Nifedipine-induced inhibition of parasympathetic-mediated vasodilation in the orofacial areas of the cat

Hiroshi Izumi, Ikuko Nakamura
2000 American Journal of Physiology. Regulatory Integrative and Comparative Physiology  
Izumi, Hiroshi, and Ikuko Nakamura. Nifedipine-induced inhibition of parasympathetic-mediated vasodilation in the orofacial areas of the cat. Am J Physiol Regulatory Integrative Comp Physiol 279: R332-R339, 2000.-In anesthetized cats, we 1) compared the effects of antihypertensive agents (nifedipine, clonidine, phentolamine, propranolol, and nitroprusside) on the parasympathetic vasodilations elicited by lingual nerve (LN) stimulation in the lower lip and tongue and 2) investigated the
more » ... igated the mechanisms underlying the inhibitory effect of nifedipine on parasympathetic lower lip vasodilation. At the doses used, each antihypertensive agent reduced systemic arterial blood pressure by ϳ20 mmHg; however, the parasympathetic vasodilation elicited by LN stimulation was significantly reduced only by nifedipine. This inhibitory effect of nifedipine was not seen when LN was stimulated during ongoing repetitive stimulation of the superior cervical sympathetic trunk at 1-Hz frequency. This suggests that the ability of lip and tongue blood vessels to relax to parasympathetic stimulation is not directly impaired by this calcium channel blocker and that the inhibitory effects of nifedipine seen here probably resulted from an action on postsynaptic sites in vascular smooth muscle that caused a reduction in preexisting sympathetic vasoconstrictor tone (by inhibiting calcium influx into the vascular smooth muscle cell). antihypertensive agents; calcium antagonist; autonomic; blood vessels THE MAJOR CLINICAL USES OF calcium channel blocking agents lie in the field of therapy for hypertension and vascular insufficiency, particularly cardiac and cerebral (27) . The mechanism underlying their antihypertensive effects appears to involve an inhibition of ␣-adrenoceptor-mediated calcium entry into vascular smooth muscle (7) . Thus a reduction in the enhancing (vasoconstrictor) effect on vascular smooth muscle tone elicited by the norepinephrine released spontaneously from the nerve terminals of sympathetic vasoconstrictor fibers seems to be the main mechanism underlying the clinical effects of calcium channel blocking agents. On the other hand, these agents have been reported to elicit unexpected side effects such as headache, flushing, dizziness, peripheral edema, and sexual dysfunction (e.g., impotence and impaired ejaculation) (2-4, 8, 10, 30, 32, 34). These side effects seem to derive not from the drug's effect on the sympathetic vasoconstrictor mechanism, but rather from effects on parasympathetic-or trigeminal-mediated vasodilator mechanisms (2, 4, 6, 9, 23, 25, 33) . However, little is known about the effects of calcium channel blocking agents on parasympathetic-mediated vasodilation. It is well accepted 1) that the innervation of blood vessels in the orofacial area is very similar to the innervation of those that serve the sex organs (1, 24), 2) that oral tissues, such as the lower lip and tongue, are densely innervated by parasympathetic nerves, and 3) that vasodilation occurs reflexly in such tissues via an activation of parasympathetic nerve fibers (12) (13) (14) (15) (16) (17) (18) (19) . With this in mind, we designed the present study to examine whether the calcium channel blocker nifedipine, as well as other antihypertensive agents considered to act via the autonomic nervous system or the smooth muscle of blood vessels, might modulate parasympathetic-mediated vascular responses in orofacial areas in cats (vasodilation in the lower lip and tongue) and to examine the possible mechanisms underlying any inhibitory effect of nifedipine on parasympathetic vasodilation in the lower lip. In these experiments, we chose doses of the various antihypertensive agents that produced similar falls in systemic arterial blood pressure on intravenous injection. In addition, we measured the actual plasma concentrations of nifedipine reached when it was administered by intravenous infusion or sublingually via a commercial preparation of nifedipine (Adalat). METHODS Preparation of animals. Forty-two adult cats, unselected as to sex and of 2.8-4.2 kg body weight, were initially sedated with ketamine hydrochloride (30 mg/kg im) and then anesthetized with a mixture of ␣-chloralose (50 mg/kg iv) and urethan (100 mg/kg iv). These anesthetics were supplemented if and when necessary throughout the experiment. The anesthetized animals were intubated, paralyzed by intravenous injection of pancuronium bromide (Mioblock; Organon, Teknika, Netherlands; 0.4 mg/kg initially, supplemented with 0.2 mg/kg every hour or so after testing the level
doi:10.1152/ajpregu.2000.279.1.r332 pmid:10896897 fatcat:lsz3c6qvkjaeth5cqfjwyxcqym