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Biomedical subjects

L E Gustafsson

Publications and source records attributed to L E Gustafsson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Contribution from upper and lower airways to exhaled endogenous nitric oxide in humans.

Endogenous nitric oxide (NO) is thought to regulate many biological functions, including pulmonary circulation and bronchomotion, and it has been found in exhaled air. Our aim was to study the excretion of NO in different parts of the respiratory system. Exhaled concentrations of NO were measured by chemiluminescence in chronic tracheostomy outpatients (group 1), in patients admitted for minor abdominal surgery (group 2), and in patients with acute respiratory failure (ARF) during mechanical ventilation (group 3). In awake volunteers (group 4), 0.57 L/min gas was aspirated through the nasal cavity into the chemiluminescence device. In group 1 (tracheostomy, n = 5) we detected 16 +/- 2 (mean +/- s.e. mean) parts per billion (ppb) NO when exhaling through the mouth, and a lower (P < 0.05) value of 4.6 +/- 0.8 ppb NO when exhaling through the tracheostomy. Before anaesthesia, group 2 (n = 11) exhibited 18 +/- 2.4 ppb NO in orally exhaled gas, increasing considerably during exhalation through the nose. Upon endotracheal intubation exhaled NO concentration dropped to 1.3 +/- 0.2 ppb (P < 0.05). In group 3 (ARF, n = 7) tracheal NO concentrations were 0.8 +/- 0.2 ppb. In group 4 (volunteers, n = 6) 394 +/- 23 ppb NO was recorded in air from the nasal cavity. In both healthy subjects and patients with respiratory failure a significant NO excretion occurs in the lower airways and lungs. The upper airways, especially the nose, contribute the largest amount of NO (> 90%) to exhaled air. The physiological implications of an upper airway source of NO remain to be defined.

Adolescent↗
PubMed1995

The promotion of patent airways and inhibition of antigen-induced bronchial obstruction by endogenous nitric oxide.

1. The aim of the present study was to investigate the role of nitric oxide (NO), histamine and leukotrienes in bronchial obstruction. For this, guinea-pigs immunised against ovalbumin were studied under anaesthesia during challenge with antigen or agonists. 2. Challenge with nebulised antigen (0.1-1 mg) elicited dose-dependent increases in insufflation pressure which were abolished by combined administration of histamine and leukotriene antagonists. 3. Challenge with nebulised antigen (0.1-1 mg) also elicited dose-dependent increases in the concentration of endogenous nitric oxide in the exhaled air. After an initial peak, exhaled NO concentrations returned to pre-challenge levels. 4. The increase in insufflation pressure and in exhaled NO caused by ovalbumin challenge was inhibited by combined administration of histamine and leukotriene antagonists. 5. In non-immunised guinea-pigs, challenge of the airways with nebulised histamine (10-1000 nmol) or leukotriene C4 (LTC4, 30-300 pmol) elicited dose-dependent increases in insufflation pressure and in concentrations of endogenous NO in exhaled air. 6. The increase in exhaled NO correlated with the increase in insufflation pressure in response to ovalbumin, histamine and LTC4. An inhibitor of endogenous NO synthesis, N omega-nitro-L-arginine methylester (L-NAME, 30 mg kg-1 i.v.) abolished NO exhalation, and markedly augmented the airway responses to ovalbumin, histamine, or LTC4. 7. The potentiation by L-NAME of the increase in insufflation pressure in response to ovalbumin or histamine was prevented by exogenous NO (20 p.p.m.) in the inhaled air. 8. The results indicate that endogenous NO has an inhibitory effect on bronchial obstruction. Increased NO release during allergen challenge is likely to be due to actions of histamine and leukotrienes.

Airway Obstruction↗
PubMed1994

Ca(2+)-dependent and Ca(2+)-independent exhaled nitric oxide, presence in germ-free animals, and inhibition by arginine analogues.

Nitric oxide (NO) was detected by chemiluminescence in exhaled air from awake humans, anaesthetized rabbits, guinea pigs, germ-free rats and conventional rats. Rabbits exhibited the highest concentrations, followed by guinea pigs, humans and rats. There was no significant difference between germ-free rats and control rats. The authenticity of NO was confirmed in cold-trap experiments. Intravenous administration of inhibitors of NO synthase (0.01-300 mg kg-1) to guinea pigs dose dependently reduced NO concentrations in exhaled air with the following potency order: L-N omega-nitro-arginine-methylester > asymmetric NG,NG-dimethyl-L-arginine-dihydrochloride = L-NG-mono-methyl -arginine = L-N5- (1-iminoethyl)-ornithine = aminoguanidine > L-canavanine. The effect of the NO synthase inhibitors was partly or fully reversed by L-arginine (1 g kg-1 i.v.), and L-arginine per se induced a significant increment of NO in exhaled air. In rats, L-N omega-nitro-arginine-methylester was considerably less potent than in guinea pigs. The concentration of NO in exhaled air increased 3-fold when changing from in situ blood auto-perfusion of rabbit lungs to in situ perfusion with saline medium. Addition of L-N omega-nitro-arginine-methylester to the saline perfusion medium evoked a reduction of NO concentrations in the air from the ventilated perfused lungs. Perfusion of lungs with Ca(2+)-free medium induced significant decrements in NO concentrations in exhaled air, an effect partly reversed upon reintroducing Ca2+ into the medium. In conclusion, NO was detected in exhaled air from humans and animals by chemiluminescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Ethanol causes decrements in airway excretion of endogenous nitric oxide in humans.

Ethanol has previously been demonstrated to inhibit excretion of endogenous nitric oxide (NO) in exhaled air from experimental animals. The aim of the present study was to elucidate if this effect also occurs in human subjects. Healthy volunteers ingested ethanol (0.25 and 1 g kg-1, 20% in orange juice). Nitric oxide in exhaled air was determined by chemiluminescence. Single-breath analysis of exhaled air was performed and peak values of NO and end expiratory levels of NO and CO2 were determined. Ethanol induced dose-dependent decrements in exhaled nitric oxide. Thus, peak values for nitric oxide in exhaled air, in the first exhalation after breath-holding for 30 s, decreased to 56 +/- 10 and 37 +/- 12% of control 60 min after ingestion of ethanol at 0.25 and 1 g kg-1, respectively. Rinsing the oral cavity (including gargling) for 15 min with 20% ethanol in juice did not significantly influence NO in exhaled air. Heart rate blood pressure and end expiratory levels of CO2 were not significantly affected by ethanol ingestion. In conclusion, ethanol decreases levels of nitric oxide in exhaled air in humans, likely by inhibition of airway formation of nitric oxide. The results might be of importance in understanding effects of ethanol and other hydrocarbons.

Adult↗
PubMed1994

Nitric oxide is present in exhaled breath in humans: direct GC-MS confirmation.

The physiological role of nitric oxide (NO) is being investigated in many experimental and clinical settings. There is considerable evidence that NO is involved in the regulation of lung vascular function. In addition there are many studies reporting the beneficial effect of NO inhalation. NO formed from L-Arginine has been detected in exhaled breath using indirect mass spectrometry and chemiluminescence. Both methods provided good evidence for the presence of NO in breath samples but were not unequivocal. We therefore developed a method using gas-chromatography-mass spectrometry which allowed us to measure trace levels of NO in air and breath. Eight healthy volunteers supplied numerous breath samples for analysis. A clear peak for nitric oxide was observed in seven volunteers. The mean level was 13ppb (n = 7, range < 2 to 19ppb). This data is in good agreement with our previous data and unequivocally confirms the presence of nitric oxide in human breath.

Female↗
PubMed1994

Direct demonstration of NO formation in vivo from organic nitrites and nitrates, and correlation to effects on blood pressure and to in vitro effects.

Previous studies, utilizing nitric oxide synthase inhibitors and nitric oxide application, indicate that nitric oxide has the capacity to modulate contractile responses in pulmonary vessels. In the present study, in vitro effects of organic nitrates/nitrites were compared with their in vivo ability to generate nitric oxide and their effects on blood pressure. Glyceryl trinitrate, ethyl nitrite, isobutyl nitrate, isobutyl nitrite, isoamyl nitrite and butyl nitrite inhibited contractions in response to nerve stimulation in guinea pig pulmonary artery and vas deferens. Glyceryl trinitrate (also known as nitroglycerin) was the most potent and isobutyl nitrate the least potent substance with this action (IC50 4.5 +/- 0.2 x 10(-10) and 1.1 +/- 0.1 x 10(-5) M, respectively). Contractile responses to noradrenaline were inhibited, whereas noradrenaline release was unaffected by organonitrates/nitrites, indicating a post-junctional inhibitory effect. When infused intravenously to anaesthetized rabbits glyceryl trinitrate, ethyl nitrite and isobutyl nitrate generated dose-dependent increments of nitric oxide in exhaled air and dose-dependent decrements in systemic blood pressure. Significant correlations were obtained between in vivo NO generation and effects on blood pressure, as well as between NO generation in vivo and the in vitro activity of the organic nitrites and organic nitrates. In conclusion, organic nitrites and organic nitrates can modulate adrenergic neuroeffector transmission in guinea pig pulmonary artery and vas deferens, and produce detectable concentrations of nitric oxide in exhaled air in vivo, in the rabbit. The observations give direct in vivo evidence that organic nitrites and nitrates generate NO, and strongly support them exerting their action via NO formation.

Animals↗
PubMed1994

Single-breath nitric oxide measurements in asthmatic patients and smokers.

Exhaled nitric oxide (NO) concentrations were measured in asthmatic outpatients and in non-smoking and smoking healthy controls. In single exhalations, NO showed a peak suggestive of airway origin in both controls and asthmatic patients. The peak NO concentration was higher in asthmatic patients and lower in smokers than in non-smoking controls (p < 0.05). The findings support a role for NO in the host defence response in asthma and suggest that NO measurements can discriminate between different types of lung disorders.

Adult↗
PubMed1994

Tumour necrosis factor-alpha and nitric oxide, determined as nitrite, in malignant pleural effusion.

Pleurodesis treatment is often used to stop chronic pleural effusion in malignant pleurisy. During the treatment a strong intrapleural inflammation is induced leading to the cessation of exudation. In this study the concentrations of tumour necrosis factor (TNF-alpha) and nitric oxide (NO), determined as its immediate metabolite nitrite, were measured in pleural fluid, in order to investigate if they were involved in pleural inflammation and pleural fluid exudation. Determinations were made in pleural fluid from patients with malignant pleural effusion, before and during therapeutic quinacrine-induced pleural inflammation. TNF-alpha concentrations were measured by ELISA-technique and NO/nitrite by chemiluminescence. TNF-alpha increased significantly after quinacrine instillation. NO/nitrite was initially present at the same concentrations as found in normal serum, and increased significantly during treatment. Concentrations of TNF-alpha correlate with the amount of pleural fluid production after quinacrine instillation, in that a higher level of TNF-alpha is associated with more pleural fluid production. No correlation was found between TNF-alpha and NO/nitrite, whereas a weak but significant correlation was found between NO/nitrite and concentrations of another cytokine, interleukin-1 beta (IL-1 beta). The results suggest that TNF-alpha might contribute to pleural fluid exudation and that TNF-alpha and NO are of importance in induced pleural inflammation. IL-1 beta might be one of several stimuli for NO formation in this setting.

Adult↗
PubMed1994

Neurogenic vasodilation in rabbit hindlimb mediated by tachykinins and nitric oxide.

We investigated the role of nitric oxide (NO) in the mediation of nerve stimulation-induced vasodilation in skeletal muscle. Hindlimb blood flow and vascular resistance were measured in pentobarbital-anesthetized, paralyzed, and guanethidine-treated rabbits. Centrifugal electrical stimulation of the sciatic nerve bundle induced reproducible, frequency-, voltage-, and pulse duration-dependent decrements in vascular resistance. The tachykinin antagonist CP-96,345 (1 mg/kg intravenously, i.v.) attenuated the vasodilation induced by intraarterially (i.a.) administered substance P but not by adenosine. Furthermore, CP-96,345 attenuated the decrease in vascular resistance in response to nerve stimulation, from 22.9 +/- 3.2 to 4.5 +/- 4.1% of control resting resistance (p < 0.005), without affecting basal vascular resistance. An inhibitor of NO formation, N omega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg i.v.), increased vascular resistance from 6.1 +/- 0.5 to 9.1 +/- 1.2 resistance units (p < 0.05) and significantly attenuated the vascular response to i.a. administered substance P but not adenosine. Finally, nerve stimulation-induced reduction in vascular resistance was attenuated by L-NAME, from 22.6 +/- 2.7 to 7.0 +/- 1.0% of control (p < 0.001). These findings suggest that tachykinins and NO are involved in mediation of vasodilation in response to the present type of nerve stimulation. The data are consistent with the hypothesis that NO is produced subsequent to neural release of tachykinin-type transmitter(s).

Animals↗
PubMed1994

Detection of nitric oxide in exhaled air during administration of nitroglycerin in vivo.

1. Direct evidence for nitric oxide (NO) formation from nitroglycerin (GTN) was obtained by measurements of NO concentrations in exhaled air in artificially-ventilated, pentobarbitone-anaesthetized rabbits. 2. The concentration of endogenously formed NO was 23 +/- 5 parts per billion (p.p.b.). Infusions of GTN (1-100 micrograms kg-1 min-1, i.v.) induced dose-dependent and biphasic increments in exhaled NO and concomitant reductions in systemic blood pressure. 3. Tolerance to the blood pressure reduction developed in parallel with a decrease in GTN-induced exhaled NO, a pattern which was unaffected by administration of N omega-nitro-L-arginine methyl ester (L-NAME, 30 mg kg-1), L-cysteine (200 mg kg-1), N-acetylcysteine (200 mg kg-1) or glutathione (200 mg kg-1). 4. Intravenous infusions of adenosine (0.7 mg ml-1, 250 microliters kg-1 min-1) and GTN (1 mg ml-1, 250 microliters kg-1 min-1) elicited similar decrements in pulmonary vascular resistance. GTN elicited a substantial increase in exhaled NO (50 +/- 10 p.p.b.) whereas adenosine evoked a markedly smaller increase (7 +/- 1 p.p.b.). L-NAME (30 mg kg-1, i.v.) abolished NO in exhaled air, and evoked an increase in pulmonary vascular resistance from 116 +/- 19 to 147 +/- 9 pulmonary vascular resistance units. After L-NAME the change in pulmonary vascular resistance induced by adenosine or GTN was increased to a similar degree. However, while the increase in exhaled NO induced by nitroglycerin was unaffected, the response to adenosine was abolished. 5. The present data demonstrate that NO is formed from GTN in vivo. Furthermore, thiol availability,or nitric oxide synthase activity are not limiting factors in the conversion of nitroglycerin to NO in vivo.Finally, pulmonary haemodynamic changes per se do not explain the observed increase in NO upon nitroglycerin infusion.

Acetylcysteine↗
PubMed1994

Smooth muscle relaxing effects of NO, nitrosothiols and a nerve-induced relaxing factor released in guinea-pig colon.

1. The aim of the present study was to compare the biological activity of S-nitroso-L-cysteine (CYSNO), S-nitrosoglutathione (GSNO), S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and hydroxylamine to that of nitric oxide (NO) and a vascular relaxing factor released by nerve stimulation in the guinea-pig intestine. The biological activity was examined in a bioassay system with guinea-pig colon as donor tissue and a series of spiral strips of rabbit aorta without endothelium as detector tissues. 2. Electrical stimulation of the guinea-pig colon released a vascular relaxing factor. The half-life of the relaxing factor down the bioassay cascade was the same as exogenously applied NO. N omega-nitro-L-arginine (L-NOARG) inhibited the release of bioactivity. 3. The relaxations of the assay tissues caused by exogenous CYSNO also declined during the passage down the cascade. However, in the presence of L-cysteine (10(-5) M) the half-life of CYSNO increased and there was no significant breakdown through the cascade. In contrast, the half-life of applied NO and the vascular relaxing factor released by nerve stimulation was unaffected by the presence of L-cysteine. 4. Exogenously applied GSNO (20-50 nM), SNAP (2-4 nM) and hydroxylamine (300-600 nM) caused relaxations that did not decline during the passage down the cascade. 5. In summary, the relaxation of the bioassay tissues during nerve stimulation was indistinguishable from the relaxation induced by NO, whereas relaxations induced by CYSNO, GSNO, SNAP and hydroxylamine showed different pharmacological profiles. The released bioactivity is thus likely to be NO itself.

Animals↗
PubMed1994

Modulation of neuroeffector transmission in guinea-pig pulmonary artery and vas deferens by exogenous nitric oxide.

Blockade of nitric oxide (NO) synthesis enhances contractile responses to transmural nerve stimulation in guinea-pig pulmonary artery, indicating neuromodulation by endogenous nitric oxide. In the present study, neuromodulatory effects of exogenous NO were examined in guinea-pig pulmonary artery and vas deferens. Application of NO as acid nitrite, to the guinea-pig pulmonary artery, inhibited the contractile response to transmural nerve stimulation as well as contractions to exogenous noradrenaline. The inhibition occurred in a dose-dependent manner. Acid nitrite did not affect stimulation-induced release of [3H]noradrenaline in guinea-pig pulmonary artery. In the guinea-pig vas deferens, contractile 'twitch' responses to brief (25 pulses) transmural nerve stimulation and stimulation-induced release of [3H]noradrenaline was unaffected by acid nitrite. However, 'twitch' responses to prolonged stimulation were inhibited by acid nitrite, and tonic 'hump' responses were either enhanced or unaffected by acid nitrite. In conclusion, exogenous nitric oxide exerted an inhibition of adrenergic neurotransmission post-junctionally in guinea-pig pulmonary artery. In guinea-pig vas deferens, exogenous nitric oxide affected adrenergic and/or non-adrenergic noncholinergic neurotransmission in a complex fashion, however without alteration in noradrenaline release. The data support a role for NO in modulation of neuroeffector transmission, especially by modulation of effector sensitivity, whereas modulation of noradrenaline release seems an unlikely role for NO in these and similar peripheral tissues.

Animals↗
PubMed1994

Oxygen or low concentrations of nitric oxide reverse pulmonary vasoconstriction induced by nitric oxide synthesis inhibition in rabbits.

The objective of this study was to investigate the role of nitric oxide and oxygen in the regulation of pulmonary vascular resistance, especially by means of substitution with nitric oxide after inhibition of endogenous nitric oxide formation. In artificially ventilated open-chest rabbits pulmonary vascular resistance at normoxic ventilation (FIO2 = 21%) was 56 +/- 6 cmH2O ml-1 min-1 1000-1 (mRUL). N omega-nitro-L-arginine methyl ester (L-NAME, 30 mg kg-1), an inhibitor of NO synthase, increased pulmonary vascular resistance to 122 +/- 17 mRUL at normoxic ventilation. In response to L-NAME there was also an increase in mean arterial blood pressure. Exogenous nitric oxide (0.014-9 p.p.m. in the inhaled air) dose-dependently and reversibly counteracted the effect of L-NAME on pulmonary vascular resistance at normoxic ventilation, without affecting systemic blood pressure. In addition, the L-NAME-induced vasoconstriction was critically dependent on oxygen. Thus, during hypoxic ventilation (FIO2 = 10%) the pulmonary vascular resistance was increased approximately four-fold by the presence of L-NAME (30 mg kg-1), and increments in FIO2 (21-100%) dose-dependently and reversibly counteracted the effect of L-NAME on pulmonary vascular resistance. Taken together these findings demonstrate that inhalation of low doses of NO may act as a replacement when endogenous NO synthesis is inhibited, and that pulmonary vasoconstriction induced by NO synthesis inhibition is likely to be the result of interference with oxygen-dependent regulatory mechanisms. Endogenous NO co-operates with oxygen to evoke a vasodilator component of the pulmonary hypoxic pressor response, balancing a hitherto unknown constrictor mechanism.

Administration, Inhalation↗
PubMed1994

Nitric oxide-like activity in guinea pig colon as determined by effector responses, bioassay and chemiluminescence analysis.

The role of nerve-induced release of nitric oxide (NO) as a modulator of neuroeffector transmission was studied in the longitudinal muscle of the guinea pig colon. The biological activity of a vascular relaxing factor released by nerve stimulation was examined in a bioassay cascade system. Furthermore, biochemical measurements of nerve-induced release of the NO metabolite nitrite (NO2-) were made with a chemiluminescence technique. Transmural nerve stimulation elicited contractile responses that were partly blocked by atropine and further inhibited after additional application of the tachykinin receptor antagonist CP-96, 345. The NO-synthase inhibitor N omega-nitro-L-arginine (NOARG) enhanced the nerve-induced contractions and concomitantly increased the basal degree of contraction ('tone'). The relaxations obtained by nerve stimulation after treatment with atropine and histamine were inhibited by NOARG. Electrical stimulation of the guinea pig colon released a non-adrenergic non-cholinergic (NANC) vascular relaxing factor into the tissue superfusate. The half-life of this factor down the cascade was the same as that observed with exogenous application of NO NOARG and tetrodotoxin (TTX) inhibited the release of the relaxing factor. During transmural nerve stimulation there was a significant increase in NO/NO2- release. This increase was inhibited by TTX and N omega-nitro-L-arginine methyl ester (L-NAME). In conclusion, pharmacological analysis as well as bioassay and biochemical measurements suggest that NO is released during nerve stimulation in the guinea pig colon, where it mediates smooth muscle relaxation.

Amino Acid Oxidoreductases↗
PubMed1994

Effect of inhaled nitric oxide on raised pulmonary vascular resistance in children with congenital heart disease.

OBJECTIVE: To study the short-term effects of inhaled nitric oxide in infants and young children with congenital heart disease. SETTING: A supraregional referral centre for children with congenital heart disease. PATIENTS AND METHODS: 22 infants and children aged 3-32 months (median age 5 months) with congenital heart disease undergoing preoperative cardiac catheterisation. All but one infant had intracardiac shunt lesions and 13 had increased pulmonary vascular resistance. During catheterisation the patients inhaled nitric oxide in a concentration of 40 parts per million in room air. Pulmonary and systemic haemodynamic variables were evaluated by means of measured oxygen consumption and the Fick principle before and after 10 minutes' exposure to nitric oxide. RESULTS: Inhaled nitric oxide did not affect the systemic circulation. There was a significant reduction in the pulmonary vascular resistance, but only in the 13 infants with pulmonary hypertension, in whom pulmonary vascular resistance was reduced by 34% from 8.6 (4.6) mm Hg.min.m2.l-1 (mean (SD)) to 5.7 (3.5) mm Hg.min.m2.l-1. The pulmonary circulation in infants with normal pulmonary vascular resistance was not affected. No statistically significant increase in methaemoglobin was seen, though there were large individual differences. No other side effects were seen. CONCLUSION: The present study shows that in infants with congenital heart disease inhaled nitric oxide reduced pathologically increased pulmonary vascular resistance without affecting systemic circulation and without important side effects with brief exposure.

Administration, Inhalation↗
PubMed1993

Endogenous nitric oxide counteracts antigen-induced bronchoconstriction.

In anesthetized, artificially ventilated guinea pigs immunized against ovalbumin, challenge with aerosolized ovalbumin (0.1 mg) elicited a substantial and sustained increase of insufflation pressure. The inhibitor of endogenous nitric oxide (NO) synthesis, L-NAME (N omega-nitro-L-arginine methylester, 30 mg kg-1 i.v.), markedly augmented the response, the potentiation of which could be prevented by NO (20 p.p.m.) in the inhaled air. The results indicate an inhibitory effect of endogenous NO on antigen-induced bronchoconstriction.

Aerosols↗
PubMed1993

Modulation of neuroeffector transmission by endogenous nitric oxide: a role for acetylcholine receptor-activated nitric oxide formation, as indicated by measurements of nitric oxide/nitrite release.

Nitric oxide (NO) synthase inhibitors enhanced nerve-mediated contractile responses in guinea pig ileum longitudinal muscle, likely via a prejunctional effect on substance P-like neuroeffector transmission. Supporting a modulatory role for NO, application of NO through administration of acid sodium nitrite evoked marked inhibitory effects on responses to transmural nerve stimulation. Substance P-like responses to nerve stimulation were abolished by substance P receptor antagonists and were enhanced by atropine, indicating a cholinergic influence on substance P-like neuroeffector transmission. Since acetylcholine can evoke release of NO from endothelium, the possible role of acetylcholine in NO release in ileum was examined. The release of NO/nitrite, determined by chemiluminescence, was inhibited by NG-monomethyl-L-arginine (L-NMMA), by calcium removal, by tetrodotoxin or by atropine, indicating a nerve-mediated control of NO production. A basis for the NO release is likely to be spontaneous neuronal activity, where release of acetylcholine, with subsequent muscarinic receptor activation, contributes to stimulation of NO formation.

Acetylcholine↗