Inhibition of the acetylcholine-induced relaxation of canine isolated basilar artery by potassium-conductance blockers

1991 ◽  
Vol 69 (6) ◽  
pp. 786-791 ◽  
Author(s):  
D. A. Elliott ◽  
M. Gu ◽  
B. Y. Ong ◽  
D. Bose
Keyword(s):  
Smooth Muscle ◽  
Sodium Nitroprusside ◽  
Basilar Artery ◽  
Sodium Pump ◽  
Potassium Conductance ◽  
K Channel ◽  
Relaxing Factor ◽  
Mechanical Removal ◽  
Canine Basilar Artery ◽  
Endothelium Derived Relaxing Factor

Canine basilar artery rings precontracted with 5-hydroxytryptamine (0.1–0.5 μM) relaxed in the presence of acetylcholine (25–100 μM), sodium nitroprusside (0.1 μM), or stimulation of the electrogenic sodium pump by restoration of extracellular K+ (4.5 mM) after K+- deprivation. Acetylcholine-induced relaxation is believed to be caused by the release of endothelium-derived relaxing factor (EDRF) and is prevented by mechanical removal of the endothelium, while relaxations induced by sodium nitroprusside or restarting of the sodium pump are endothelium-independent. Acetylcholine-induced relaxation was selectively blocked by pretreatment of the tissue with the nonselective K+ conductance inhibitors, 4-aminopyridine (4-AP, 3 mM), Ba2+ (1 mM), and tetraethylammonium (20 mM). 4-AP also blocked ACh-mediated relaxation in muscles contracted with elevated external K+. Relaxation of 5-hydroxytryptamine-induced contraction by sodium nitroprusside, or by addition of K+ to K+-deprived muscle, was not affected by 4-AP. Relaxation of basilar artery with acidified sodium nitrite solution (containing nitric oxide) was reduced by 4-AP. These results suggest that 4-AP and possibly Ba2+ inhibit acetylcholine-induced endothelium-dependent relaxation by inhibition of the action of EDRF on the smooth muscle rather than through inhibition of release of EDRF. The increase in K+ conductance involved in acetylcholine-induced relaxation is not due to ATP-inhibited K+ channels, as it is not blocked by glyburide (10−6 M). Endothelium-derived relaxant factor(s) may relax smooth muscle by mode(s) of action different from that of sodium nitroprusside or by hyperpolarization due to the electrogenic sodium pumping. Since 4-AP and similar agents are used to increase myogenic tone, the absence of the endothelium may be mistakenly assumed in the presence of these agents.Key words: Ba2+, blood vessels, endothelium-derived hyperpolarizing factor, endothelium-derived relaxing factor, glyburide, K channel, pinacidil, relaxation.

Proximal and distal dog coronary arteries respond differently to basal EDRF but not to NO

1989 ◽  
Vol 256 (3) ◽  
pp. H828-H831 ◽  
Author(s):  
U. Hoeffner ◽  
C. Boulanger ◽  
P. M. Vanhoutte
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Sodium Nitroprusside ◽  
Coronary Arteries ◽  
Relaxing Factor ◽  
Prostaglandin F2 Alpha ◽  
Endothelium Derived Relaxing Factor

Experiments were designed to analyze the effects of endothelium-derived relaxing factor(s) (EDRF; released basally or on stimulation with acetylcholine) and nitric oxide (NO) on smooth muscle of coronary arteries of different diameter. During contractions of the bioassay ring evoked with prostaglandin F2 alpha, the relaxations caused by basal EDRF were greater in the distal than in the proximal coronary arteries, whereas there was no difference in response to the EDRF released by acetylcholine. During direct superfusion, NO caused similar relaxations in proximal and distal coronary artery rings. Optimal tension, prostaglandin F2 alpha-induced contractions, and relaxations caused by sodium nitroprusside were comparable in both preparations. In rings of proximal and distal coronary artery studied in organ chambers, acetylcholine caused comparable endothelium-dependent, whereas sodium nitroprusside and NO cause comparable endothelium-independent relaxations. These experiments indicate a difference in response of different-sized coronary arteries to basally released EDRF and suggest that the basally released factor differs from NO.

Similar responsiveness of smooth muscle of the canine basilar artery to EDRF and nitric oxide

1989 ◽  
Vol 257 (4) ◽  
pp. H1235-H1239 ◽  
Author(s):  
Z. S. Katusic ◽  
J. J. Marshall ◽  
H. A. Kontos ◽  
P. M. Vanhoutte
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Basilar Artery ◽  
Inhibitory Effect ◽  
Relaxing Factor ◽  
Basilar Arteries ◽  
Canine Basilar Artery ◽  
Endothelium Derived Relaxing Factor ◽  
Ly 83583 ◽  
Hemoglobin M

Experiments were designed to compare the reactivity of canine basilar arteries to endothelium-derived relaxing factor (EDRF) and nitric oxide. Preparations with endothelium activated by bradykinin were used to study relaxations induced with EDRF, whereas the inhibitory effect of nitric oxide was studied in preparations without endothelium. All experiments were performed in the presence of indomethacin. EDRF- and nitric oxide-induced relaxations were significantly augmented in the presence of superoxide dismutase plus catalase but were reduced in the presence of methylene blue, LY 83583, and hemoglobin. M & B 22984 did not affect relaxations to either EDRF or nitric oxide. These results indicate that in the canine basilar artery EDRF is not an oxygen-derived free radical. The similar responsiveness of the basilar artery to EDRF and nitric oxide is consistent with the proposal that in the canine basilar artery nitric oxide is the factor.

Release of endothelium-derived relaxing factor after subarachnoid hemorrhage

1989 ◽  
Vol 70 (1) ◽  
pp. 108-114 ◽  
Author(s):  
Phyo Kim ◽  
Robert R. Lorenz ◽  
Thoralf M. Sundt ◽  
Paul M. Vanhoutte
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Basilar Artery ◽  
Arginine Vasopressin ◽  
Autologous Blood ◽  
Relaxing Factor ◽  
Basilar Arteries ◽  
Endothelium Derived Relaxing Factor ◽  
Chronic Vasospasm ◽  
Endothelium Dependent Relaxation

✓ The purpose of this study was to determine the cause of the loss of endothelium-dependent relaxation observed in chronic cerebral vasospasm. A bioassay system was developed to measure the release of endothelium-derived relaxing factor (EDRF) from canine basilar arteries. Subarachnoid hemorrhage (SAH) was induced in dogs by two injections of autologous blood into the cisterna magna. Angiograms were performed on the 7th day after SAH to check the presence of chronic vasospasm. The animals were sacrificed on the 8th day, and in vitro experiments were performed on rings harvested from the basilar artery. These confirmed loss of endothelium-dependent relaxation in response to bradykinin and arginine vasopressin in the group with SAH. The basilar arteries were perfused with modified Krebs-Ringer solution. The perfusate was bioassayed with a ring of coronary artery without endothelium (bioassay ring). The release of the EDRF was detected by relaxation of the bioassay ring contracted with prostaglandin F2α. Arginine vasopressin and bradykinin added to the perfusate upstream of the basilar artery caused concentration-dependent release of the EDRF. The direct effect of these peptides on the smooth muscle of the bioassay ring was to cause contraction. The release of the EDRF was identical in basilar arteries from the control and the SAH groups. These results indicate that the release of the EDRF is not impaired during chronic vasospasm, and thus that the loss of the endothelium-dependent relaxation is due to a decreased transfer of the EDRF or a reduced responsiveness of the smooth muscle to the factor.

Mechanism of impaired myogenic response in cerebral blood vessels during posthypoxic recovery

1987 ◽  
Vol 65 (2) ◽  
pp. 159-164 ◽  
Author(s):  
B. A. Mallick ◽  
D. Bose ◽  
T. Chau ◽  
B. Y. Ong
Keyword(s):  
Smooth Muscle ◽  
Basilar Artery ◽  
Sodium Pump ◽  
Rapid Reduction ◽  
Bathing Medium ◽  
Tension Level ◽  
Electrogenic Sodium Pump ◽  
Muscle Inhibition ◽  
Canine Basilar Artery ◽  
Series Of Experiments

Cerebral blood flow autoregulation is impaired in newborn animals when a brief period of hypoxia is followed by normoxia. Because myogenic mechanisms are widely thought to be responsible for autoregulation, this study examined the effect of hypoxia and reoxygenation on the isometric mechanical function of isolated cerebral (basilar) arterial smooth muscle made to contract rhythmically and thus simulate the behaviour of arterioles. Although at rest a small amount of active tension was present in these preparations, this tension was further increased and the muscle was rendered spontaneously rhythmic by treatment with 4-aminopyridine. Reduction of bath [Formula: see text] from 120 to 25 mmHg (1 mmHg = 133.32 Pa) caused an increase in tension followed by a return towards normal tension. At this time rhythmic oscillations gradually decreased in amplitude. Restoration of normal oxygen tension caused a rapid reduction and an undershoot in tension followed by recovery to normal level. Two possible mechanisms for this undershoot, which may be due to a decrease in myogenic responsiveness and therefore of autoregulatory function, were tested. 8-Phenyltheophylline, an antagonist of adenosine receptors, caused a decrease in the inhibitory mechanical effects of adenosine (10−6–10− M). However, in the presence of 8-phenyltheophylline, there was no change in the undershoot in tension caused by reoxygenation, thus ruling out involvement of adenosine released from the vessel in smooth muscle inhibition due to hypoxia. In a separate series of experiments, the role of an electrogenic sodium pump in causing the undershoot was tested. Treatment with 5-hydroxytryptamine in a K+ -free bathing medium caused an increase in basilar artery tension. When normal potassium concentration was restored the muscle relaxed with a transient undershoot below the basal tension level. In muscle preparations pretreated with ouabain (3 × 10−6 M), the K+-induced undershoot was abolished and replaced by a transient contraction. The same concentration of ouabain decreased by 92% the tension undershoot caused by reoxygenation. These experiments rule out participation of adenosine released from the blood vessel in the loss of myogenic tone during reoxygenation. The data also indicate that reactivation of the sodium pump may be responsible to some extent for the undershoot in tone during reoxygenation of isolated canine basilar artery.

Dietary omega 3 fatty acids and endothelium-dependent relaxations in porcine coronary arteries

1989 ◽  
Vol 256 (4) ◽  
pp. H968-H973 ◽  
Author(s):  
H. Shimokawa ◽  
P. M. Vanhoutte
Keyword(s):  
Fatty Acids ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Polyunsaturated Fatty Acids ◽  
Eicosapentaenoic Acid ◽  
Coronary Arteries ◽  
Treated Group ◽  
Omega 3 ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

Dietary supplementation with cod-liver oil significantly augments endothelium-dependent relaxations in porcine coronary arteries. The present study was designed to examine the effect of dietary administration of omega 3 polyunsaturated fatty acids (mainly eicosapentaenoic acid, the major component of fish oil) on endothelium-dependent relaxations in porcine coronary arteries. Male Yorkshire pigs were maintained 4 wk on a regular diet with or without supplementation with purified eicosapentaenoic acid (3.5 g/day) and docosahexaenoic acid (1.5 g/day). Endothelium-dependent relaxations were examined in vitro. In rings from the treated group, endothelium-dependent relaxations were augmented in response to bradykinin, serotonin, and ADP, but not to the calcium ionophore A23187. These augmentations were not altered by indomethacin but were significantly inhibited by methylene blue, an inhibitor of guanylate cyclase. In the treated group, endothelium-dependent relaxations to aggregating platelets also were significantly augmented; platelet-induced contractions of quiescent rings were inhibited more by the presence of the endothelium than in arteries from the control group. Bioassay experiments demonstrated that the release of endothelium-derived relaxing factor(s) by bradykinin and relaxations of the vascular smooth muscle to the factor(s) were greater in arteries from the treated group. These observations indicate that dietary omega 3 polyunsaturated fatty acids augment receptor-operated endothelium-dependent relaxations, partly due to the augmented release of endothelium-derived relaxing factor(s) and partly due to the augmented relaxation of the vascular smooth muscle to the factor(s).

Enhanced release of endothelium-derived factor(s) by chronic increases in blood flow

1988 ◽  
Vol 255 (3) ◽  
pp. H446-H451 ◽  
Author(s):  
V. M. Miller ◽  
P. M. Vanhoutte
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Arteriovenous Fistula ◽  
Muscarinic Receptors ◽  
Femoral Artery ◽  
Response Curves ◽  
Femoral Arteries ◽  
Relaxing Factor ◽  
Bioassay System ◽  
Endothelium Derived Relaxing Factor

Chronic increases in blood flow caused by an arteriovenous fistula augment endothelium-dependent relaxations to acetylcholine. To determine whether endothelial muscarinic receptors are altered, concentration-response curves to acetylcholine were obtained in the presence of pirenzepine in fistula- and sham-operated canine femoral arteries. Pirenzepine inhibited the response to acetylcholine in both arteries. The pA2 (log Kb) for the antagonist was the same. A bioassay system was used to assess release of endothelium-derived relaxing factor. Rings of femoral artery (without endothelium) from unoperated dogs relaxed more when superfused with perfusate derived from endothelium of fistula-operated arteries during acetylcholine stimulation. Rings without endothelium of sham- and fistula-operated arteries relaxed to the same extent when superfused with perfusate derived from the endothelium of unoperated femoral arteries. These results suggest that augmented relaxations to acetylcholine in canine arteries where blood flow is chronically elevated do not result from changes in the subtype of endothelial muscarinic receptors or in the sensitivity of the underlying smooth muscle to endothelium-derived relaxing factor(s). They are likely due to increased release of endothelium-derived relaxing factor(s) on muscarinic activation.

Is nitric oxide the only endothelium-derived relaxing factor in canine femoral veins?

1989 ◽  
Vol 257 (6) ◽  
pp. H1910-H1916 ◽  
Author(s):  
V. M. Miller ◽  
P. M. Vanhoutte
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Superoxide Dismutase ◽  
Sodium Nitroprusside ◽  
Femoral Vein ◽  
Pulmonary Veins ◽  
Chemical Properties ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Ly 83583

Nitric oxide may be an endothelium-derived relaxing factor in systemic arteries and pulmonary veins. The endothelium-derived relaxing factor of systemic veins has not been characterized. Experiments were designed to determine whether the endothelium-derived relaxing factor of systemic veins shared chemical properties and mechanisms of action with nitric oxide. Rings of the canine femoral vein with and without endothelium were suspended in organ chambers for the measurement of isometric force. In rings without endothelium, relaxations to nitric oxide were augmented by superoxide dismutase plus catalase and were inhibited by hemoglobin, methylene blue, and LY 83583. The endothelium-dependent relaxations to acetylcholine and A23187 were not augmented by superoxide dismutase plus catalase but were inhibited by hemoglobin and only moderately reduced by either methylene blue or LY 83583. Relaxations to sodium nitroprusside were not inhibited by methylene blue and LY 83583. Relaxations to sodium nitroprusside were inhibited by ouabain and K+-free solution; those to nitric oxide were not. These results indicate that although the endothelium-derived relaxing factor released from canine systemic veins shares some chemical properties with nitric oxide, the mechanism by which relaxations are induced by the two differ. A factor dissimilar to nitric oxide but acting like sodium nitroprusside may be released by the endothelium of canine systemic veins.

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