Lack of Effect of the Adenosine A1 Receptor Agonist, GR79236, on Capsaicin-Induced CGRP Release in Anaesthetized Pigs

Migraine is a common neurological disorder that is associated with an increase in plasma calcitonin gene-related peptide (CGRP) levels. CGRP, a potent vasodilator released from the activated trigeminal sensory nerves, dilates intracranial blood vessels and transmits vascular nociception. Hence, inhibition of trigeminal CGRP release may prevent neurotransmission and, thereby, ameliorate migraine headache. Therefore, the present study in anaesthetized pigs investigates the effects of a selective adenosine A1 receptor agonist, GR79236 (3, 10 and 30 μg/kg, i.v.) on capsaicin-induced carotid haemodynamic changes and on plasma CGRP release. Intracarotid (i.c.) infusion of capsaicin (10 μg/kg/min, i.c.) increased the total carotid blood flow and conductance as well as carotid pulsations, but decreased the difference between arterial and jugular venous oxygen saturations. These responses to capsaicin were dose-dependently attenuated by GR79236. However, the increases in the plasma CGRP concentrations by capsaicin remained essentially unmodified after GR79236 treatment. The above results suggest that GR79236 may have an antimigraine potential due to its postjunctional effects (carotid vasoconstriction) rather than to prejunctional inhibition of trigeminal CGRP release.

Inhibition of baroreflex vagal bradycardia by nasal stimulation in rats

Nasal stimulation provokes hypertension and bradycardia. We report here that such stimulation inhibits baroreflex vagal bradycardia (BVB). In chloralose- and urethan-anesthetized, β-adrenergic receptor-blocked rats, the aortic depressor nerves were cut and electrically stimulated to induce BVB. Nasal application of smoke, warm distilled water, or cold or hot Ringer solution suppressed BVB, but application of warm Ringer solution did not. Smoke-induced inhibition was abolished by trigeminal but not olfactory denervation. Neither suprapontine decerebration nor C3 spinal cord transection affected the inhibition. Bradycardia induced by electrical stimulation of the peripheral cut end of the cervical vagus nerve (VIB) was suppressed by long-lasting smoke application. Intravenous prazosin, a proposed blocker of prejunctional inhibition of acetylcholine release from the vagus terminals, abolished VIB inhibition but attenuated BVB inhibition only slightly. Thus nasal stimulation inhibits BVB, and this inhibition is mediated exclusively by the trigeminal nerve and occurs principally at the pontomedullary level, although the potential exists for contribution of the prejunctional mechanism. The inhibition of BVB might contribute to cardiovascular regulation associated with protection from atmospheric hazards.