Separation of antihypertensive from ganglioplegic effects of felodipine in the cat.
The effects of felodipine on sympathetic ganglionic transmission and on the effector responses of two muscle models were studied. In anesthetized cats we established what injected dose and plasma levels of this selectively vasodilating dihydropyridine were necessary for the neural and for the primary hypotensive effects on arterial blood pressure in vivo. Felodipine in cats reduced mean arterial pressure at a dose of 0.010 mumol/kg i.v., corresponding to a plasma concentration of 10 nmol/L. A 15-25-fold higher dose, or plasma concentration, was required to produce a significant reduction in the amplitude of the sympathetic postganglionic action potential (PAP). The latencies of the PAPs remained constant. Felodipine in vitro did not attenuate the neurogenic response of the nictitating membrane. However, the spontaneous activity, as well as the neurogenic response of the portal vein, was inhibited by felodipine in nanomolar concentrations. Felodipine at the highest dose caused a small but significant attenuation of the postganglionic nictitating membrane response in vivo. This reduction was of insufficient magnitude to account alone for the diminution of the response to preganglionic stimulation. We conclude that felodipine in low concentrations reduces blood pressure by a direct relaxation of vascular smooth muscle, while, in addition, at high concentrations a partial ganglionic blockade may be induced.
L W
LW
Reinish
B
B
Ljung
R S
RS
Tuttle
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004562:Electrocardiography; D015736:Felodipine; D005260:Female; D005728:Ganglia, Sympathetic / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009541:Nictitating Membrane / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D009543:Nifedipine; D015736:Felodipine