scholarly journals Age‐dependent stretch‐induced myofilament calcium sensitization in ovine cerebral arteries

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Renan Joel Sandoval ◽  
William Julian Pearce
Keyword(s):  
Cerebral Arteries ◽  
Calcium Sensitization ◽  
Age Dependent

scholarly journals Myogenic contractility is more dependent on myofilament calcium sensitization in term fetal than adult ovine cerebral arteries

2007 ◽  
Vol 293 (1) ◽  
pp. H548-H556 ◽  
Author(s):  
Renan J. Sandoval ◽  
Elisha R. Injeti ◽  
James M. Williams ◽  
William T. Georthoffer ◽  
William J. Pearce
Keyword(s):  
Calcium Influx ◽  
Cerebral Arteries ◽  
Calcium Sensitivity ◽  
Cytosolic Calcium ◽  
Stretch Ratio ◽  
Myogenic Tone ◽  
Postnatal Maturation ◽  
Calcium Sensitization ◽  
Myofilament Calcium Sensitivity ◽  
Krebs Buffer

Regulation of cytosolic calcium and myofilament calcium sensitivity varies considerably with postnatal age in cerebral arteries. Because these mechanisms also govern myogenic tone, the present study used graded stretch to examine the hypothesis that myogenic tone is less dependent on calcium influx and more dependent on myofilament calcium sensitization in term fetal compared with adult cerebral arteries. Term fetal and adult posterior communicating cerebral arteries exhibited similar myogenic responses, with peak tensions averaging 24 and 26% of maximum contractile force produced in any given tissue in response to an isotonic Krebs buffer containing 122 mM K+ (Kmax) at optimum stretch ratios (working diameter/unstressed diameter) of 2.19 and 2.23, respectively. Graded stretch increased cytosolic Ca2+ concentration at stretch ratios >2.0 in adult arteries, but increased Ca2+ concentration only at stretch ratios >2.3 in fetal arteries. In permeabilized arteries, myogenic tone peaked at a stretch ratio of 2.1 in both fetal and adult arteries. The fetal %Kmax values at peak myogenic tone were not significantly different at either pCa 7.0 (23%) or pCa 5.5 (25%) but were significantly less at pCa 8.0 (8.4 ± 2.3%). Conversely, adult %Kmax values at peak myogenic tone were significantly less at both pCa 8.0 (10.4 ± 1.8%) and pCa 7.0 (16%) than at pCa 5.5 (27%). The maximal extents of stretch-induced increases in myosin light chain phosphorylation in intact fetal (20%) and adult (17%) arteries were similar. The data demonstrate that the cerebrovascular myogenic response is highly conserved during postnatal maturation but is mediated differently in fetal and adult cerebral arteries.

Age-Dependent Increase of Magnesium in the Cerebral Arteries of Thai

2006 ◽  
Vol 112 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Pasuk Mahakkanukrauh ◽  
Setsuko Tohno ◽  
Apichat Sinthubau ◽  
Yoshiyuki Tohno ◽  
Cho Azuma ◽  
...  
Keyword(s):  
Cerebral Arteries ◽  
Age Dependent

Selected Contribution: Effects of aging on cerebrovascular tone and [Ca2+]i

2003 ◽  
Vol 95 (4) ◽  
pp. 1746-1754 ◽  
Author(s):  
Greg G. Geary ◽  
John N. Buchholz
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Artery ◽  
Cerebral Arteries ◽  
No Synthase ◽  
The Other ◽  
Intraluminal Pressure ◽  
Age Dependent ◽  
Old Rats ◽  
Cerebral Blood Flow Autoregulation

The lower limits of cerebral blood flow autoregulation shift toward high pressures in aged compared with young rats. Intraluminal pressure stimulates contractile mechanisms in cerebral arteries that might, in part, cause an age-dependent shift in autoregulation. The present project tested two hypotheses. First, cerebral artery tone is greater in isolated arteries from aged compared with mature adult rats. Second, aging decreases the modulatory effect of endothelium-derived nitric oxide (NO) and increases vascular smooth muscle Ca2+ sensitivity. Isolated segments of middle cerebral arteries from male 6-, 12-, 20-, and 24-mo-old Fischer 344 rats were cannulated and loaded with fura-2. Diameter and Ca2+ responses to increasing pressure were measured in HEPES, during NO synthase inhibition [ NG-nitro-l-arginine methyl ester (l-NAME)], and after removal of the endothelium. Cerebral artery tone (with endothelium) increased with age. Only at the lowest pressure (20 and 40 mmHg) was intracellular Ca2+ concentration ([Ca2+]i) greater in arteries from 24-mo-old rats compared with the other age groups. l-NAME-sensitive constriction increased significantly in arteries from 6- to 20-mo-old rats but declined significantly thereafter in arteries from 24-mo-old rats. [Ca2+]i was less in arteries from 24-mo-old rats compared with the other groups after treatment with l-NAME. Another endothelial-derived factor, insensitive to l-NAME, also decreased significantly with age. For example, at 60 mmHg, the l-NAME-insensitive constriction decreased from 47 ± 10, 42 ± 5, 21 ± 2, and 3 ± 1 μm in 6-, 12-, 20-, and 24-mo-old rats, respectively. Our data suggest that aging alters cerebral artery tone and [Ca2+]i responses through endothelial-derived NO synthase-sensitive and -insensitive mechanisms. The combined effect of greater cerebral artery tone with less endothelium-dependent modulation may in part contribute to the age-dependent shift in cerebral blood flow autoregulation.

scholarly journals Gestational Age-Dependent Interplay between Endocannabinoid Receptors and Alcohol in Fetal Cerebral Arteries

2018 ◽  
Vol 08 (01) ◽  
Author(s):  
Maria Simakova ◽  
Ana Tobiasz ◽  
Ryan D Sullivan ◽  
Shivantika Bisen ◽  
Jose Duncan ◽  
...  
Keyword(s):  
Gestational Age ◽  
Cerebral Arteries ◽  
Age Dependent

Immunological reaction against the aging human subarachnoid erythrocyte

1989 ◽  
Vol 71 (5) ◽  
pp. 718-726 ◽  
Author(s):  
John W. Peterson ◽  
Byung-Duk Kwun ◽  
Atsushi Teramura ◽  
John D. Hackett ◽  
Jeffrey A. Morgan ◽  
...  
Keyword(s):  
Blood Clot ◽  
Cerebral Arteries ◽  
Cell Types ◽  
Complement Protein ◽  
Content Type ◽  
Artificial Cerebrospinal Fluid ◽  
Age Dependent ◽  
Subarachnoid Blood

✓ The role of the aging human erythrocyte in the mechanisms leading to cerebral vasospasm after subarachnoid hemorrhage was investigated using an in vitro model for the environment of the erythrocyte in a subarachnoid blood clot. It has long been suspected that, due to its potent vasoactivity, erythrocyte lysate provides the major vasoconstrictive input to cerebral arteries during vasospasm. Under the model conditions (incubation at 37°C in an artificial cerebrospinal fluid), however, the rate of spontaneous hemolysis was quite slow (about 1%/day), becoming only somewhat more rapid after 4 days' incubation. The rate of hemolysis of aging erythrocytes was dramatically increased (500- to 1000-fold) by the addition of plasma proteins, but only after the erythrocytes had aged 2 to 3 days, or more. The mechanism of age-dependent, plasma-induced hemolysis of originally autologous erythrocytes is shown to involve activation of the plasma complement protein pathway, analogous to the mechanisms of innate immunity which lead to lysis of nonautologous cell types and activate the inflammatory response.

Maturation depresses mouse cerebrovascular tone through endothelium-dependent mechanisms

2003 ◽  
Vol 284 (3) ◽  
pp. R734-R741 ◽  
Author(s):  
Greg G. Geary ◽  
John N. Buchholz ◽  
William J. Pearce
Keyword(s):  
Adult Mouse ◽  
Cerebral Arteries ◽  
Myogenic Tone ◽  
Intact Mouse ◽  
Vasoactive Factors ◽  
Important Interaction ◽  
Age Dependent ◽  
Oxide Synthase ◽  
Arterial Tone ◽  
Subsequent Addition

In light of previous observations that the range of arterial pressures over which cerebral blood flow is autoregulated differs dramatically in neonates and adults, the present experiments explored the hypothesis that pressure-induced intrinsic arterial tone is regulated differently in neonatal and adult cerebral arteries. In cannulated and pressurized endothelium-intact mouse cerebral arteries <150 μm in diameter, active intrinsic tone was evident at intraluminal pressures as low as 10 mmHg in neonatal arteries, but only at pressures of 60 mmHg or greater in adult arteries. Administration of 10 μM indomethacin produced no significant effect on tone at any pressure in either neonatal or adult arteries, but subsequent addition of 100 μM nitroarginine methyl ester (NAME) significantly vasoconstricted both neonatal and adult arteries at all pressures. Conversely, administration of 100 μM NAME alone significantly vasoconstricted adult arteries only, and subsequent addition of 10 μM indomethacin produced a significant additional vasoconstriction in adult arteries only, indicating an important interaction between the nitric oxide synthase and cyclooxygenase pathways, at least in adult arteries. In the presence of both indomethacin and NAME, intrinsic tone was significantly greater in neonatal than adult arteries, but when the endothelium was removed, tone was similar in neonatal and adult arteries at all pressures. Together, these results suggest that pressure-induced myogenic tone is regulated similarly in neonatal and adult mouse cerebral arteries but that the contribution of endothelial vasoactive factors to intrinsic tone is highly age dependent.

Relative contribution of Rho kinase and protein kinase C to myogenic tone in rat cerebral arteries in hypertension

2005 ◽  
Vol 289 (5) ◽  
pp. H1917-H1922 ◽  
Author(s):  
Yagna P. R. Jarajapu ◽  
Harm J. Knot
Keyword(s):  
Smooth Muscle ◽  
Arterial Wall ◽  
Kinase Inhibitors ◽  
Cerebral Arteries ◽  
Rho Kinase ◽  
Myogenic Tone ◽  
Calcium Sensitization ◽  
Wky Rats ◽  
Relative Contribution ◽  
Rho Kinase Inhibitors

Arterial smooth muscle constriction in response to pressure, i.e., myogenic tone, may involve calcium-dependent and calcium-sensitization mechanisms. Calcium sensitization in vascular smooth muscle is regulated by kinases such as PKC and Rho kinase, and activity of these kinases is known to be altered in cardiovascular disorders. In the present study, we evaluated the relative contribution of PKC and Rho kinase to myogenic tone in cerebral arteries in hypertension. Myogenic tone and arterial wall calcium in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were measured simultaneously, and the effect of PKC and Rho kinase inhibitors on myogenic tone was evaluated. SHR arteries showed significantly greater myogenic tone than WKY arteries. Pressure/wall tension-arterial wall calcium curves showed a hyperbolic relation in WKY rats, but the curves for SHR arteries were parabolic. Myogenic tone was decreased by the Rho kinase inhibitors Y-27632 and HA-1077, with a significantly greater effect in SHR than in WKY arteries. Reduction in myogenic tone produced by the PKC inhibitor bisindolylmaleimide I in WKY and SHR arteries was significantly less than that produced by Rho kinase inhibition. The pressure-dependent increase in myogenic tone was significantly decreased by Y-27632, and the decrease was markedly greater than that produced by bisindolylmaleimide I in SHR arteries. In WKY arteries, the pressure-dependent increase in myogenic tone was decreased to a similar extent by Y-27632 and bisindolylmaleimide I. These results suggest greater myogenic tone with increased calcium sensitization in SHR arteries, largely because of Rho kinase activation, with a minor contribution of PKC activation.

scholarly journals Pressure-dependent contribution of Rho kinase-mediated calcium sensitization in serotonin-evoked vasoconstriction of rat cerebral arteries

2010 ◽  
Vol 588 (10) ◽  
pp. 1747-1762 ◽  
Author(s):  
Ahmed F. El-Yazbi ◽  
Rosalyn P. Johnson ◽  
Emma J. Walsh ◽  
Kosuke Takeya ◽  
Michael P. Walsh ◽  
...  
Keyword(s):  
Cerebral Arteries ◽  
Rho Kinase ◽  
Calcium Sensitization

Age-dependent modulation of endothelium-dependent vasodilatation by chronic hypoxia in ovine cranial arteries

2006 ◽  
Vol 100 (1) ◽  
pp. 225-232 ◽  
Author(s):  
James M. Williams ◽  
William J. Pearce
Keyword(s):  
Smooth Muscle ◽  
Chronic Hypoxia ◽  
Cerebral Arteries ◽  
Volume Of Distribution ◽  
Small Contribution ◽  
Age Dependent ◽  
Nonpregnant Adult ◽  
And Function ◽  
Chronic Hypoxemia

Although abundant evidence indicates that chronic hypoxia can induce pulmonary vascular remodeling, very little is known of the effects of chronic hypoxia on cerebrovascular structure and function, particularly in the fetus. Thus the present study explored the hypothesis that chronic hypoxemia also influences the size and shape of cerebrovascular smooth muscle and endothelial cells, with parallel changes in the reactivity of these cells to endothelium-dependent vasodilator stimuli. To test this hypothesis, measurements of endothelial and vascular smooth muscle cell size and density were made in silver-stained common carotid and middle cerebral arteries from term fetal and nonpregnant adult sheep maintained at an altitude of 3,820 m for 110 days. Chronic hypoxia induced an age-dependent remodeling that led to smooth muscle cells that were larger in fetal arteries but smaller in adult arteries. Chronic hypoxia also increased endothelial cell density in fetal arteries but reduced it in adult arteries. These combined effects resulted in an increased (adult carotid), decreased (adult middle cerebral), or unchanged (fetal arteries) per cell serosal volume of distribution for endothelial factors. Despite this heterogeneity, the magnitude of endothelium-dependent vasodilatation to A23187 , measured in vitro, was largely preserved, although sensitivity to this relaxant was uniformly depressed. NG-nitro-l-arginine methyl ester, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, and endothelium denudation each independently blocked A23187 -induced vasodilation without unmasking any residual vasoconstrictor effect. Indomethacin did not significantly attenuate A23187 -induced relaxation except in the hypoxic adult middle cerebral, where a small contribution of prostanoids was evident. Vascular sensitivity to exogenous nitric oxide (NO) was uniformly increased by chronic hypoxia. From these results, we conclude that chronic hypoxia reduced endothelial NO release while also upregulating some component of the NO-cGMP-PKG vasodilator pathway. These offsetting effects appear to preserve endothelium-dependent vasodilation after adaptation to chronic hypoxia.

Developmental changes in alpha 1-adrenergic receptors, IP3 responses, and NE-induced contraction in cerebral arteries

1996 ◽  
Vol 271 (6) ◽  
pp. H2313-H2319 ◽  
Author(s):  
L. D. Longo ◽  
N. Ueno ◽  
Y. Zhao ◽  
W. J. Pearce ◽  
L. Zhang
Keyword(s):  
Cerebral Artery ◽  
Adrenergic Receptors ◽  
Cerebral Arteries ◽  
Developmental Changes ◽  
Developmental Age ◽  
Age Dependent ◽  
Density Values ◽  
The Common ◽  
Pharmacomechanical Coupling ◽  
Dose Dependent

Cerebral arteries show significant developmental and artery-specific changes in noradrenergic-mediated contraction. To test the hypothesis that these changes result from differences in the density of alpha 1-adrenergic receptors (alpha 1-ARs) and/or norepinephrine (NE)-induced inositol 1,4,5-trisphosphate [Ins(1,4,5)P3,IP3] synthesis, we quantified these variables and the NE-induced contraction in the common carotid artery (Com) and main branch cerebral arteries (MBC) from term fetal (approximately 140 gestational day) and newborn (2- to 5-day) sheep and compared them with adult values. In fetal and newborn Com, maximal contractions to NE (percent K+ maximum response) were 132 +/- 14 and 118 +/- 9%, respectively (adult = 92 +/- 7%). For fetal and newborn middle cerebral artery, these values were 34 +/- 10 and 43 +/- 7%, respectively (adult = 24 +/- 7%). alpha 1-AR density values in Com of fetal and newborn sheep were 113 +/- 18 and 106 +/- 4 fmol/mg protein, respectively (adult = 54 +/- 3 fmol/mg protein). For the MBC, density values were 47 +/- 2 and 24 +/- 3 fmol/mg protein, respectively (adult = 23 +/- 3 fmol/protein). In term fetal and newborn MBC, NE produced dose-dependent increases in Ins(1,4,5)P3, the maximal increases above basal values being 245 +/- 40 and 189 +/- 16%, respectively (adult = 254 +/- 35%). Neither fetus nor newborn Com showed significant Ins(1,4,5)P3 responses to NE. We concluded that in fetal and newborn Com and MBC, alpha 1-AR density and NE-induced Ins(1,4,5)P3 response varied as a function of developmental age and specific vessel. However, these variations did not correlate with NE-induced maximum contraction. Thus we reject the hypothesis that age-dependent and vessel-specific differences of cerebral artery adrenergic-mediated contraction are a function of alpha 1-AR density or Ins(1,4,5)P3 response. Rather, the differences would appear to result from other factors such as non-Ins(1,4,5)P3-mediated calcium activation and/or sensitivity to Ins(1,4,5)P3. The studies also suggest considerable potential for maturational modulation of pharmacomechanical coupling and homeostatic regulation of cerebrovascular tone.

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