scholarly journals Differential effects of superoxide and hydrogen peroxide on myogenic signaling, membrane potential, and contractions of mouse renal afferent arterioles

2016 ◽  
Vol 310 (11) ◽  
pp. F1197-F1205 ◽  
Author(s):  
Lingli Li ◽  
En Yin Lai ◽  
Anton Wellstein ◽  
William J. Welch ◽  
Christopher S. Wilcox
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Perfusion Pressure ◽  
Principal Component ◽  
Muscle Cells ◽  
Luminal Diameter ◽  
Afferent Arterioles

Myogenic contraction is the principal component of renal autoregulation that protects the kidney from hypertensive barotrauma. Contractions are initiated by a rise in perfusion pressure that signals a reduction in membrane potential ( Em) of vascular smooth muscle cells to activate voltage-operated Ca2+ channels. Since ROS have variable effects on myogenic tone, we investigated the hypothesis that superoxide (O2·−) and H2O2 differentially impact myogenic contractions. The myogenic contractions of mouse isolated and perfused single afferent arterioles were assessed from changes in luminal diameter with increasing perfusion pressure (40–80 mmHg). O2·−, H2O2, and Em were assessed by fluorescence microscopy during incubation with paraquat to increase O2·− or with H2O2. Paraquat enhanced O2·− generation and myogenic contractions (−42 ± 4% vs. −19 ± 4%, P < 0.005) that were blocked by SOD but not by catalase and signaled via PKC. In contrast, H2O2 inhibited the effects of paraquat and reduced myogenic contractions (−10 ± 1% vs. −19 ± 2%, P < 0.005) and signaled via PKG. O2·− activated Ca2+-activated Cl− channels that reduced Em, whereas H2O2 activated Ca2+-activated and voltage-gated K+ channels that increased Em. Blockade of voltage-operated Ca2+ channels prevented the enhanced myogenic contractions with paraquat without preventing the reduction in Em. Myogenic contractions were independent of the endothelium and largely independent of nitric oxide. We conclude that O2·− and H2O2 activate different signaling pathways in vascular smooth muscle cells linked to discreet membrane channels with opposite effects on Em and voltage-operated Ca2+ channels and therefore have opposite effects on myogenic contractions.

scholarly journals TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential‐dependent coupling with PTEN

2019 ◽  
Vol 33 (9) ◽  
pp. 9785-9796 ◽  
Author(s):  
Takuro Numaga‐Tomita ◽  
Tsukasa Shimauchi ◽  
Sayaka Oda ◽  
Tomohiro Tanaka ◽  
Kazuhiro Nishiyama ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Plasma Membrane ◽  
Membrane Potential ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Phenotypic Switching ◽  
Plasma Membrane Potential

Abstract 34: Diminished Contractile Capability In Cerebral Vascular Smooth Muscle Cells In The TgF344-AD Rat Model Of Alzheimer's Disease

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Xing Fang ◽  
Huawei Zhang ◽  
Yedan Liu ◽  
Shaoxun Wang ◽  
Baoying Zheng ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Rat Model ◽  
Perfusion Pressure ◽  
Vascular Dysfunction ◽  
Muscle Cells ◽  
Model Of Alzheimer’S Disease ◽  
Cerebral Vascular

We recently reported that cerebral vascular dysfunction leads to impaired autoregulation of cerebral blood flow (CBF), neurovascular coupling (NVC), and blood-brain barrier (BBB) leakage. The present study examined if cerebral vascular dysfunction precedes cognitive impairment in the TgF344-AD (AD) rat model of Alzheimer's disease. In the present study, we confirmed that the AD rats develop learning and memory deficits beginning at 24-week of age using an eight-arm water maze. AD rats (n = 11) took a longer time to escape and displayed more errors than age-matched wildtype (WT) rats (n = 6). We also completed a longitudinal comparison of the myogenic response (MR) of the middle cerebral artery (MCA) and found that the MR was similar in AD and WT rats at 8- to 12-week of age when perfusion pressure was increased from 40 to 180 mmHg. However, the MR was significantly reduced in 16-week old AD rats (n = 6) as the inner diameter of the MCA only decreased by 8.2 ± 2.4% when perfusion pressure was increased from 40 to 180 mmHg compared with 14.5% ± 2.0% in age-matched WT rats (n = 6). The impaired MR of the MCA was exacerbated in AD rats with aging. Autoregulation of CBF AD rats (n = 4) in vivo was impaired in the surface and deep cortex at 24-week of age compared to age-matched WT rats (n = 4). Furthermore, we found the contractile capability of the cerebral vascular smooth muscle cells (VSMCs) isolated from AD rats (n = 4) was significantly reduced compared with WT rats (n = 4), detected by the reduction in size of 15.7 ± 0.9% vs. 25.4 ± 1.0% using a collagen gel-based assay kit. These results provide evidence that cerebral VSMC dysfunction, impaired MR, and autoregulation of CBF precede the development of memory and learning deficits in the TgF344-AD rat model. However, the underlying mechanisms for the loss of VSMCs contractility in this AD model overexpressing mutant human amyloid precursor protein ( APPsw ) and presenilin 1 ( PS1ΔE9 ) genes remain to be determined. Nevertheless, these results provide novel insight into the vascular contribution to AD.

Electrical membrane events in response to α-adrenoceptor stimulation

1985 ◽  
Vol 68 (s10) ◽  
pp. 51s-53s ◽  
Author(s):  
G. Haeusler ◽  
J. E. De Peyer
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Main Pulmonary Artery ◽  
Muscle Cells ◽  
Tension Development ◽  
Α2 Adrenoceptors ◽  
St 587

1. Strips of rabbit main pulmonary artery (RMPA) were used to study the effects of several agonists on tension development and membrane potential of the vascular smooth muscle cells. 2. The following α-adrenoceptor agonists were employed: methoxamine and St 587 (α1-selective), B-HT 920 (α2-selective) and clonidine, which stimulates preferentially α2-adrenoceptors. By the use of the selective antagonists prazosin and yohimbine it was not possible to differentiate convincingly between α1- and α2-adrenoceptors in the RMPA. Methoxamine and B-HT 920 produced depolarization of similar magnitude of the membrane of the vascular smooth muscle cells. In spite of these results, which point to a uniform α-adrenoceptor in the RMPA, contractions to α1-and α2-agonists differed in some important aspects. 3. Contractions in response to α2-agonists were highly susceptible to the inhibitory effects of calcium withdrawal and calcium antagonists whereas contractions to α1-agonists were much less so. Reduction of the membrane potential of the vascular cells by K+ at 12 mmol/l had no effect on the concentration-contraction curve of methoxamine but shifted that of B-HT 920 to the left. Conversely hyperpolarization of the membrane of the vascular smooth muscle cells by strychnine totally suppressed contraction to B-HT 920 and caused only a rightward shift of the concentration-contraction curve of methoxamine and St 587. 4. Interaction of α1- and α2-agonists with an apparently uniform α-adrenoceptor induces in the RMPA contraction which seems to be triggered by different membrane processes.

Effect of calcitonin, hydrocortisone, and parathyroid hormone on canine bone blood vessels

1981 ◽  
Vol 241 (1) ◽  
pp. H91-H94 ◽  
Author(s):  
M. Driessens ◽  
P. M. Vanhoutte
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Blood Vessels ◽  
Vascular Smooth Muscle Cells ◽  
Perfusion Pressure ◽  
Muscle Cells ◽  
Ringer Solution ◽  
Dependent Inhibition ◽  
Dose Dependent

Experiments were designed to determine whether or not calcitonin, parathormone, and glucocorticoids have direct effects on the vascular smooth muscle cells of bone blood vessels. Tibias of mongrel dogs were isolated. The arteria nutriens was cannulated and perfused at constant flow with aerated Krebs-Ringer solution (37 degrees C). The perfusion pressure was continuously recorded. In unstimulated preparations calcitonin caused dose-dependent increases in perfusion pressure, indicating that it causes constriction of bone blood vessels. Parathormone did not affect basal perfusion; it did not significantly alter vasoconstrictions caused by the injection of norepinephrine indicating that the hormone has no direct effect on the vascular smooth muscle of bone blood vessels. Hydrocortisone, at low concentrations, augmented the constrictions caused by exogenous norepinephrine and periarterial nerve stimulation; at higher concentrations, hydrocortisone caused a dose-dependent inhibition of the response to adrenergic activation. The depressant effect of hydrocortisone was antagonized by propranolol, suggesting that the glucocorticoid facilitates beta-adrenergic relaxation of the vascular smooth muscle cells by catecholamines.

Integrin-mediated mechanotransduction in renal vascular smooth muscle cells: activation of calcium sparks

2007 ◽  
Vol 293 (4) ◽  
pp. R1586-R1594 ◽  
Author(s):  
Lavanya Balasubramanian ◽  
Abu Ahmed ◽  
Chun-Min Lo ◽  
James S. K. Sham ◽  
Kay-Pong Yip
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Mechanical Force ◽  
Binding Peptide ◽  
Intracellular Ca ◽  
Afferent Arterioles ◽  
Paramagnetic Beads

Integrins are transmembrane heterodimeric proteins that link extracellular matrix (ECM) to cytoskeleton and have been shown to function as mechanotransducers in nonmuscle cells. Synthetic integrin-binding peptide triggers Ca2+ mobilization and contraction in vascular smooth muscle cells (VSMCs) of rat afferent arteriole, indicating that interactions between the ECM and integrins modulate vascular tone. To examine whether integrins transduce extracellular mechanical stress into intracellular Ca2+ signaling events in VSMCs, unidirectional mechanical force was applied to freshly isolated renal VSMCs through paramagnetic beads coated with fibronectin (natural ligand of α5β1-integrin in VSMCs). Pulling of fibronectin-coated beads with an electromagnet triggered Ca2+ sparks, followed by global Ca2+ mobilization. Paramagnetic beads coated with low-density lipoprotein, whose receptors are not linked to cytoskeleton, were minimally effective in triggering Ca2+ sparks and global Ca2+ mobilization. Preincubation with ryanodine, cytochalasin-D, or colchicine substantially reduced the occurrence of Ca2+ sparks triggered by fibronectin-coated beads. Binding of VSMCs with antibodies specific to the extracellular domains of α5- and β1-integrins triggered Ca2+ sparks simulating the effects of fibronectin-coated beads. Preincubation of microperfused afferent arterioles with ryanodine or integrin-specific binding peptide inhibited pressure-induced myogenic constriction. In conclusion, integrins transduce mechanical force into intracellular Ca2+ signaling events in renal VSMCs. Integrin-mediated mechanotransduction is probably involved in myogenic response of afferent arterioles.

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