MUSCARINIC MODULATION OF THE VASODILATORY EFFECTS OF VASOACTIVE-INTESTINAL-PEPTIDE AT THE RAT-THYROID GLAND

In the thyroid gland, vasoactive intestinal peptide (VIP) and acetylcholine (ACh) are found in nerve fibers associated with secretory cells and blood vessels. We have, therefore, initiated studies to explore the actions of and interactions between cholinergic agents and VIP in the regulation of thyroid vascular conductance (VC). Thyroid and other organ blood flows were measured using radiolabelled (Ce-141) microspheres injected directly into the left cardiac ventricle of anesthetized male rats. They mean systemic arterial pressure was monitored and used in the calculation of organ VC (blood flow/arterial pressure). Plasma TSH, T3, and T4 levels before and after infusions were measured by RIA. The acute administration of ACh (3 x 10(-8) mol/100 g BW) over 4 min increased thyroid VC, whereas nicotine (10(-7) mol /100 g BW) had no such effect. Circulating TSH and thyroid-hormone levels following ACh or nicotine were not different from those in vehicle-treated animals at 20 min or 2 h after infusion. This observation suggested that ACh acts through muscarinic receptors at the thyroid gland to increase VC. In order to extend these observations and to evaluate whether VIP might exert any of its thyroidal effects on VC via muscarinic receptors, we assessed the effects of ACh, methacholine chloride (MCC), and VIP in the presence and absence of the muscarinic receptor blocker atropine. Rats were treated intravenously with saline or atropine (3 mg/kg) 20 min before intravenous infusions of vehicle, ACh (3 x 10(-8) mol/100 g BW), MCC (5 x 10(-9) mol/100 g BW), or VIP (10(-11) mol/100 g BW). Muscarinic blockade prevented the ACh-induced rise in thyroid VC, whereas the vasodilatory effect of VIP was greater if the rats were pretreated with atropine. These results are consistent with the hypothesis that VIP and ACh exert their effects at the thyroid and through independent mechanisms. Furthermore, there appears to be an antagonistic interaction between cholinergic agents and VIP in the regulation of thyroid VC.