Glucagon-like peptide (GLP)-1 has a range of extrapancreatic effects, including renal effects. The mechanisms are poorly understood, but GLP-1 receptors have been identified in the kidney. However, the exact cellular localization of the renal receptors is poorly described. The aim of the present study was to localize renal GLP-1 receptors and describe GLP-1-mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and that activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using ¹²⁵I-labeled GLP-1, ¹²⁵I-labeled exendin-4 (GLP-1 analog), and ¹²⁵I-labeled exendin 9–39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1-mediated effects on blood pressure, renal blood flow (RBF), heart rate, renin secretion, urinary flow rate, and Na⁺ and K⁺ excretion were investigated in anesthetized rats. Effects of GLP-1 on afferent arterioles were investigated in isolated mouse kidneys. Specific binding of ¹²⁵I-labeled GLP-1, ¹²⁵I-labeled exendin-4, and ¹²⁵I-labeled exendin 9–39 was observed in the renal vasculature, including afferent arterioles. Infusion of GLP-1 increased blood pressure, RBF, and urinary flow rate significantly in rats. Heart rate and plasma renin concentrations were unchanged. Exendin 9–39 inhibited the increase in RBF. In isolated murine kidneys, GLP-1 and exendin-4 significantly reduced the autoregulatory response of afferent arterioles in response to stepwise increases in pressure. We conclude that GLP-1 receptors are located in the renal vasculature, including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases RBF in normotensive rats.

Connexins (Cxs) are widely-expressed proteins that form gap junctions in most organs, including the kidney. In the renal vasculature, Cx37, Cx40, Cx43, and Cx45 are expressed, with predominant expression of Cx40 in the endothelial cells and Cx45 in the vascular smooth muscle cells. In the tubules, there is morphological evidence for the presence of gap junction plaques only in the proximal tubules. In the distal nephron, Cx30, Cx30.3, and Cx37 are expressed, but it is not known whether they form gap junctions connecting neighboring cells or whether they primarily act as hemichannels. As in other systems, the major function of Cxs in the kidney appears to be intercellular communication, although they may also form hemichannels that allow cellular secretion of large signaling molecules. Renal Cxs facilitate vascular conduction, juxtaglomerular apparatus calcium signaling, and tubular purinergic signaling. Accordingly, current evidence points to roles for these Cxs in several important regulatory mechanisms in the kidney, including the renin angiotensin system, tubuloglomerular feedback, and salt and water reabsorption. At the systemic level, renal Cxs may help regulate blood pressure and may be involved in hypertension and diabetes.

Row–column (RC) arrays have the potential to yield full 3-D ultrasound imaging with a greatly reduced number of elements compared to fully populated arrays. They, however, have several challenges due to their special geometry. This review article summarizes the current literature for RC imaging and demonstrates that full anatomic and functional imaging can attain a high quality using synthetic aperture (SA) sequences and modified delay-and-sum beamforming. Resolution can approach the diffraction limit with an isotropic resolution of half a wavelength with low sidelobe levels, and the field of view can be expanded by using convex or lensed RC probes. GPU beamforming allows for three orthogonal planes to be beamformed at 30 Hz, providing near real-time imaging ideal for positioning the probe and improving the operator’s workflow. Functional imaging is also attainable using transverse oscillation and dedicated SA sequence for tensor velocity imaging for revealing the full 3-D velocity vector as a function of spatial position and time for both blood velocity and tissue motion estimation. Using RC arrays with commercial contrast agents can reveal super-resolution imaging (SRI) with isotropic resolution below $20~ \mu \text{m}$ . RC arrays can, thus, yield full 3-D imaging at high resolution, contrast, and volumetric rates for both anatomic and functional imaging with the same number of receive channels as current commercial 1-D arrays.

Glucagon-like peptide-1 (GLP-1) and strategies based on this blood sugar-reducing and appetite-suppressing hormone are used to treat obesity and type 2 diabetes. However, the GLP-1 receptor (GLP-1R) is also present in the kidney, where it influences renal function. The effect of GLP-1 on the kidney varies between humans and rodents. The effect of GLP-1 on kidney function also seems to vary depending on its concentration and the physiological or pathological state of the kidney. In studies with rodents or humans, acute infusion of pharmacological doses of GLP-1 stimulates natriuresis and diuresis. However, the effect on the renal vasculature is less clear. In rodents, GLP-1 infusion increases renal plasma flow and glomerular filtration rate, suggesting renal vasodilation. In humans, only a subset of the study participants exhibits increased renal plasma flow and glomerular filtration rate. Differential status of kidney function and changes in renal vascular resistance of the preglomerular arterioles may account for the different responses of the human study participants. Because renal function in patients with type 2 diabetes is already at risk or compromised, understanding the effects of GLP-1R activation on kidney function in these patients is particularly important. This review examines the distribution of GLP-1R in the kidney and the effects elicited by GLP-1 or GLP-1R agonists. By integrating results from acute and chronic studies in healthy individuals and patients with type 2 diabetes along with those from rodent studies, we provide insight into how GLP-1R activation affects renal function and autoregulation.

Tubuloglomerular feedback (TGF) has an important role in autoregulation of renal blood flow and glomerular filtration rate (GFR). Because of the characteristics of signal transmission in the feedback loop, the TGF undergoes self-sustained oscillations in single-nephron blood flow, GFR, and tubular pressure and flow. Nephrons interact by exchanging electrical signals conducted electrotonically through cells of the vascular wall, leading to synchronization of the TGF-mediated oscillations. Experimental studies of these interactions have been limited to observations on two or at most three nephrons simultaneously. The interacting nephron fields are likely to be more extensive. We have turned to laser speckle contrast imaging to measure the blood flow dynamics of 50–100 nephrons simultaneously on the renal surface of anesthetized rats. We report the application of this method and describe analytic techniques for extracting the desired data and for examining them for evidence of nephron synchronization. Synchronized TGF oscillations were detected in pairs or triplets of nephrons. The amplitude and the frequency of the oscillations changed with time, as did the patterns of synchronization. Synchronization may take place among nephrons not immediately adjacent on the surface of the kidney.

Purpose We have previously demonstrated that glucagon-like peptide (GLP)-1, does not affect renal hemodynamics or function under baseline conditions in healthy individuals and in patients with type 2 diabetes mellitus. However, it is possible that GLP-1 promotes natriuresis under conditions with addition of salt and water to the extracellular fluid. The present study was designed to investigate a possible GLP-1-renal axis, inducing natriuresis in healthy, volume loaded individuals. Methods Under fixed sodium intake, 8 healthy men were examined twice in random order during a 3-hour infusion of either GLP-1(1.5 pmol kg^-1 min^-1) or vehicle together with an intravenous infusion of 0.9% NaCl. Timed urine collections were conducted throughout the experiments. Renal plasma flow (RPF), glomerular filtration rate (GFR), and uptake/release of hormones and ions were measured using Fick’s Principle. Results During GLP-1 infusion, urinary sodium and osmolar excretions increased significantly compared to vehicle. Plasma renin levels decreased similarly on both days, whereas angiotensin II (ANG II) levels decreased significantly only during GLP-1 infusion. RPF and GFR remained unchanged on both days. Conclusions In volume loaded subjects, GLP-1 induces significant natriuresis, likely brought about via a tubular mechanism secondary to suppression of ANG II, independent of renal hemodynamics, supporting the existence of a GLP-1-renal axis.