Endogenous nitric oxide required for an integrative respiratory function in the cat brain

Ling, Liming; Karius, D. R.; Fiscus, Ronald R.; Speck, Dexter F.

doi:10.1152/jn.1992.68.5.1910

Cited by 31 publications

(18 citation statements)

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“…There is also experimental evidence that NO modulates e.g. drinking behaviour (Calapai et al, 1992), nociception (Moore et al, 1991), integrative respiratory function (Ling et al, 1992), and wakefulness (Kapas et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Effect of intracerebroventricular and intravenous administratioi of nitric oxide donors on blood pressure and heart rate in anaesthetized rats

Nurminen

Vapaatalo

1996

British J Pharmacology

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1 The effects of nitric oxide (NO) releasing substances, sodium nitroprusside, 3-morpholino sydnonimine (SIN-1) and a novel oxatriazole derivative, GEA 3162, on blood pressure and heart rate were studied after peripheral or central administration in anaesthetized normotensive Wistar rats. 2 Given as cumulative intravenous injections, both nitroprusside and GEA 3162 (24-188 nmol kg-') induced short-lasting and dose-dependent decreases in mean arterial pressure, while SIN-1 decreased blood pressure only slightly even after larger doses (94-3000 nmol kg-'). Heart rate increased concomitantly with the hypotensive effect of the NO-releasing substances.3 Cumulative intracerebroventricular administration of GEA 3162 (24-188 nmol kg-') induced a dose-dependent hypotension with slight but insignificant increases in heart rate. In contrast, intracerebroventricular nitroprusside induced little change in blood pressure, while a large dose of SIN-1 (3000 nmol kg-', i.c.v.) slightly increased mean arterial pressure. However, intracerebroventricular nitroprusside and SIN-1 increased heart rate at doses that did not significantly affect blood pressure.4 To determine whether the cardiovascular effects of GEA 3162 were attributable to an elevation of cyclic GMP levels, pretreatments with methylene blue, a putative guanylate cyclase inhibitor, were performed. This substance failed to attenuate the cardiovascular effects of peripherally or centrally administered GEA 3162, suggesting that the effects were independent of guanylate cyclase. 5 In conclusion, the centrally administered NO-donor, GEA 3162, induced a dose-dependent hypotensive response without significant changes in heart rate. Furthermore, intracerebroventricular injections of nitroprusside and SIN-1 increased heart rate without affecting blood pressure. These results suggest that NO released by these drugs may affect central mechanisms involved in cardiovascular regulation independently of cyclic GMP.

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Section: Introductionmentioning

confidence: 99%

Effect of intracerebroventricular and intravenous administratioi of nitric oxide donors on blood pressure and heart rate in anaesthetized rats

Nurminen

Vapaatalo

1996

British J Pharmacology

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“…In accordance with this model, postsynaptic activation of NMDA receptors and opening of calcium channels associated with these receptors produce an increased level of intracellular Ca 2+ that, via calmodulin, activates NO synthase. Microinjections of an inhibitor of NO synthase into the region of pontine respiratory neuronal grouping of adult decerebrated and decerebellated cats prolong inspiration (in a test without swelling the lungs) [10]. This shows that the effect of activation of the NMDA receptors in the framework of a pontine pneumotaxic function is mediated by NO.…”

Section: Discussionmentioning

confidence: 86%

“…At the same time, NO is known to be involved in the control of neuronal activity in the ventrolateral region of the medulla (VLM) [6,7 ], where the bulbar respiratory generator is localized [8,9]. In cats, endogenous NO is shown to be involved in functioning 334 0090-2977/97/29060334518.00 01998 Plenum Publishing Corporation of the pontine pneumotaxic center [10]. The NO role in pathogenesis of hypoxia and ischemia of the brain attracts special attention.…”

Section: Introductionmentioning

confidence: 99%

Effect of nitric oxide on the respiratory activity generated under hypoxic conditions by medullo-spinal preparations from early postnatal rats

1997

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Experiments on superfused in situ semi-isolated medullo-spinai preparations (SIMSP) of 3-to 4-day-oid rats were carried out to study the effects of a blocker of nitric oxide synthase (NO synthase), methyl ester of NX;-nitro-L-arginine (MENA), and an exogenic NO donor, nitroglycerin, on the respiratory activity. Inspiratory discharges (ID) were recorded from the phrenic nerve under superfusion of SIMSP with a standard saline and a solution saturated with anoxic isocapnic gas mixture. Under normal conditions, 3-rain-long applications of 1.0/tM MENA evoked no significant changes in the parameters of inspiratory activity; yet 10.0/~M of this blocker evoked a significant drop in the amplitude and an increase in the ID frequency. Three-rain-long applications of 1.0 ,uM nitroglycerin significantly decreased the ID frequency and somewhat increased their amplitude and integral intensity. Higher dc6es of nitroglycerin (I0.0 ,uM) significantly incmd the amplitude and integral intensity of ID and in a lesser extent lowered their frequency. Under conditions of 3-rain-long hypoxia, 10-rain-long preliminary superfusion of SIMSP with the 1.0/~M MENA-containing saline resulted in no significant changes of respiratory activity, as compared with the hypoxia effect in the norm. Applied before the hypoxic test. 10/~M MENA resulted in significant decreases in the amplitude and integral intensity of ID; concurrently their frequency became higher, as compared with the r~tive parameters measured at hypoxic testing of the intact preparations. Ten-rain-long superfnsion with 1.0 /xM nitroglycerin-containing soiution at subsequent hypoxic testing significantly increased the amplitude and integral intensity of ID and decreased their frequency; these shifts deveioped during the first half of exposure to the hypoxic solution. Increased (to 10 btM) nitroglycerin concentration resulted in le..m intensive shifts in the ID frequency within the first half of a hypoxic episode. In a part of the tests, the second half of exposure of SIMSP to the hypoxic solution was characterized by the appearance of low-amplitude short ID against the background of supped eupnea-like respiratory activity; we qualified such discharges as gasping discharges. The experimental data confirm the involvement of NO in the central regulation of the frequency and amplitude parameters of inspiratory activity generated by SIMSP of early postuatal rats both under normoxic and hypoxic conditions. The role NO plays under hypoxic conditions in modifications of parameters of respiratory activity and in modulation of the functional levels of the liulbar respiratory generator is discussed.

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“…It has been demonstrated that NO enhances the excitability and spontaneous discharge rates of neurons in the NTS (27) and may act as a retrograde messenger in an L-glutamate-releasing positive feedback system, also in the NTS, involved in the increase of ventilation during hypoxia (24). NO has an excitatory effect on the discharge rates of neurons in the pontine respiratory group, whereas L-NNA produces a disruption of the pneumotaxic mechanism (28).…”

Section: Discussionmentioning

confidence: 99%

Participation of nitric oxide in the nucleus isthmi in CO2-drive to breathing in toads

Gargaglioni

Branco

1999

Braz J Med Biol Res

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The nucleus isthmi (NI) is a mesencephalic structure of the amphibian brain. It has been reported that NI plays an important role in integration of CO 2 chemoreceptor information and glutamate is probably involved in this function. However, very little is known about the mechanisms involved. Recently, it has been shown that nitric oxide synthase (NOS) is expressed in the brain of the frog. Thus the gas nitric oxide (NO) may be involved in different functions in the brain of amphibians and may act as a neurotransmitter or neuromodulator. We tested the hypothesis that NO plays a role in CO 2 -drive to breathing, specifically in the NI comparing pulmonary ventilation, breathing frequency and tidal volume, after microinjecting 100 nmol/0.5 µl of L-NAME (a nonselective NO synthase inhibitor) into the NI of toads (Bufo paracnemis) exposed to normocapnia and hypercapnia. Control animals received microinjections of vehicle of the same volume. Under normocapnia no significant changes were observed between control and L-NAME-treated toads. Hypercapnia caused a significant (P<0.01) increase in ventilation only after intracerebral microinjection of L-NAME. Exposure to hypercapnia caused a significant increase in breathing frequency both in control and L-NAME-treated toads (P<0.01 for the control group and P<0.001 for the L-NAME group). The tidal volume of the L-NAME group tended to be higher than in the control group under hypercapnia, but the increase was not statistically significant. The data indicate that NO in the NI has an inhibitory effect only when the respiratory drive is high (hypercapnia), probably acting on tidal volume. The observations reported in the present investigation, together with other studies on the presence of NOS in amphibians, indicate a considerable degree of phylogenetic conservation of the NO pathway amongst vertebrates.

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Endogenous nitric oxide required for an integrative respiratory function in the cat brain

Cited by 31 publications

References 0 publications

Effect of intracerebroventricular and intravenous administratioi of nitric oxide donors on blood pressure and heart rate in anaesthetized rats

Effect of intracerebroventricular and intravenous administratioi of nitric oxide donors on blood pressure and heart rate in anaesthetized rats

Effect of nitric oxide on the respiratory activity generated under hypoxic conditions by medullo-spinal preparations from early postnatal rats

Participation of nitric oxide in the nucleus isthmi in CO2-drive to breathing in toads

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