scholarly journals Estrogen reduces mouse cerebral artery tone through endothelial NOS- and cyclooxygenase-dependent mechanisms

2000 ◽  
Vol 279 (2) ◽  
pp. H511-H519 ◽  
Author(s):  
Greg G. Geary ◽  
Diana N. Krause ◽  
Sue P. Duckles
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
Cerebral Artery ◽  
Cerebral Arteries ◽  
Estrogen Replacement ◽  
Luminal Diameter ◽  
Small Resistance ◽  
Oxide Synthase

Gender and estrogen status are known to influence the incidence and severity of cerebrovascular disease. The vasoprotective effects of estrogen are thought to include both nitric oxide-dependent and independent mechanisms. Therefore, using small, resistance-sized arteries pressurized in vitro, the present study determined the effect of gender and estrogen status on myogenic reactivity of mouse cerebral arteries. Luminal diameter was measured in middle cerebral artery segments from males and from females that were either untreated, ovariectomized (OVX), or OVX with estrogen replacement (OVX + EST). The maximal passive diameters of arteries from all four groups were similar. In response to increases in transmural pressure, diameters of arteries from males and OVX females were smaller compared with diameters of arteries from either untreated or OVX + EST females. In the presence of N G-nitro-l-arginine methyl ester, artery diameters decreased in all groups, but diameters remained significantly smaller in arteries from males and OVX females compared with untreated and OVX + EST females. After endothelium removal or when inhibition of nitric oxide synthase and cyclooxygenase were combined, differences in diameters of arteries from OVX and OVX + EST were abolished. These data suggest that chronic estrogen treatment modulates myogenic reactivity of mouse cerebral arteries through both endothelium-derived cyclooxygenase- and nitric oxide synthase-dependent mechanisms.

Endothelium-dependent vasodilation of cerebral arteries is altered with simulated microgravity through nitric oxide synthase and EDHF mechanisms

2006 ◽  
Vol 101 (1) ◽  
pp. 348-353 ◽  
Author(s):  
Rhonda D. Prisby ◽  
M. Keith Wilkerson ◽  
Elke M. Sokoya ◽  
Robert M. Bryan ◽  
Emily Wilson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
Cerebral Perfusion ◽  
Simulated Microgravity ◽  
Cerebral Arteries ◽  
Caveolin 1 ◽  
Fluid Shifts ◽  
Oxide Synthase

Cephalic elevations in arterial pressure associated with microgravity and prolonged bed rest alter cerebrovascular autoregulation in humans. Using the head-down tail-suspended (HDT) rat to chronically induce headward fluid shifts and elevate cerebral artery pressure, previous work has likewise shown cerebral perfusion to be diminished. The purpose of this study was to test the hypothesis that 2 wk of HDT reduces cerebral artery vasodilation. To test this hypothesis, dose-response relations for endothelium-dependent (2-methylthioadenosine triphosphate and bradykinin) and endothelium-independent (nitroprusside) vasodilation were determined in vitro in middle cerebral arteries (MCAs) from HDT and control rats. All in vitro measurements were done in the presence and absence of the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (10−5 M) and cyclooxygenase inhibitor indomethacin (10−5 M). MCA caveolin-1 protein content was measured by immunoblot analysis. Endothelium-dependent vasodilation to 2-methylthioadenosine triphosphate and bradykinin were both lower in MCAs from HDT rats. These lower vasodilator responses were abolished with NG-nitro-l-arginine methyl ester but were unaffected by indomethacin. In addition, HDT was associated with lower levels of MCA caveolin-1 protein. Endothelium-independent vasodilation was not altered by HDT. These results indicate that chronic cephalic fluid shifts diminish endothelium-dependent vasodilation through alterations in the endothelial nitric oxide synthase signaling mechanism. Such decrements in endothelium-dependent vasodilation of cerebral arteries could contribute to the elevations in cerebral vascular resistance and reductions in cerebral perfusion that occur after conditions of simulated microgravity in HDT rats.

Endothelial-mediated dilations of rat middle cerebral arteries by ATP and ADP

1997 ◽  
Vol 273 (3) ◽  
pp. H1472-H1477 ◽  
Author(s):  
J. You ◽  
T. D. Johnson ◽  
W. F. Childres ◽  
R. M. Bryan
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
Cerebral Arteries ◽  
Nitric Oxide Synthase Inhibitor ◽  
Middle Cerebral Arteries ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Maximum Removal

The hypothesis that ATP and ADP produce dilations of rat middle cerebral arteries (MCAs) by different mechanisms was tested. Vessel diameters were measured from pressurized, perfused MCAs after application of different agonists. The luminal administration of ATP and ADP elicited concentration-dependent dilations (35% maximum). Removal of endothelium abolished the dilation to intraluminal ATP and attenuated the dilation to intraluminal ADP. The dilations to ATP were abolished with N omega-nitro-L-arginine methyl ester (L-NAME; 10 microM), a nitric oxide synthase inhibitor, at ATP concentrations of 1 microM and below. However, at concentrations of 10 microM ATP and above, L-NAME had no effect on the response. The dilations to ADP were attenuated by L-NAME to the same degree as removal of endothelium. The mechanism for dilation by ATP was identical to that of UTP, a selective P2u purinoceptor agonist. The mechanism of dilation by ADP was similar to that of 2-methylthioadenosine 5'-triphosphate, a selective P2y purinoceptor agonist. We conclude that ATP and ADP elicit dilations of rat MCA by different mechanisms. ATP and ADP likely stimulate P2u and P2y purinoceptors, respectively.

Dilation of rat diaphragmatic arterioles by flow and hypoxia: roles of nitric oxide and prostaglandins

1999 ◽  
Vol 86 (5) ◽  
pp. 1644-1650 ◽  
Author(s):  
Michael E. Ward
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
Concurrent Treatment ◽  
Nitric Oxide Release ◽  
Luminal Flow ◽  
Hypoxic Vasodilation ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

The in vitro responses to ACh, flow, and hypoxia were studied in arterioles isolated from the diaphragms of rats. The endothelium was removed in some vessels by low-pressure air perfusion. In endothelium-intact arterioles, pressurized to 70 mmHg in the absence of luminal flow, ACh (10−5 M) elicited dilation (from 103 ± 10 to 156 ± 13 μm). The response to ACh was eliminated by endothelial ablation and by the nitric oxide synthase antagonists N G-nitro-l-arginine (l-NNA; 10−5 M) and N G-nitro-l-arginine methyl ester (l-NAME, 10−5 M) but not by indomethacin (10−5 M). Increases in luminal flow (5–35 μl/min in 5 μl/min steps) at constant distending pressure (70 mmHg) elicited dilation (from 98 ± 8 to 159 ± 12 μm) in endothelium-intact arterioles. The response to flow was partially inhibited byl-NNA,l-NAME, and indomethacin and eliminated by endothelial ablation and by concurrent treatment withl-NAME and indomethacin. The response to hypoxia was determined by reducing the periarteriolar[Formula: see text] from 100 to 25–30 Torr by changing the composition of the gas used to bubble the superfusing solution. Hypoxia elicited dilation (from 110 ± 9 to 165 ± 12 μm) in endothelium-intact arterioles but not in arterioles from which the endothelium had been removed. Hypoxic vasodilation was eliminated by treatment with indomethacin and was not affected byl-NAME orl-NNA. In rat diaphragmatic arterioles, the response to ACh is dependent on endothelial nitric oxide release, whereas the response to hypoxia is mediated by endothelium-derived prostaglandins. Flow-dilation requires that both nitric oxide and cyclooxygenase pathways be intact.

Evidence that nitric oxide synthase is involved in progesterone-induced acrosomal exocytosis in mouse spermatozoa

1997 ◽  
Vol 9 (4) ◽  
pp. 433 ◽  
Author(s):  
María Beléen Herrero ◽  
J. Marcelo Viggiano ◽  
Silvina Pérez Martínez ◽  
Martha F. de Gimeno
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
No Synthase ◽  
Nitric Oxide Donor ◽  
Mouse Sperm ◽  
Acrosomal Exocytosis ◽  
Oxide Synthase ◽  
Spermine Nonoate

In a recent work, we detected nitric oxide synthase (NO synthase) in the acrosome and tail of mouse and human spermatozoa by an immunofluorescence technique. Also, NO-synthase inhibitors added during sperm capacitationin vitro reduced the percentage of oocytes fertilized in vitro, suggesting a role for NO synthase in sperm function. Therefore, in the present study the effect of three NO-synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME), NG-nitro-D-arginine methyl ester (D-NAME) and L-NG-nitro-arginine (NO2-arg), and of a nitric oxide donor, spermine-NONOate, on the progesterone-induced acrosome reaction of mouse sperm was examined. NO-synthase inhibitors were added at 0, 60 or 90 min during capacitation; at 120 min, mouse epididymal spermatozoa were exposed to 15 µM progesterone for another 15 min. In another set of experiments, different concentrations of spermine-NONOate were added to capacitated spermatozoa for 15 min; in these experiments, progesterone was not included. NO2-arg and L-NAME blocked progesterone-induced exocytosis regardless of the time at which these inhibitors were added. Moreover, D-NAME did not inhibit exocytosis. In contrast, spermine-NONOate stimulated the acrosomal exocytosis in vitro directly. These results provide evidence that mouse sperm NO synthase participates in the progesterone-induced acrosome reactionin vitro and that nitric oxide induces this event.

Selected Contribution: Cerebrovascular NOS and cyclooxygenase are unaffected by estrogen in mice lacking estrogen receptor-α

2001 ◽  
Vol 91 (5) ◽  
pp. 2391-2399 ◽  
Author(s):  
Greg G. Geary ◽  
Anne Marie McNeill ◽  
Jose A. Ospina ◽  
Diana N. Krause ◽  
Kenneth S. Korach ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cerebral Artery ◽  
Endothelial Nitric Oxide Synthase ◽  
Cerebral Arteries ◽  
Estrogen Treatment ◽  
Wild Type ◽  
Cyclooxygenase 1 ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Estrogen alters reactivity of cerebral arteries by modifying production of endothelium-dependent vasodilators. Estrogen receptors (ER) are thought to be involved, but the responsible ER subtype is unknown. ER-α knockout (αERKO) mice were used to test whether estrogen acts via ER-α. Mice were ovariectomized, with or without estrogen replacement, and cerebral blood vessels were isolated 1 mo later. Estrogen increased levels of endothelial nitric oxide synthase and cyclooxygenase-1 in vessels from wild-type mice but was ineffective in αERKO mice. Endothelium-denuded middle cerebral artery segments from all animals constricted when pressurized. In denuded arteries from αERKO but not wild-type mice, estrogen treatment enhanced constriction. In endothelium-intact, pressurized arteries from wild-type estrogen-treated mice, diameters were larger compared with arteries from untreated wild-type mice. In addition, contractile responses to indomethacin were greater in arteries from wild-type estrogen-treated mice compared with arteries from untreated wild-type mice. In contrast, estrogen treatment of αERKO mice had no effect on diameter or indomethacin responses of endothelium-intact arteries. Thus ER-α regulation of endothelial nitric oxide synthase and cyclooxygenase-1 pathways appears to contribute to effects of estrogen on cerebral artery reactivity.

Loss of nitric oxide synthase immunoreactivity in cerebral vasospasm

1996 ◽  
Vol 84 (4) ◽  
pp. 648-654 ◽  
Author(s):  
Ryszard M. Pluta ◽  
B. Gregory Thompson ◽  
Ted M. Dawson ◽  
Solomon H. Snyder ◽  
Robert J. Boock ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cerebral Vasospasm ◽  
Cerebral Artery ◽  
Cerebral Arteries ◽  
Nerve Fibers ◽  
Content Type ◽  
The Right ◽  
Oxide Synthase ◽  
Fine Print

✓ To determine the distribution of nitric oxide synthase (NOS) in the primate cerebral artery nervi vasorum and to examine the potential role of NOS in cerebral vasospasm after subarachnoid hemorrhage (SAH) in primates, the distribution of NOS immunoreactivity (NOS-IR) in the major cerebral arteries was examined immunohistochemically in cynomolgus monkeys by the use of whole, mounted preparations of the circle of Willis. In four normal monkeys, NOS-IR was localized to the endothelial and adventitial layers of the large cerebral arteries. On the abluminal side, NOS-IR staining was densely concentrated in perivascular nerve fibers (nervi vasorum) of the anterior circulation. Staining was less prominent in the posterior circulation. In six monkeys with vasospasm on Day 7 after placement of preclotted arterial blood to form an SAH around the right middle cerebral artery (MCA) (42% ± 8.3% decrease of MCA area, mean ± standard deviation), NOS-IR was virtually absent in nerve fibers around the spastic right MCA but was normal on the contralateral side. In five monkeys in which vasospasm resolved by Day 14 after SAH (36% ± 14% decrease of right MCA area on Day 7, and 5% ± 14% decrease on Day 14), NOS-IR was also absent in the right MCA adventitial nerve fibers and remained normal in the left MCA. Adventitial NOS-IR was also normal in cerebral vessels of a sham-operated, nonspastic monkey. These findings provide further evidence that nitric oxide (NO) functions as a neuronal transmitter to mediate vasodilation in primates and indicate a role for adventitial NO in the pathogenesis of cerebral vasospasm after SAH in humans.

Simulated microgravity increases myogenic tone in rat cerebral arteries

1998 ◽  
Vol 85 (5) ◽  
pp. 1615-1621 ◽  
Author(s):  
Greg G. Geary ◽  
Diana N. Krause ◽  
Ralph E. Purdy ◽  
Sue P. Duckles
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
Simulated Microgravity ◽  
Cerebral Arteries ◽  
Myogenic Tone ◽  
Physiological Salt Solution ◽  
Nitric Oxide Synthase Inhibitor ◽  
Oxide Synthase ◽  
And Control

Adaptation of the cerebral circulation to microgravity was investigated in rat middle cerebral arteries after 20 days of hindlimb unweighting (HU). Myogenic responses were measured in isolated, pressurized arteries from HU and control animals. Maximal passive lumen diameters, obtained in the absence of extracellular Ca2+ plus EDTA, were not significantly different between groups (249 vs. 258 μm). In physiological salt solution, arteries from both HU and control animals maintained a constant lumen diameter when subjected to incremental increases in transmural pressure (20–80 mmHg). However, the diameter of arteries from HU animals was significantly smaller than that of arteries from control animals at all pressures; this difference could be eliminated by exposure to the nitric oxide synthase inhibitor N G-nitro-l-arginine methyl ester. After HU treatment, transient distensibility of the artery wall in response to pressure was also significantly decreased, whereas the frequency and amplitude of vasomotion were increased. The latter changes were not affected by N G-nitro-l-arginine methyl ester. Thus simulated microgravity increases cerebral artery myogenic tone through both nitric oxide synthase-dependent and -independent mechanisms.

scholarly journals Neuronal Nitric Oxide Synthase Activation by Vasoactive Intestinal Peptide in Bovine Cerebral Arteries

1997 ◽  
Vol 17 (9) ◽  
pp. 977-984 ◽  
Author(s):  
Carmen González ◽  
Carla Barroso ◽  
Carmen Martín ◽  
Sergio Gulbenkian ◽  
Carmen Estrada
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Vasoactive Intestinal Peptide ◽  
Cerebral Artery ◽  
Cyclic Gmp ◽  
Nerve Stimulation ◽  
Cerebral Arteries ◽  
Neuronal Nitric Oxide Synthase ◽  
Nerve Fibers ◽  
Oxide Synthase

The participation of nitric oxide and vasoactive intestinal peptide (VIP) in the neurogenic regulation of bovine cerebral arteries was investigated. Nitrergic nerve fibers and ganglion-like groups of neurons were revealed by NADPH-diaphorase staining in the adventitial layer of bovine cerebral arteries. NADPH diaphorase also was present in endothelial cells but not in the smooth muscle layer. Double immunolabeling for neuronal nitric oxide synthase and VIP indicated that both molecules co-localized in the same nerve fibers in these vessels. Transmural nerve stimulation (200 mA, 0.2 milliseconds, 1 to 8 Hz) of endothelium-denuded bovine cerebral artery rings precontracted with prostaglandin F2α, produced tetrodotoxin-sensitive relaxations that were completely suppressed by NG-nitro-l-arginine methyl ester (l-NAME) and by the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline (ODQ), but were not affected by the adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22,536), nor by VIP tachyphylaxis induced by pretreatment with 1 μmol/L VIP. Transmural nerve stimulation also elicited increases in intracellular cyclic GMP concentration, which were prevented by l-NAME, and small decreases in intracellular cyclic AMP concentration. Addition of VIP to bovine cerebral artery rings without endothelium produced a concentration-dependent relaxation that was partially inhibited by l-NAME, ODQ, and SQ 22,536. The effects of l-NAME and SQ 22,536 were additive. VIP induced a transient increase in intracellular cyclic GMP concentration, which was maximal 1 minute after VIP addition, when the highest relaxation rate was observed, and which was blocked by l-NAME. It is concluded that nitric oxide produced by perivascular neurons and nerve fibers fully accounts for the experimental neurogenic relaxation of bovine cerebral arteries and that VIP, which also is present in the same perivascular fibers, acts as a neuromodulator by activating neuronal nitric oxide synthase.

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