scholarly journals Triphasic Response of Rat Intracerebral Arterioles to Increasing Concentrations of Vasopressin in vitro

1993 ◽  
Vol 13 (2) ◽  
pp. 304-309 ◽  
Author(s):  
Masakazu Takayasu ◽  
Yasukazu Kajita ◽  
Yoshio Suzuki ◽  
Masato Shibuya ◽  
Kenichiro Sugita ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Vascular Tone ◽  
Cerebral Arteries ◽  
Specific Inhibitor ◽  
In Vitro Study ◽  
Relaxing Factor ◽  
Pathological Conditions ◽  
Cerebral Arterioles ◽  
Endothelium Derived Relaxing Factor

To determine how vasopressin affects the vascular tone of the smaller cerebral arterioles, we carried out an in vitro study of isolated and cannulated intracerebral arterioles of rats. We found that increasing concentrations of vasopressin induced a triphasic response of vasodilation (10−12–10−11 M), vasoconstriction (10−10–10−8 M), and vasodilation stabilizing to control diameter (10−7–10−6 M) and that the maximum constriction was twice the maximum dilation in these smaller arterioles [21.2 ± 13.1% (mean ± SD) decrease in diameter vs. 11.2 ± 5.7% increase]. Pretreatment of the arterioles with NG-monomethyl-l-arginine (10−4 M), a specific inhibitor of endothelium-derived relaxing factor, abolished the vasopressin-induced vasodilation and significantly increased the vasoconstriction. These results suggest that these arterioles were maintained in a dilated state by an endothelium-derived relaxing factor activated by vasopressin. Both vasodilation and vasoconstriction were found to be mediated through vasopressin V1 receptors in a study of arterioles pretreated with d(CH2)5Tyr(Me)arginine vasopressin (10−6 M), a vasopressin V1 receptor antagonist. These results support the hypothesis that vasopressin may constrict smaller cerebral arterioles while simultaneously dilating larger cerebral arteries. Our results also suggest that vasopressin may aggravate cerebral ischemia in pathological conditions, such as subarachnoid hemorrhage, when the arteriolar response to vasopressin shifts from vasodilation to vasoconstriction due to increased vasopressin levels in plasma and CSF and impaired endothelium-derived relaxation.

Differences in endothelium-dependent cerebral dilation by bradykinin and acetylcholine

1990 ◽  
Vol 258 (5) ◽  
pp. H1261-H1266 ◽  
Author(s):  
H. A. Kontos ◽  
E. P. Wei ◽  
R. C. Kukreja ◽  
E. F. Ellis ◽  
M. L. Hess
Keyword(s):  
Hydroxyl Radical ◽  
Mechanism Of Action ◽  
Oxygen Radicals ◽  
Cerebral Microcirculation ◽  
Relaxing Factor ◽  
Cerebral Arterioles ◽  
Endothelium Derived Relaxing Factor ◽  
Endothelium Dependent Relaxation ◽  
Large Vessels

We compared the mechanism of action of acetylcholine and bradykinin, two agents that cause endothelium-dependent relaxation, on cerebral arterioles of cats equipped with cranial windows for the observation of the cerebral microcirculation. The vasodilation caused by bradykinin was eliminated by cyclooxygenase inhibition with topical indomethacin, it was reduced by topical deferoxamine, an agent that scavenges iron and thereby inhibits the production of hydroxyl radical via the Haber-Weiss reaction, and it was eliminated by 3-amino-1,2,4-triazole, an agent that inhibited superoxide production by cyclooxygenase. The vasodilation from acetylcholine was not affected by these agents. Acetylcholine induced a transferable, short-lived vasodilator material in bioassay experiments, whereas bradykinin did not. Bradykinin or acetylcholine, when applied topically by themselves, induced arteriolar dilation; when applied together, they did not. The findings are consistent with the view that the cerebral arteriolar dilation from bradykinin is caused by oxygen radicals generated in association with accelerated arachidonate metabolism via cyclooxygenase, whereas the dilation from acetylcholine is caused by an endothelium-derived relaxing factor (EDRF) similar to that generated by this agent in large vessels in vitro. The EDRF from acetylcholine and the radicals from bradykinin interact and inactivate each other.

Subarachnoid hemorrhage inhibition of endothelium-derived relaxing factor in rabbit basilar artery

1988 ◽  
Vol 69 (2) ◽  
pp. 247-253 ◽  
Author(s):  
Kazuhiro Hongo ◽  
Neal F. Kassell ◽  
Tadayoshi Nakagomi ◽  
Tomio Sasaki ◽  
Tetsuya Tsukahara ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Basilar Artery ◽  
Selective Inhibitor ◽  
Isometric Tension ◽  
The Other ◽  
Content Type ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Fine Print

✓ Vascular contractions in response to KCl and serotonin (5-hydroxytryptamine, 5-HT) in rabbit basilar artery were studied in vitro using an isometric tension-measurement technique. Hemoglobin ( 10−5 M) markedly augmented contractions induced by 5-HT (10−9 to 10−6 M) and slightly augmented those induced by KCl (20 to 80 mM) in arteries with intact endothelium. On the other hand, the augmentation induced by hemoglobin was almost abolished in arteries that were chemically denuded of endothelial cells by pretreatment with saponin. Since hemoglobin is known to be a selective inhibitor of endothelium-derived relaxing factor (EDRF), it is possible that the augmentation of contraction by hemoglobin in endothelium-intact arteries was mediated via an inhibition of spontaneously released EDRF. The effect of subarachnoid hemorrhage (SAH) on spontaneously released EDRF was investigated by injecting 5 ml of blood into the cisterna magna and sacrificing the rabbits 2 days later. Arteries after SAH showed a significant reduction in hemoglobin-induced augmentation compared to that seen in control arteries with intact endothelium. This result suggests that spontaneously released EDRF is significantly reduced after SAH. It is concluded that EDRF is released spontaneously in the rabbit basilar artery and that inhibition of its release might be involved in pathogenesis of cerebral vasospasm.

scholarly journals Endothelium-derived relaxing factor, nitric oxide: effects on and production by mesangial cells and the glomerulus.

1993 ◽  
Vol 3 (8) ◽  
pp. 1435-1441
Author(s):  
L Raij ◽  
P J Shultz
Keyword(s):  
Nitric Oxide ◽  
Vascular Tone ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

The endothelium-derived relaxing factor nitric oxide (EDRF/NO) is a labile, endogenous vasodilator that is important in the control of systemic vascular tone. This review focuses on the effects of EDRF/NO on glomerular mesangial cells in vitro and on the role of EDRF/NO in mesangial and glomerular physiology and pathophysiology in vivo. It was concluded that EDRF/NO can stimulate increases in cGMP, inhibit mesangial cell contraction, and inhibit growth factor-induced proliferation of mesangial cells in culture. Furthermore, incubation with endotoxin or cytokines stimulates mesangial cells to produce EDRF/NO, via an inducible NO synthase enzyme. Therefore, it is likely that NO could play a role in the inflammatory response within the glomerulus. Finally, recent studies providing evidence that EDRF/NO is functional within the glomerulus in vivo, especially during endotoxemia and inflammation are also reviewed.

Interaction of human platelets and leukocytes in modulation of vascular tone

1994 ◽  
Vol 266 (5) ◽  
pp. H1706-H1714 ◽  
Author(s):  
S. Kaul ◽  
B. J. Waack ◽  
R. C. Padgett ◽  
R. M. Brooks ◽  
D. D. Heistad
Keyword(s):  
Superoxide Anion ◽  
Polymorphonuclear Leukocytes ◽  
Vascular Tone ◽  
Carotid Arteries ◽  
Human Platelets ◽  
Vasomotor Tone ◽  
Relaxing Factor ◽  
In Vitro Activation ◽  
Endothelium Derived Relaxing Factor

We tested the hypothesis that the vasodilator response to human platelets is modulated by polymorphonuclear leukocytes (PMNs). Responses to platelets activated with thrombin, as well as PMNs activated with N-formylmethionyl-leucyl-phenylalanine (FMLP), were examined in perfused rabbit carotid arteries in vitro. Activation of platelets produced marked dilatation, and activation of PMNs produced modest constriction in arteries preconstricted with phenylephrine. Vasodilator responses to platelets were greatly impaired during infusion of activated PMNs. Pretreatment of PMNs with superoxide dismutase (SOD) partially restored dilator responses to platelets. Because SOD only partially restored vasodilator responses to platelets, we tested the possibility that adenosine-diphosphatase (ADPase) activity of PMNs may degrade ADP released by platelets and thus reduce vasodilator responses. After incubation with PMNs, dilator responses to ADP, but not acetylcholine, were significantly impaired. These findings indicate that vasodilatation produced by activated human platelets is profoundly impaired by activated leukocytes. We conclude that two mechanisms may account for this effect: 1) endothelium-derived relaxing factor, released in response to platelet-derived ADP, is inactivated by superoxide anion generated by activated PMNs and 2) ADP is degraded by ADPase activity of PMNs. We speculate that platelet-leukocyte interaction may have important effects on vasomotor tone.

Why is a new journal dedicated to vascular biology required?

2018 ◽  
Author(s):  
Paolo Madeddu
Keyword(s):  
Myocardial Ischemia ◽  
Tumor Growth ◽  
Vascular Tone ◽  
50Th Anniversary ◽  
Vascular Biology ◽  
Active Process ◽  
Master Regulators ◽  
Relaxing Factor ◽  
Tissue Healing ◽  
Endothelium Derived Relaxing Factor

The year 2018 marked the 110th anniversary of Goldmann’s discovery that vascularization is an active process in tissues1 and the 50th anniversary of the concomitant reports from Greenblatt and Shubik2 and Ehrmann and Knoth3 that soluble morphogenic factors are required for cancer angiogenesis. Many other radically transformative paradigms have been introduced in the last decades. To name a few, the molecular search for the identity of master regulators of vascular tone led to the discovery of the Endothelium-Derived Relaxing Factor (EDRF; i.e., NO4), while clinically inspired investigations led to the recognition of the pathophysiological relevance of neoangiogenesis in cancer and tissue healing. This brought about the proposal of blocking angiogenesis to halt tumor growth and stimulating angiogenesis to treat myocardial ischemia and heart failure5-7.

Modulation of cerebral arterial tone by endothelium-derived relaxing factor

1993 ◽  
Vol 264 (4) ◽  
pp. H1245-H1250 ◽  
Author(s):  
J. E. Brian ◽  
R. H. Kennedy
Keyword(s):  
Nitric Oxide ◽  
Muscle Tone ◽  
Cerebral Arteries ◽  
Maximum Tension ◽  
Relaxing Factor ◽  
Middle Cerebral Arteries ◽  
Endothelium Derived Relaxing Factor ◽  
Vascular Smooth Muscle Tone ◽  
Dose Dependent ◽  
Arterial Tone

This study was designed to further elucidate the role of the endothelium in regulation of cerebral vascular smooth muscle tone. Dose-dependent vasoconstrictive effects of serotonin (5-HT) were examined in endothelium-intact and endothelium-denuded ring segments prepared from canine basilar and middle cerebral arteries. Some preparations were pretreated with 10(-5) M N omega-nitro-L-arginine (L-NNA), an agent that inhibits the production of L-arginine-derived nitric oxide, one of the compounds proposed to be endothelium-derived relaxing factor. L-NNA alone elicited marked dose-dependent increases in tension in endothelium-intact preparations; a significantly smaller response was seen in endothelium-denuded preparations. The effects of L-NNA on endothelium-intact preparations were partially reversed by washing and treatment with L-arginine. The maximum tension induced by 5-HT was approximately doubled by removal of the endothelium as well as by L-NNA treatment of endothelium-intact preparations; a slight increase in maximum tension occurred in endothelium-denuded preparations treated with L-NNA. The concentration of 5-HT producing half-maximal contraction (ED50) was not affected by L-NNA. These data suggest that L-arginine-derived nitric oxide modulates canine cerebral arterial tone in both the resting state and during contraction with 5-HT.

Endothelium-derived relaxing factor in regulation of basal cardiopulmonary and renal function

1991 ◽  
Vol 261 (2) ◽  
pp. R323-R328 ◽  
Author(s):  
M. A. Perrella ◽  
F. L. Hildebrand ◽  
K. B. Margulies ◽  
J. C. Burnett
Keyword(s):  
Renal Function ◽  
Competitive Inhibitor ◽  
Vehicle Group ◽  
Relaxing Factor ◽  
Anesthetized Dogs ◽  
Endothelium Derived Relaxing Factor ◽  
Renal Vascular ◽  
Renal Responses

The endothelium has emerged as an important modulator of vascular tone by producing both vasodilating and vasoconstricting substances. In vitro studies have demonstrated that endothelial cells produce endothelium-derived relaxing factor (EDRF), which promotes vasodilation via the stimulation of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). However, the role of EDRF in the basal regulation of cardiopulmonary and renal function is not well defined. The present study was therefore designed to assess the function of EDRF by studying two groups of normal anesthetized dogs, of which one received a competitive inhibitor to EDRF generation, NG-monomethyl-L-arginine (L-NMMA; 50 micrograms.kg-1.min-1 iv), and the other received a vehicle. The L-NMMA infusion produced no significant increase in mean arterial pressure but marked increases in systemic, pulmonary, and renal vascular resistances compared with the vehicle group. Although renal blood flow decreased with L-NMMA, no changes were observed in glomerular filtration rate or sodium excretion. Associated with the cardiopulmonary and renal responses with L-NMMA was a modest increase in plasma endothelin (7.9 +/- 1.3 to 10.2 +/- 1.8 pg/ml, P less than 0.05), an endothelium-derived vasoconstrictor. No alteration was observed in plasma or urinary cGMP with EDRF inhibition. These cardiopulmonary and renal responses with L-NMMA may be attributed not only to EDRF inhibition but to an imbalance between endothelium-derived relaxing and contracting factors.

Effects of endothelium-derived relaxing factor and nitric oxide on rat mesangial cells

1990 ◽  
Vol 258 (1) ◽  
pp. F162-F167 ◽  
Author(s):  
P. J. Shultz ◽  
A. E. Schorer ◽  
L. Raij
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Mesangial Cells ◽  
Specific Inhibitor ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Functional Responses ◽  
Cross Sectional ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

We have investigated whether endothelium-derived relaxing factor (EDRF) and nitric oxide (NO), a substance proposed to be one of the EDRFs, could elicit biochemical and biological responses in rat glomerular mesangial cells (MC). In wells with MC alone, guanosine 3',5'-cyclic monophosphate (cGMP) levels were 2.6 +/- 0.6 fmol/microgram protein, and bradykinin did not affect these levels, whereas in coincubation experiments with bovine aortic EC and rat MC, cGMP levels in MC increased to 44.6 +/- 21 fmol/micrograms protein after bradykinin stimulation (P less than 0.05). This effect was potentiated by superoxide dismutase and inhibited by hemoglobin and L-NG-monomethyl arginine, a specific inhibitor of EDRF synthesis. Increases in cGMP were also observed when MC were incubated directly with NO and were potentiated by superoxide dismutase and inhibited by hemoglobin. We also tested whether NO could inhibit angiotensin II (ANG II)-induced reductions in cross-sectional area (CSA) of MC. When MC were exposed to ANG II only, 65% of the cells underwent a significant reduction in CSA, as measured by digital image analysis. However, when MC were incubated with ANG II and NO, only 10% of cells responded (P less than 0.04). These studies demonstrate that EDRF and NO induce significant biochemical and functional responses in rat glomerular MC and suggest that communication between EC and MC may be important in regulation of glomerular function.

Acute exposure to cholesterol increases arterial nitroprusside- and endothelium-mediated relaxation

1993 ◽  
Vol 264 (1) ◽  
pp. C32-C39 ◽  
Author(s):  
R. A. Bialecki ◽  
T. N. Tulenko
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Free Cholesterol ◽  
Molar Ratio ◽  
Relaxing Factor ◽  
Arterial Relaxation ◽  
Endothelium Derived Relaxing Factor ◽  
Arterial Endothelium ◽  
Muscle Responses

The effect of cholesterol enrichment on arterial relaxation was studied by evaluating sodium nitroprusside (SNP)- and endothelium-mediated relaxation of isolated rabbit carotid artery. Arterial segments were perfused in vitro (4 h) with cholesterol-rich liposomes consisting of free cholesterol (FC) and phospholipid (PL) in a 2:1 molar ratio. Ring segments from arteries exposed to cholesterol-rich liposomes exhibited a 60% increase (P < 0.01) in FC content without affecting PL content. Cholesterol-enrichment was associated with a twofold increase (r = 0.92, P < 0.05) in acetylcholine- and A23187-induced endothelium-mediated relaxation. Bioassay of endothelium-derived relaxing factor(s) (EDRF) after cholesterol exposure indicated that EDRF half-life and/or release increased (P < 0.05) threefold. A trend (P = 0.07) toward increased smooth muscle cell sensitivity to EDRF after cholesterol enrichment was also observed. Cholesterol enrichment increased (P < 0.05) sensitivity to SNP 12-fold, and this difference was further augmented (P < 0.01) twofold with endothelium removal. Cholesterol enrichment had no effect on relaxation to N2,2'-O-dibutyrylguanosine 3',5'-cyclic monophosphate. These data indicate that acute cholesterol enrichment increases EDRF activity from arterial endothelium and increases smooth muscle responses to both EDRF and SNP.

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