The Credibility Effect and Rational Expectations: Implications of the Gramlich Study

macroeconomics, price shocks

Interpretation of a Regularity in the Behavior of M2

macroeconomics

Ryanodine receptor and capacitative Ca2+ entry in fresh preglomerular vascular smooth muscle cells

Ryanodine receptor and capacitative Ca2+ entry in fresh preglomerular vascular smooth muscle cells.BackgroundA multiplicity of hormonal, neural, and paracrine factors regulates preglomerular arterial tone by stimulating calcium entry or mobilization. We have previously provided evidence for capacitative (store-operated) Ca2+ entry in fresh renal vascular smooth muscle cells (VSMCs). Ryanodine-sensitive receptors (RyRs) have recently been identified in a variety of nonrenal vascular beds.MethodsWe isolated fresh rat preglomerular VSMCs with a magnetized microsphere/sieving technique; cytosolic Ca2+ ([Ca2+]i) was measured with fura-2 ratiometric fluorescence.ResultsRyanodine (3 μmol/L) increased [Ca2+]i from 79 to 138 nmol/L (P = 0.01). Nifedipine (Nif), given before or after ryanodine, was without effect. The addition of calcium (1 mmol/L) to VSMCs in calcium-free buffer did not alter resting [Ca2+]i. In Ca-free buffer containing Nif, [Ca2+]i rose from 61 to 88 nmol/L after the addition of the Ca2+-ATPase inhibitor cyclopiazonic acid and to 159 nmol/L after the addition of Ca2+ (1 mmol/L). Mn2+ quenched the Ca/fura signal, confirming divalent cation entry. In Ca-free buffer with Nif, [Ca2+]i increased from 80 to 94 nmol/L with the addition of ryanodine and further to 166 nmol/L after the addition of Ca2+ (1 mmol/L). Mn2+ quenching was again shown. Thus, emptying of the sarcoplasmic reticulum (SR) with ryanodine stimulated capacitative Ca2+ entry.ConclusionPreglomerular VSMCs have functional RyR, and a capacitative (store-operated) entry mechanism is activated by the depletion of SR Ca2+ with ryanodine, as is the case with inhibitors of SR Ca2+-ATPase

Endothelin A and B receptors of preglomerular vascular smooth muscle cells

BACKGROUND: The endothelin (ET) receptors are subclassified into ET(A,) which are purely vasoconstrictive, and ET(B). The ET(B) receptors may cause either vasodilation by stimulating the release of nitric oxide from endothelial cells, or vasoconstriction of vascular smooth muscle cells (VSMC). The relative contribution of ET(A) and ET(B) receptors to calcium signaling and vasoconstriction in the renal microcirculation is not clear. Our goal was to study the cytosolic calcium concentration ([Ca(2+)](i)) responses of fresh rat preglomerular VSMC and afferent arterioles to agonists and antagonists of ET(A) and ET(B) receptors in rats. METHODS: Fresh VSMC and afferent arterioles were isolated using the magnetized microsphere/sieving technique, followed by gentle collagenase digestion. [Ca(2+)](i) was measured with fura-2 ratiometric fluorescence. RESULTS: Afferent arterioles and VSMC responded to ET-1 stimulation with a rapid peak increase in [Ca(2+)](i) (Delta= 287 +/- 81 and 342 +/- 55 nmol/L, respectively). The ET(B) receptor agonist IRL 1620 stimulated a rise in [Ca(2+)](i) in afferent arterioles (106 +/- 35 nmol/L); subsequent addition of ET-1 at the IRL 1620 nadir to stimulate ET(A) receptors caused a second peak that was twice as large (213 +/- 44 nmol/L). In VSMC, the ET(B) agonist peak increase was 99 +/- 12 nmol/L; addition of ET-1 then increased [Ca(2+)](i) by 294 +/- 23 nmol/L. The ET(B) inhibitor BQ-788 prevented stimulation of [Ca(2+)](i) by IRL 1620 in afferent arterioles and VSMC; subsequent stimulation of ET(A) receptors with ET-1 caused an increase in [Ca(2+)](i) (239 +/- 17 and 248 +/- 22 nmol/L). Pretreatment with the selective ET(A) inhibitor PD 156707 attenuated but did not abolish the responses to ET-1, suggesting that the residual [Ca(2+)](i) response was caused by ET(B) stimulation. CONCLUSION: These results indicate that fresh preglomerular VSMC as well as afferent arterioles have both ET(A) and ET(B) receptors, and that the rapid peak [Ca(2+)](i) responses to the ET(B) agonist IRL 1620 are less than half that of subsequent stimulation of ET(A) receptors with ET-1. The similarity of findings in isolated VSMC and afferent arterioles suggests that responses in VSMC in our arteriolar preparation overshadow any potential contribution of endothelial cells when reagents are administered abluminally

Identification of BPIFA1/SPLUNC1 as an epithelium-derived smooth muscle relaxing factor

Asthma is a chronic airway disease characterized by inflammation, mucus hypersecretion and abnormal airway smooth muscle (ASM) contraction. Bacterial permeability family member A1, BPIFA1, is a secreted innate defence protein. Here we show that BPIFA1 levels are reduced in sputum samples from asthmatic patients and that BPIFA1 is secreted basolaterally from healthy, but not asthmatic human bronchial epithelial cultures (HBECs), where it suppresses ASM contractility by binding to and inhibiting the Ca2+ influx channel Orai1. We have localized this effect to a specific, C-terminal α-helical region of BPIFA1. Furthermore, tracheas from Bpifa1−/− mice are hypercontractile, and this phenotype is reversed by the addition of recombinant BPIFA1. Our data suggest that BPIFA1 deficiency in asthmatic airways promotes Orai1 hyperactivity, increased ASM contraction and airway hyperresponsiveness. Strategies that target Orai1 or the BPIFA1 deficiency in asthma may lead to novel therapies to treat this disease

Modern Economic Analysis

xiv; 459 hal.; ill.; 23 c

Modern economics analysis

xiv, 459 p.; 22 cm