Pial Artery Responses to Norepinephrine Potentiated by Endothelium Removal

Abstract

Laboratoire de Physi% Rie et Physio{Jath% Rie Cc'rchrova.l'cu/aire, I NSERM U 182, CNRS ERA 361, Unil'ersite Paris VII, Paris, alld *Lahoratoire de P/wrmac% Rie, UER Mcdecine et Pharmacie, Ullil'ersitc de LimoRcs, LimoRe.l', France Summary: The effect of endothelium removal on pial ar tery constriction in response to norepinephrine (NE) was studied in vitro using a perfused vessel setup in which pressure increases indicate vasoconstriction, In deen dothelialized rabbit arteries, the reaction to extraluminal NE was found to be characterized by a much higher E max (2,0 times) and a slight (but significant) leftward shift of the concentration-response curve (lower EC50) compared with control vessels. In cat arteries subjected to either extra-or intraluminal NE, the E max was also substantially A few years ago, Furchgott and Zawadzki (1980) showed that the presence of the endothelium was an essential condition for obtaining relaxation of rabbit thoracic aorta strips in response to acetyl choline. Since then, many studies have confirmed the essential role of the endothelium in vasodilata tions induced by various agents and in a variety of preparations [see Furchgott (1983) for review].In contrast to this burgeoning literature on dilator agents, very few reports (e.g., Cocks and Angus, 1983;Egleme et al., 1984) have appeared on con strictor agents and the influence of the endothelium, and none deal with cerebral vessels. It seemed im portant to us to determine whether vasoconstrictor responses in the cerebral circulation could be influ enced by the vascular endothelium since naturally occurring agents such as norepinephrine (NE) and serotonin are known to be released during (patho)physiological phenomena such as vaso spasm (du Boulay et aI., 1983;Cook, 1984) of any kind of lesion or alteration of the endothelial lining such as is present in atherosclerosis. In this article, we report the influence of removing the en dothelium on the response of rabbit and cat pial arteries to NE. MATERIALS AND METHODSFauve de Bourgogne rabbits or European-type cats were anesthetized and decapitated. The brain was rapidly removed and placed in a dish containing a physiological solution of the following composition (mM): NaCI 119, KCI 5, CaCl1 0.75, MgCl, 1.2, NaH,P04 1, NaHCO, 1, N-2-hydroxy e thyl piperazi n e-N-2-eth a nesulfonic acid 25; with pH adjusted to 7.4 at 20°C. This solution was pre ferred to a bicarbonate-buffered Krebs solution for the preparation since the pH was more constant (not depen dent on CO, saturation). The main branches of the middle cerebral ar t eries (MCAs) were ligated over a length of � 10 mm in the rabbit and 15 mm in the cat, starting at the circle of Willis. The endothelium of one of each pair of arteries was removed by rubbing the intimal surface with a stainless-steel tube of appropriate diameter in serted completely through the lumen. The arteries were then cannulated with a short stainless-steel tube, re moved from the brain, and placed in a 50-mt organ bath at 37°C where they were connected to a ...

Endothelium-dependent constriction demonstrated in vivo in mouse cerebral arterioles.

“…However, in brain vessels of other species, norepinephrine was found to produce endothelium-dependent dilation rather than a constriction. 38 Serotonin has generally been found to produce an endothelium-dependent relaxing effect that counters a direct constricting action of serotonin on vascular smooth muscle. However, the net effect of the opposing forces is usually constriction.…”

Early changes in rabbit cerebral artery reactivity after subarachnoid hemorrhage.

“…13 Three-millimeter segments of the vertebral artery (VA) (10-minute series only), BA, and middle cerebral artery (MCA) were removed under a surgical microscope. The artery segments were then placed in 5-ml organ baths 14 containing a solution of the following millimolar composition: 126 NaCl, 5 KC1, 1.2 NaH 2 PO 4 , 1.3 MgCl 2 , 20 NaHCO 3 , 2.5 CaCl 2 , and 5.5 glucose and were gassed with 4% CO 2 /20% O 2 /76% N 2 with a pH of 7.3-7.4.…”

Leukocyte-induced acute endothelial dysfunction in middle cerebral artery in rabbits. Response to aggregating platelets.

“…After decapitation, the brain was removed and placed in a physiological solution as previously described. 22 - 23 Three-millimeter segments of MCA were removed under a surgical microscope and placed in 5-mL organ baths containing a solution of the following millimolar composition: 126 NaCl, 5 KC1,1.2 NaH 2 PO 4 ,1.3 MgCl 2 ,15 NaHCO 3 , 2.5 CaCl 2 , and 5.5 glucose; the solution was gassed with 4% CO 2 /20% O 2 /76% N 2 with a pH of 7.3 to 7.4. The segments, mounted on L-shaped holders, were allowed to equilibrate for 90 minutes at 37°C before the isometric tension measurements were begun.…”