Nitric oxide‐related vasodilator responses to parasympathetic stimulation of the submandibular gland in the cat.

Abstract

SUMMARY1. The extent to which parasympathetic vasodilator responses, in the submandibular gland of the cat, depend upon release of nitric oxide related (NO.) or endothelium-derived relaxing factor (EDRF) within the gland has been investigated in anaesthetized cats given Nw-nitro-L-arginine methyl ester (L-NAME) which specifically blocks the synthesis of EDRF from arginine.2. Close intra-arterial infusions of L-NAME ( > 100 mg kg-') 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 fi-adrenoceptor-mediated vasodilatation, salivation and vasodilatation in response to stimulation of the chorda-lingual nerve were reduced but not abolished by L-NAME () 100 mg kg-', I.A.). Subsequent administration of atropine (. 1 mg kg-1 i.v.) completely suppressed the secretory response and virtually eliminated the vascular response.4. In cats pretreated with atropine ( 1D0 mg kg-1 i.v.) administration of L-NAME () 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 () 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 NOT, but VIP appears to act indirectly via NO. formation.

Nitric oxide in the control of submandibular gland function in the anaesthetized ferret

“…We conclude that activation of the parasympathetic innervation elicits the release of acetylcholine, together with VIP and, probably, PACAP, which together stimulate vasodilatation and secretion of fluid and protein. Acetylcholine can exert actions independent of de novo synthesis of NO, as appears to be the case in the cat submandibular gland (Edwards & Garrett, 1993), whereas VIP, and presumably PACAP, exert their postsynaptic effects on the vasculature and secretory elements by mechanisms which do depend upon the synthesis of NO. In the submandibular gland of the pig NO has been implicated in vasodilatation evoked not only by VIP but also by acetylcholine and, furthermore, NO has been shown to be of importance for the peptide 'wash-out' from the gland as judged by the output of neuropeptide Y and the use of the NO synthase inhibitor NG-nitro-L-arginine (L-NNA; Modin, Weitzberg, Hbkfelt & Lundberg, 1994a;Modin, Weitzberg & Lundberg, 1994b).…”

“…Although PACAP evokes release of salivary protein, it is probably preferentially concerned with the control of blood flow (Tobin, Asztely, Edwards, Ekstrom, Hikanson & Sundler, 1995;Mirfendereski, Tobin, Htkanson & Ekstrom, 1997). In the submandibular gland of the cat the vasodilator response to VIP, but not to acetylcholine, can be abolished by the administration of Nw-nitro-L-arginine methyl ester (L-NAME; Edwards & Garrett, 1993), which blocks the synthesis of nitric oxide (NO) from endogenous arginine (Rees, Palmer, Schulz, Hodson & Moncada, 1990). In this species L-NAME also blocks the enhancement of protein output that occurs in response to stimulation of the parasympathetic innervation in bursts (Buckle, Parker, Bloom & Edwards, 1995), suggesting that this phenomenon is attributable to release of VIP and involves the generation of endogenous NO. In the present study on the ferret, submandibular vascular and secretory function has been investigated by examining the effects of stimulation of the parasympathetic chorda lingual nerve and administration of acetylcholine or the two peptides VIP and PACAP in the presence of L-NAME, while infusing nitroprusside to provide a constant exogenous supply of NO.…”

Modulation of blood flow and tissue perfusion by endothelium‐derived relaxing factor

“…In theory, L-NAME could block smooth muscle muscarinic receptors (probably the M3 subtype), which may directly mediate endothelium-independent vasodilatation through membrane hyperpolarization (Brayden & Bevan, 1985;Brayden & Large, 1986;Ganitkevich & Isenberg, 1990; Neild, Shen & Surprenant, 1990;Edwards & Garrett, 1992). There is nevertheless convincing evidence that the more biologically stable neurotransmitter peptides VIP and substance P can diffuse from adventitial nerves in salivary gland and skeletal muscle, respectively, and mediate vasodilatation by stimulating endothelial receptors (Persson, Hedqvist & Gustafsson, 1991;Edwards & Garrett, 1993). Neuropeptides such as calcitonin gene-related peptide may similarly contribute to mucosal blood flow in the gastrointestinal trace by stimulating EDRF synthesis (Whittle, 1993).…”

Secretory interactions between the sympathetic and parasympathetic innervations of the submandibular gland in the anaesthetized cat

“…At higher frequencies of parasympathetic stimulation, at which the cholinergic drive to protein secretion predominates, that effect is somehow reduced by simultaneous stimulation of the sympathetic innervation. The precise mechanism upon which this inhibition depends has yet to be identified but does not appear to relate to any restriction of the flow of blood through the gland, which is not compromised by this pattern of sympathetic stimulation (20 Hz in bursts; Figs 3 and 4; Edwards & Garrett, 1992, 1993 (Edwards & Titchen, 1990), rat (Asking, 1985) and probably the cat (Proctor, Emmelin & Garrett, 1989). Submandibular peroxidase output followed a similar pattern, except that parasympathetic was less effective than sympathetic stimulation in releasing the enzyme over the whole range of frequencies tested.…”