Nitric oxide synthase in the autonomic and sensory ganglia innervating the submandibular salivary gland

Soinila, Seppo; Vanhatalo, Sampsa; Lumme, Aki; Back, Nathan; Soinila, Jouni

doi:10.1002/(sici)1097-0029(19960901)35:1<32::aid-jemt4>3.0.co;2-u

Cited by 24 publications

(8 citation statements)

References 51 publications

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“…NO is a non‐adrenergic and non‐cholinergic neurotransmitter as well as a potent vasodilator known to play a key role in salivary gland function and secretion of saliva 7 . nNOS is expressed in nerve fibers surrounding the acini of the parotid and submandibular salivary glands in many mammalian species as well as surrounding acini in human labial salivary glands 19–23 . Notably, the presence of NOS in human and rodent acinar cells has been demonstrated by functional studies measuring NO synthesis and by determining NOS expression 7 .…”

Section: Discussionmentioning

confidence: 99%

Effects of Diabetes on Salivary Gland Protein Expression of Tetrahydrobiopterin and Nitric Oxide Synthesis and Function

Stewart

Obi

Epane

et al. 2016

Journal of Periodontology

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Background Xerostomia is defined as dry mouth resulting from a change in the amount and/or composition of saliva and often a major oral health complication associated with diabetes. Studies have shown that xerostomia is more common in females in the onset of diabetes. Evidence suggests that nitric oxide (NO) plays a critical role in healthy salivary gland function. However, the specific mechanisms by which NO regulates salivary gland function at the onset of diabetes have yet to be determined. This study had two aims: 1. To determine whether protein expression and/or dimerization of NO synthase enzymes (nNOS, eNOS) are altered in the onset of diabetic xerostomia and 2. To determine whether the changes in nNOS/eNOS protein expression/dimerization are correlated with changes in NO cofactor, tetrahydrobiopterin (BH4) biosynthetic enzymes (GTP Cyclohydrolase-1, Dihydrofolate reductase). Methods Functional and western blot studies were performed in streptozotocin-induced diabetic (type 1 diabetes) and control Sprague Dawley female rats using standardized protocols. Confirmation of xerostomia was determined by increased water intake and decreased salivary flow rate. Results In diabetic female rats, salivary hypofunction is correlated with decreased submandibular and parotid gland sizes. Furthermore, our results show a decrease in NOS and BH4 biosynthetic enzyme in submandibular glands. Conclusion Our results indicate that a decrease in submandibular NO-BH4 protein expression may provide insight pertaining to mechanisms for the development of hyposalivation in diabetes-induced xerostomia. Furthermore, understanding the role of NO-BH4 pathway may give insight to possible treatment options for the diabetic patient experiencing xerostomia.

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Section: Discussionmentioning

confidence: 99%

Effects of Diabetes on Salivary Gland Protein Expression of Tetrahydrobiopterin and Nitric Oxide Synthesis and Function

Stewart

Obi

Epane

et al. 2016

Journal of Periodontology

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“…First, because we infused the drugs intravenously, we cannot specify the site(s) of NOS inhibition that led to the rise in renal SNA. In this regard, afferent, central, or efferent neural mechanisms could all be involved (8,9,21,28,38,39,45,48,50). Second, although SAD interrupts baroreceptor influence, chronic SAD may also lead to alterations in central neural transmission within brainstem nuclei, such as the nucleus tractus solitarius, which could modulate cardiovascular responses (12).…”

Section: Discussionmentioning

confidence: 99%

l-NAME- and ADMA-induced sympathetic neural activation in conscious rats

Augustyniak

Victor²,

Morgan³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Although studies in anesthetized, sino-aortic denervated animals indicate that inhibition of central nitric oxide (NO) causes an excitatory influence on efferent sympathetic nerve activity (SNA) that is normally offset by baroreflex activation, studies in conscious animals have not provided clear-cut evidence for a sympathoexcitatory effect of N(omega)-nitro-l-arginine methyl ester (L-NAME) or the endogenous circulating NO synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA). Thus our goals were to 1) use surgical sino-aortic denervation to test for a sympathoexcititatory effect of intravenous l-NAME in conscious rats, and 2) to determine whether SNA responses to intravenous L-NAME can be extrapolated directly to intravenous ADMA. We recorded mean arterial blood pressure and renal SNA in both intact and sino-aortic-denervated conscious rats during 3 h of continuous intravenous infusion with either L-NAME or ADMA. When we eliminated the confounding influence of the sino-aortic baroreceptors, L-NAME produced a progressive increase in SNA with the peak response exceeding the baseline level of nerve firing by 150%. The same type of frank sympathetic activation was observed with intravenous ADMA. Taken together, these data offer straightforward evidence for l-NAME, as well as ADMA-induced sympathetic activation with direct recordings of SNA in conscious animals. These data confirm and extend the concept that circulating endogenous NOS inhibitors can constitute an excitatory signal to SNA.

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“…Finally, endothelial cells are assumed to be the source of NO acting on vascular smooth muscle, but NO synthase‐immunoreactive nerves have been described in rat salivary glands (Soinila et al 1996; Alm et al 1997; Takai et al 1999). Further, parasympathetic denervation caused an almost complete loss of NO synthase immunoreactivity in the rat parotid gland (Alm et al 1997).…”

Section: Discussionmentioning

confidence: 99%

The influence of gender on parasympathetic vasodilatation in the submandibular gland of the rat

Anderson¹,

Martin²,

Phillips³

et al. 2006

Experimental Physiology

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Parasympathetic vasodilatation in the rat submandibular gland is mediated by nitric oxide-dependent and -independent mechanisms (prostacyclin and endothelium-derived hyperpolarizing factor (EDHF)). The purpose of this study was to determine the influence of gender on the relative contributions of each pathway to nerve-stimulated vasodilatation. Absolute increases in perfusion (laser Doppler flowmetry) were similar in male and female rats (in arbitrary perfusion units: 6159 ± 4530 and 5601 ± 3877 at 2 Hz; 15645 ± 6830 and 14848 ± 6118 at 5 Hz; and 22418 ± 7660 and 18878 ± 5864 at 10 Hz). However, expressed as a percentage increase above resting values, stimulated perfusion was higher in males than in females (P < 0.05). In males both N ω -nitro-L-arginine methyl ester (L-NAME) and indomethacin partly blocked parasympathetic vasodilatation at all frequencies tested (P < 0.05). In female rats significant reductions in nerve-stimulated perfusion were observed only at 2 and 5 Hz, but the effects of L-NAME were greater than in males (−64 compared with −45% at 2 Hz and −45 compared with −33% at 5 Hz, P < 0.05). Indomethacin by itself had no apparent effect in females. The combined effects of L-NAME and indomethacin were dependent on the order of administration and on gender. Following L-NAME, indomethacin had no further effect in males or females. L-NAME reduced indomethacin-resistant vasodilatation in males and females, but the added effect of indomethacin was more pronounced in males. Finally, atropine-resistant vasodilatation was partly blocked by L-NAME, and the remaining vasodilatation was abolished by spantide I (substance P receptor antagonist). We conclude that NO, products of cyclo-oxygenase activity and EDHF all play a role in parasympathetic vasodilatation, but that NO and EDHF are the major endothelium-derived vasodilators in the rat submandibular gland. In addition, when other pathways are blocked EDHF makes a greater contribution in females. Lastly, both vasoactive intestinal peptide and substance P contribute to the atropine-resistant vasodilatation.

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Nitric oxide synthase in the autonomic and sensory ganglia innervating the submandibular salivary gland

Cited by 24 publications

References 51 publications

Effects of Diabetes on Salivary Gland Protein Expression of Tetrahydrobiopterin and Nitric Oxide Synthesis and Function

Effects of Diabetes on Salivary Gland Protein Expression of Tetrahydrobiopterin and Nitric Oxide Synthesis and Function

l-NAME- and ADMA-induced sympathetic neural activation in conscious rats

The influence of gender on parasympathetic vasodilatation in the submandibular gland of the rat

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