoing GLP-1 projects

GLP-1 and sympathetic activity

Interactions between the sympathetic nervous system and GLP-1 in in the control of renal hemodynamics. Investigations in whole animals to assess the effect of GLP-1 on renal autoregulation and sodium excretion.

GLP-1 receptors in human kidneys

We are exploring GLP-1 receptor expression this using human renal tissue from healthy, diabetic and hypertensive patients to examine the location and possible changes in expression during diseases. Collaboration with SDU.

GLP-1 in renal vascular responses

GLP-1 induces renal vasodilation but the pathway is unclear. In isolated renal vessels we examine changes in intracellular Ca²⁺ and the effect of different ion channels inhibitors and activators.

Gap junctions allow signals to travel between cells. In the renal vasculature, gap junctions are found between vascular smooth muscle cells, between endothelial cells and between vascular smooth muscle cells - endothelial cells. Stimulation in one part of an arteriole leads to a response at a distant site. We have shown that this signal conduction participates in renal autoregulation. Also, the control of the renin-angiotensin system depends on functional gap junctions. This implicates gap junctions as a major contributor in the control of renal hemodynamics.

The myogenic response and the tubuloglomerular feedback (TGF) autoregulate renal blood flow and glomerular filtration rate. This depends on a functional communication between the vascular cells. Renal gap junctions are built from different connexin (Cx) isoforms: Cx37, Cx40, Cx43 and Cx45. The function and expression of Cx is changed during hypertension and diabetes.

Ongoing gap junction projects

In cooperation with Associate Professor Jens Christian Brings Jacobsen these experimental data is used to generate mathematical models of the renal autoregulation in order to elucidate the changes occurring in the vascular wall when intercellular communication is reduced.

In collaboration with Associate Professor Olga Sosnovtseva we investigate the changes in TGF induced by different gap junction upcouplers. We also investigate how changes in tubular flow (induced e.g. by SGLT2 inhibitors) affect renal autoregulation.

Ion channels in the renal re­sis­tan­ce vessels affect the cell membrane potential. This leads to changed permeability of voltage sensitive Ca²⁺ channels and vascular tone. We have shown that in diet induced and genetically induced hypertension the expression and function of vascular K⁺ channels is changed. This implicates K⁺ channels as a major contributor in the control of renal hemodynamics.

Ongoing ion channel projects

The vasodilatory effects of GLP-1 and glucagon may be regulated through K⁺ channels. This is explored in isolated renal arteries and in whole animals.