The extent to which parasympathetic vasodilator responses, in the submandibular gland of the cat, depend upon release of nitric oxide related (NO chi) or endothelium-derived relaxing factor (EDRF) within the gland has been investigated in anesthetized cats given N omega-nitro-L-arginine methyl ester (L-NAME) which specifically blocks the synthesis of EDRF from arginine. 2. Close intra-arterial infusions of L-NAME (> or = 100 mg kg-1) produced a steady and significant rise in mean aortic pressure together with a steady increase in basal submandibular vascular resistance over the next 20-30 min, which persisted thereafter. 3. In cats pretreated with propranolol, to block beta-adrenoceptor-mediated vasodilatation, salivation and vasodilatation in response to stimulation of the chorda-lingual nerve were reduced but not abolished by L-NAME (> or = 100 mg kg-1, I.A.). Subsequent administration of atropine (> or = 1 mg kg-1 I.V.) completely suppressed the secretory response and virtually eliminated the vascular response. 4. In cats pretreated with atropine (> or = 1.0 mg kg-1 I.V.) administration of L-NAME (> or = 100 mg kg-1 I.A.) effectively suppressed the vasodilator response to chorda-lingual stimulation at 2 Hz continuously, or at 20 Hz for 1 s at 10 s intervals. 5. Administration of L-NAME (> or = 100 mg kg-1 I.A.) effectively suppressed the submandibular vasodilator response to infusions of VIP (10 and 20 ng I.A.) and significantly reduced, but did not abolish that to acetylcholine (100 ng min-1 I.A.). 6. These results provide further support for the view that both acetylcholine and vasoactive intestinal polypeptide-like immunoreactivity (VIP) are released from the postganglionic parasympathetic nerve terminals and produce effects on the blood vessels in submandibular glands of the cat. They also provide evidence for a direct vascular action of acetylcholine, independent of NO chi, but VIP appears to act indirectly via NO chi formation.
