Adaptive responses of rat descending vasa recta to ischemia.

tested whether rat descending vasa recta (DVR) undergo regulatory adaptations after the kidney is exposed to ischemia. Left kidneys (LK) were subjected to 30-min renal artery cross clamp. After 48 h, the postischemic LK and contralateral right kidney (RK) were harvested for study.

High serum creatinine nonlinearity: a renal vital sign?

Patients with chronic kidney disease (CKD) may have nonlinear serum creatinine concentration (SC) trajectories, especially as CKD progresses. Variability in SC is associated with renal failure and death. However, present methods for measuring SC variability are unsatisfactory because they blend information about SC slope and variance.

Descending Vasa Recta Endothelial Membrane Potential Response Requires Pericyte Communication.

Using dual-cell electrophysiological recording, we examined the routes for equilibration of membrane potential between the pericytes and endothelia that comprise the descending vasa recta (DVR) wall. We measured equilibration between pericytes in intact vessels, between pericytes and endothelium in intact vessels and between pericytes physically separated from the endothelium. Dual pericyte recording on the abluminal surface of DVR showed that both resting potential and subsequent time-dependent voltage fluctuations after vasoconstrictor stimulation remained closely equilibrated, regardless of the agonist employed (angiotensin II, vasopressin or endothelin 1).

Syncytial communication in descending vasa recta includes myoendothelial coupling.

Using dual cell patch-clamp recording, we examined pericyte, endothelial, and myoendothelial cell-to-cell communication in descending vasa recta. Graded current injections into pericytes or endothelia yielded input resistances of 220 ± 21 and 128 ± 20 MΩ, respectively (P < 0.05).

Descending vasa recta endothelial cells and pericytes form mural syncytia.

Using patch clamp, we induced depolarization of descending vasa recta (DVR) pericytes or endothelia and tested whether it was conducted to distant cells. Membrane potential was measured with the fluorescent voltage dye di-8-ANEPPS or with a second patch-clamp electrode. Depolarization of an endothelial cell induced responses in other endothelia within a millisecond and was slowed by gap junction blockade with heptanol.

Mural propagation of descending vasa recta responses to mechanical stimulation.

To investigate the responses of descending vasa recta (DVR) to deformation of the abluminal surface, we devised an automated method that controls duration and frequency of stimulation by utilizing a stream of buffer from a micropipette. During stimulation at one end of the vessel, fluorescent responses from fluo4 or bis[1,3-dibutylbarbituric acid-(5)] trimethineoxonol [DiBAC₄(3)], indicating cytoplasmic calcium ([Ca²⁺]CYT) or membrane potential, respectively, were recorded from distant cells. Alternately, membrane potential was recorded from DVR pericytes by nystatin whole cell patch-clamp.

Effects of deoxycholylglycine, a conjugated secondary bile acid, on myogenic tone and agonist-induced contraction in rat resistance arteries.

Background: Bile acids (BAs) regulate cardiovascular function via diverse mechanisms. Although in both health and disease serum glycine-conjugated BAs are more abundant than taurine-conjugated BAs, their effects on myogenic tone (MT), a key determinant of systemic vascular resistance (SVR), have not been examined.

Methodology/principal Findings: Fourth-order mesenteric arteries (170-250 µm) isolated from Sprague-Dawley rats were pressurized at 70 mmHg and allowed to develop spontaneous constriction, i.

Renal medullary circulation.

The renal medullary microcirculation is a distinctive arrangement of blood vessels that serve multiple functions in the renal medulla. This article begins with a description of the unique anatomy of this vascular bed and the role it plays in transport and countercurrent exchange in the medulla. A segment of the review is then devoted to the important role mathematical modeling has played in the understanding of this vascular bed's function.

How NaCl raises blood pressure: a new paradigm for the pathogenesis of salt-dependent hypertension.

Excess dietary salt is a major cause of hypertension. Nevertheless, the specific mechanisms by which salt increases arterial constriction and peripheral vascular resistance, and thereby raises blood pressure (BP), are poorly understood. Here we summarize recent evidence that defines specific molecular links between Na(+) and the elevated vascular resistance that directly produces high BP.

Bile acids regulate cardiovascular function.

Research over the last decade has uncovered roles for bile acids (BAs) that extend beyond their traditional functions in regulating lipid digestion and cholesterol metabolism. BAs are now recognized as signaling molecules that interact with both plasma membrane and nuclear receptors. Emerging evidence indicates that by interacting with these receptors, BAs regulate their own synthesis, glucose and energy homeostasis, and other important physiological events.

Cellular mechanisms underlying nitric oxide-induced vasodilation of descending vasa recta.

It has been observed that vasoactivity of explanted descending vasa recta (DVR) is modulated by intrinsic nitric oxide (NO) and superoxide (O(2)(-)) production (Cao C, Edwards A, Sendeski M, Lee-Kwon W, Cui L, Cai CY, Patzak A, Pallone TL. Am J Physiol Renal Physiol 299: F1056-F1064, 2010). To elucidate the cellular mechanisms by which NO, O(2)(-) and hydrogen peroxide (H(2)O(2)) modulate DVR pericyte cytosolic Ca(2+) concentration ([Ca](cyt)) and vasoactivity, we expanded our mathematical model of Ca(2+) signaling in pericytes.

Intrinsic nitric oxide and superoxide production regulates descending vasa recta contraction.

Descending vasa recta (DVR) are 12- to 15-μm microvessels that supply the renal medulla with blood flow. We examined the ability of intrinsic nitric oxide (NO) and reactive oxygen species (ROS) generation to regulate their vasoactivity. Nitric oxide synthase (NOS) inhibition with N(ω)-nitro-l-arginine methyl ester (l-NAME; 100 μmol/l), or asymmetric N(G),N(G)-dimethyl-l-arginine (ADMA; 100 μmol/l), constricted isolated microperfused DVR by 48.

Murine vasa recta pericyte chloride conductance is controlled by calcium, depolarization, and kinase activity.

We used the whole cell patch-clamp technique to investigate the regulation of descending vasa recta (DVR) pericyte Ca(2+)-dependent Cl(-) currents (CaCC) by cytoplasmic Ca(2+) concentration ([Ca](CYT)), voltage, and kinase activity. Murine CaCC increased with voltage and electrode Ca(2+) concentration. The current saturated at [Ca](CYT) of ∼1,000 nM and exhibited an EC(50) for Ca(2+) of ∼500 nM, independent of depolarization potential.

Voltage-gated divalent currents in descending vasa recta pericytes.

Multiple voltage-gated Ca(2+) channel (Ca(V)) subtypes have been reported to participate in control of the juxtamedullary glomerular arterioles of the kidney. Using the patch-clamp technique, we examined whole cell Ca(V) currents of pericytes that contract descending vasa recta (DVR). The dihydropyridine Ca(V) agonist FPL64176 (FPL) stimulated inward Ca(2+) and Ba(2+) currents that activated with threshold depolarizations to -40 mV and maximized between -20 and -10 mV.

Sympathetic nerves and the endothelium influence the vasoconstrictor effect of low concentrations of ouabain in pressurized small arteries.

We hypothesized that in salt-dependent forms of hypertension, endogenous ouabain acts on arterial smooth muscle to cause enhanced vasoconstriction. Here, we tested for the involvement of the arterial endothelium and perivascular sympathetic nerve terminals in ouabain-induced vasoconstriction. Segments of rat mesenteric or renal interlobar arteries were pressurized to 70 mmHg at 37 degrees C and exposed to ouabain (10(-11)-10(-7) M).

Iodixanol, constriction of medullary descending vasa recta, and risk for contrast medium-induced nephropathy.

Purpose: To determine whether a type of contrast medium (CM), iodixanol, modifies outer medullary descending vasa recta (DVR) vasoreactivity and nitric oxide (NO) production in isolated microperfused DVR.

Materials And Methods: Animal handling conformed to the Animal Care Committee Guidelines of all participating institutions. Single specimens of DVR were isolated from rats and perfused with a buffered solution containing iodixanol.

Chronic ouabain treatment induces vasa recta endothelial dysfunction in the rat.

Descending vasa recta (DVR) are 15-microm vessels that perfuse the renal medulla. Ouabain has been shown to augment DVR endothelial cytoplasmic Ca(2+) ([Ca(2+)](CYT)) signaling. In this study, we examined the expression of the ouabain-sensitive Na-K-ATPase alpha2 subunit in the rat renal vasculature and tested effects of acute ouabain exposure and chronic ouabain treatment on DVR.

Mechanisms underlying angiotensin II-induced calcium oscillations.

To gain insight into the mechanisms that underlie angiotensin II (ANG II)-induced cytoplasmic Ca2+ concentration ([Ca]cyt) oscillations in medullary pericytes, we expanded a prior model of ion fluxes. ANG II stimulation was simulated by doubling maximal inositol trisphosphate (IP3) production and imposing a 90% blockade of K+ channels. We investigated two configurations, one in which ryanodine receptors (RyR) and IP3 receptors (IP3R) occupy a common store and a second in which they reside on separate stores.

Membrane current oscillations in descending vasa recta pericytes.

We investigated the origin of spontaneous transient inward current (STIC) oscillations in descending vasa recta (DVR) pericytes. In cells clamped at -80 mV, angiotensin II (ANG II; 10 nmol/l) induced oscillations with mean amplitude and frequency of -65.5 pA and 1.

Ouabain modulation of cellular calcium stores and signaling.

Ouabain-like factors modulate intracellular Ca2+ concentrations and Ca2+ stores. Recently, a role for Na+-K+-ATPase Na+ transport inhibition as a pivotal event in ouabain signaling was questioned (Kaunitz JD. Am J Physiol Renal Physiol 290: F995-F996, 2006).

Descending vasa recta endothelia express inward rectifier potassium channels.

Descending vasa recta (DVR) are capillary-sized microvessels that supply blood flow to the renal medulla. They are composed of contractile pericytes and endothelial cells. In this study, we used the whole cell patch-clamp method to determine whether inward rectifier potassium channels (K(IR)) exist in the endothelia, affect membrane potential, and modulate intracellular Ca(2+) concentration ([Ca(2+)](cyt)).