M.S. (Master of Science)
Department of Biological Sciences
Vasodilators; Ganglionic blocking agents
The vasodilator and ganglionic blocking effects of N-acetylprocainamide (NAPA) were examined in the femoral vascular bed and gracilis muscle preparation in the dog. In an attempt to elucidate the mechanism of NAPA's hypotensive action, the following hypotheses were tested. 1) Intraarterial infusion of NAPA in the femoral artery of the dog causes vasodilatation. 2) NAPA causes sympathetic ganglionic blockade in the dog. 3) NAPA's hypotensive and ganglionic blocking effects exhibit similar kinetics. NAPA's vasodilator effect was tested by infusing NAPA intraarterially into the femoral bed. Vasodilatation was measured by monitoring blood flow with electromagnetic flow probes, under conditions of constant perfusion pressure. The ganglionic blocking properties of NAPA were examined using the gracilis muscle preparation in dogs. Sympathetic preganglionic and postganglionic nerves to the muscle were stimulated before, during and after NAPA infusion. Nerve stimulation-induced changes in perfusion pressure to the gracilis muscle (at constant flow) were monitored as indicators of vasoconstrictor responses and ganglionic blockade. The hypotensive effects and ganglionic blockade were correlated with NAPA concentrations using pharmacokinetic modeling of NAPA plasma concentration data. Sodium nitroprusside, a control direct smooth muscle vasodilator, increased flow and decreased resistance whereas NAPA did not exhibit direct vasodilator actions in the femoral vascular bed in concentrations up to 484 ug/ml in femoral arterial blood. In addition, when a NAPA dose of 60 mg/kg was given intravenously, NAPA caused a significant decrease in systemic mean arterial pressure (MAP) which could be correlated with sympathetic ganglionic blockade in the gracilis muscle preparation. NAPA caused a decrease in the vasoconstrictor response to sympathetic preganglionic stimulation as opposed to the lack of effect on sympathetic postganglionic vasoconstrictor responses. It was therefore concluded that NAPA is not a direct vasodilator but instead causes hypotension through ganglionic blockade. Pharmacokinetic analysis indicated that NAPA plasma concentrations decreased in a triexponential fashion with time. NAPA distribution and elimination could be fitted to a three-compartment mamillary model previously proposed for NAPA distribution and elimination in man. In this study, correlation of the hypotensive and ganglionic blocking effects with the pharmacokinetics of NAPA's distribution and elimination suggests that the site of drug action is more closely related to the fast equilibrating compartment than to concentrations in the central or slow equilibrating compartments of this model.
Eudeikis, James R., "Studies on the vasodilator and ganglionic blocking actions of N-acetylprocainamide in the dog" (1981). Graduate Research Theses & Dissertations. 5107.
ix, 82 pages
Northern Illinois University
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