Local Regulation of Vascular Cross Section during Changes in Femoral Arterial Blood Flow in Dogs
TL;DR: The dilatation response occurred despite slight reductions in femoral blood pressure, and was present after ganglionic blockade, blockade of alpha and beta receptors with phenoxybenzamine and propranolol, atropinization and injection of an antihistamine.
Abstract: Diameters of the exposed femoral artery of anesthetized dogs were continuously measured with ultrasonic elements of lead zirconate titanate. In 13 of 16 dogs vascular diameters increased following a sudden increment in arterial blood flow induced by the injection of vasodilating agents (acetylcholine, histamine) peripheral to the recording level, by opening an arteriovenous shunt, or after tetanic stimulation of the sciatic nerve. The dilatation response occurred despite slight reductions in femoral blood pressure, and was present after ganglionic blockade, blockade of alpha and beta receptors with phenoxybenzamine and propranolol, atropinization and injection of an antihistamine. The dilatation response was also observed after transsection of the femoral artery distal to the recording level and is therefore not dependent on the retrograde propagation of nervous or myogenous impulses along the vascular wall.
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TL;DR: The Pharmacological Basis of Therapeutics, by Prof. Louis Goodman and Prof. Alfred Gilman, New York: The Macmillan Company, 1941, p.
Abstract: The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.
2,686 citations
TL;DR: It appears that the endothelium is essential for the compensatory arterial response to long-term changes in luminal blood flow rates.
Abstract: A 70 percent reduction in the rate of blood flow through the common carotid artery in rabbits caused a 21 percent decrease in the diameter of this artery within 2 weeks. The smooth muscle relaxant papaverine did not attenuate the response; therefore, such reductions in diameter probably reflect a structural modification of the arterial wall rather than sustained contraction of smooth muscle. This arterial response to reduced blood flow was abolished when the endothelium was removed from the vessels. It appears that the endothelium is essential for the compensatory arterial response to long-term changes in luminal blood flow rates.
1,102 citations
TL;DR: Results suggest that endothelial cells act as mediators of flow-dependent dilation in vasomotor response to increases in flow as observed in conduit arteries.
Abstract: Experiments were designed to investigate the importance of vascular endothelium in the vasomotor response to increases in flow as observed in conduit arteries (flow-dependent dilation). The diameter changes of femoral arteries (sonomicrometry) in response to increases in flow before and after endothelial damage procedures were studied in 23 dogs anesthetized with sodium pentobarbital. The functional integrity of the endothelial cells underneath the diameter sensors was tested by intra-arterial acetylcholine (local acetylcholine dilation) applied proximally to the sensors while a constant flow was maintained. Unilateral augmentation of femoral arterial flow (4.6 +/- 1.9-fold) induced by peripheral vasodilation or by arteriovenous shunt, elicited dilation (increase in diameter, 116 +/- 91 microns) in 18 of 23 dogs, whereas the diameter of the contralateral control artery was not affected. Mechanical removal of the endothelial cells by means of a balloon catheter abolished both the flow-dependent dilation and the local acetylcholine dilation, whereas the vasomotor responses to norepinephrine and nitroglycerin were not affected. Brief perfusions (1 minute) of the arteries with cell-free hydrogen peroxide solution (90 mM) also abolished the flow-dependent dilation and attenuated the local acetylcholine dilation (by 27 +/- 19%; p less than 0.02), while the responses to norepinephrine and nitroglycerin were not altered. These results suggest that endothelial cells act as mediators of flow-dependent dilation.
1,005 citations
TL;DR: The data suggest that transmission of a hyperpolarizing current from endothelium to the vascular smooth muscle is not necessary for flow-mediated vasodilation, and that activation of this channel leads to the release of the endogenous nitrovasodilator, nitric oxide.
Abstract: Flow-mediated vasodilation is endothelium dependent. We hypothesized that flow activates a potassium channel on the endothelium, and that activation of this channel leads to the release of the endogenous nitrovasodilator, nitric oxide. To test this hypothesis, rabbit iliac arteries were perfused at varying flow rates, at a constant pressure of60 mm Hg. Increments in flow induced proportional increases in vessel diameter, which were abolished by LN-mono-methylarginine (the antagonist of nitric-oxide synthesis). Barium chloride, depolarizing solutions ofpotassium, verapamil, calcium-free medium, and antagonists of the Kc. channel (charybdotoxin, iberiotoxin) also blocked flow-mediated vasodilation. Conversely, responses toother agonists of endothelium-dependent and independent vasodilation were unaffected by charybdotoxin or iberiotoxin. To confirm that flow activated a specific potassium channel to induce the release of nitric oxide, endothelial cells cultured on microcarrier beads were added to a flow chamber containing a vascular ring without endothelium. Flow-stimulated endothelial cells released a diffusible vasodilator, the degree of vasorelaxation was dependent upon the flow rate. Relaxation was abrogated by barium, tetraethylammonium ion, or charybdotoxin, but was not affected by apamin, glybenclamide, tetrodotoxin, or ouabain. The data suggest that transmission of a hyperpolarizing current from endothelium to the vascular smooth muscle is not necessary for flow-mediated vasodilation. Flow activates a potassium channel (possibly the Kc. channel) on the endothelial cell membrane that leads to the release ofnitric oxide. (J. Clin.
528 citations
Cites background from "Local Regulation of Vascular Cross ..."
...This phenomenon is directly dependent upon changes in flow, rather than pressure, and is mediated by a nonneurogenic local mechanism (2)....
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TL;DR: Observations indicate that fluid shear stress causes the generation of EDRF with properties of nitric oxide from aortic endothelial cells and that the bioassay system described may be useful for studying the mechanism of mechanochemical coupling that leads to Nitric oxide generation.
Abstract: An in vitro bioassay system was developed to study endothelium-mediated, shear stress-induced, or flow-dependent generation of endothelium-derived relaxing factor (EDRF). Monolayers of aortic endothelial cells were grown on a rigid and large surface area of microcarrier beads and were packed in a small column perfused with Krebs bicarbonate solution. The perfusate was allowed to superfuse three endothelium-denuded target pulmonary arterial strips arranged in a cascade. Fluid shear stress caused a flow-dependent release of EDRF from the endothelial cells. The action of EDRF was abolished by oxyhemoglobin and methylene blue, and the generation of EDRF in response to shear stress was markedly inhibited or abolished by NG-nitro-L-arginine, by NG-amino-L-arginine, by calcium-free extracellular medium, and by depleting endothelial cells of endogenous L-arginine. Addition of L-arginine to arginine-deficient but not arginine-containing endothelial cells rapidly restored the capacity of shear stress and bradykinin to generate EDRF. These observations indicate that fluid shear stress causes the generation of EDRF with properties of nitric oxide from aortic endothelial cells and that the bioassay system described may be useful for studying the mechanism of mechanochemical coupling that leads to nitric oxide generation.
501 citations
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17,697 citations
TL;DR: The Pharmacological Basis of Therapeutics, by Prof. Louis Goodman and Prof. Alfred Gilman, New York: The Macmillan Company, 1941, p.
Abstract: The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.
2,686 citations
"Local Regulation of Vascular Cross ..." refers background in this paper
...In other experiments, the dose of phenoxybenzamine was largely increased, but did not abolish die dilatation response, which was present even after the injection of 25 mg/kg, five times the recommended maximum dose (7) (dog 2, Table 1)....
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1,595 citations
TL;DR: My attention was first directed to these phenomena by the occurrence of curves like that reproduced in Fig. 11, which showed the effect of a fall of arterial pressure produced by exI citing the central end of the depressor nerve on the volume of the hind leg of the rabbit, the sciatic and the nerves accompanying the femoral artery having been cut.
Abstract: MY attention was first directed to these phenomena by the occurrence of curves like that reproduced in Fig. 11. In the course of experiments on vaso-dilator reflexes I sometimes observed what looked like a reflex of this kind, in a limb of which the nerves had been divided; the figure _ reproduced shows the effect of a fall of arterial pressure produced by exI citing the central end of the depressor nerve on the volume of the hind leg of the rabbit, the sciatic and the nerves accompanying the femoral artery having been cut. It will be noticed that as long as the fall of blood-pressure lasts there is a passive diminution of volume in the limb, but that as soon as the previous height of blood-pressure is attained, on cessation of the excitation, there is a considerable expansion of the limb lasting for some time. Such a curve would usually be explained by stating that Fig. 1. Effect of depressor excitation on there was present all through the volume of enervated leg. Upper curve blood-pressure, next below it volume of excitation a relaxration of the vessels, leg, upper of two chronographs-period but that it was prevented from showof excitation of depressor nerve, lower ing itself in an actual expansion of one-time in 10 sec. intervals. the limb by the simultaneous fall of blood-pressure; although it was
1,466 citations
"Local Regulation of Vascular Cross ..." refers background in this paper
...Since Bayliss (15) introduced the concept of vascular autoregulation by variations in transmural pressure, vascular resistance in several organs, especially the kidney, has been found to vary more or less in parallel with the perfusion pressure over a wide range of pressures....
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198 citations
"Local Regulation of Vascular Cross ..." refers background or methods or result in this paper
...In the present as in other studies (2-4) the increase in femoral flow was caused by stimulation of the sciatic nerve or by injection of a vasodilating agent....
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...The response shown to the left in Discussion Schretzenmayr (2), Fleisch (3), and Hilton (4) found by means of oncometry that the femoral artery of cats and dogs became wider when flow through the artery was increased....
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...Schretzenmayr (2), Fleisch (3), and Hilton (4) found that mechanical or chemical trauma to the arterial wall distal to the plethysmograph extinguished the response....
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...Hilton (4) believed he had provided final proof for retrograde conduction by dividing the femoral artery below the oncometer....
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...On this basis, Hilton (4) estimated the rate of propagation of the contractile wave to be approximately 10 cm/sec....
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