Effects of bufalin on norepinephrine turnover in canine saphenous vein.
Abundant experimental data suggest that an endogenous digitalislike factor is responsible for some essential hypertension. Some forms of hypertension have also been associated with increased levels of catecholamines. We therefore designed experiments to investigate the role of digitalislike factors in the regulation of norepinephrine turnover in the neurovascular junction. We chose bufalin, an amphibian-derived compound that shares many of the physiological properties postulated as characteristic of digitalislike compounds, as a model of the mammalian compound. In vitro experiments in canine saphenous veins showed that, in addition to inhibiting norepinephrine uptake, bufalin increased norepinephrine overflow by an amount larger than could be explained solely by uptake inhibition. The effect of bufalin on norepinephrine overflow is inhibited by tetrodotoxin, which suggests a dependence of this response on Na+ influx through the neuronal membranes. We propose that Na+,K(+)-ATPase inhibition resulting in neuronal depolarization is responsible for the augmented norepinephrine turnover caused by bufalin and that these indirect effects of norepinephrine on the cardiovascular system may play a role in the etiology of hypertension.
Cress
L W
LW
Department of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Freas
W
W
Haddy
F
F
Muldoon
S M
SM
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D002018:Bufanolides / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D012501:Saphenous Vein / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013779:Tetrodotoxin / Q000494:pharmacology
D002018:Bufanolides; D013779:Tetrodotoxin; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; C022777:bufalin; D009638:Norepinephrine