A new method for determination of drug effects on the arterial distensibility on conscious dogs
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1Department of Pharmacology, Schwarz GmbH Monheim, F.R.G.
Abstract:
We developed a method for recording drug effects on the distensibility of the arterial system on conscious catheterized beagle dogs. Assuming a pressure-dependent volumic flow from the large arteries into the peripheral vessels, the volume-elasticity of the arterial windkessel is computed by the time-course of the diastolic pressure decline and the total peripheral resistance. A continuous recording of this parameter shows a rapid decrease during each diastolic relaxation, which was in agreement with studies on isolated arteries. An elevation of the mean pressure by an infusion of angiotensin I causes an increase of the elasticity. However, nitroglycerin administration (5 micrograms/kg/min) reduced this parameter significantly. Simultaneous recording of the pulse-wave velocity, which is a measure of the elastic modulus of the arterial wall suggests that nitroglycerin-induced enhancement of the arterial elasticity is caused by a reduced stiffness of the arterial walls as well as by an increased volume of the windkessel. The effects of the nitroglycerin infusion on the venous system and the pulmonary artery showed a faster onset than the decrease of the arterial elasticity. However, the venous effect showed a significant drug tolerance, whereas enhancement of the arterial distensibility remained constant.