5-Hydroxytryptamine- and U46619-mediated vasoconstriction in bovine pulmonary conventional and supernumerary arteries: effect of endogenous nitric oxide

1999 ◽  
Vol 98 (1) ◽  
pp. 81-89 ◽  
Author(s):  
D. BUNTON ◽  
A. MACDONALD ◽  
T. BROWN ◽  
A. TRACEY ◽  
J. C. MCGRATH ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Guanylate Cyclase ◽  
Vascular Tone ◽  
No Synthase ◽  
Vasoconstrictor Response ◽  
Cgmp Pathway ◽  
Endogenous Nitric Oxide ◽  
Synthase Inhibitor ◽  
Resting Tone

We compared 5-hydroxytryptamine (5-HT)- and U46619-mediated contractions in bovine pulmonary conventional arteries (CA) and supernumerary arteries (SA). The effects of the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) (100 μM) and the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 μM) on the responses of CA and SA to 5-HT and U46619 were also examined. In addition, the effects of the 5-HT2B receptor antagonist SB 200646 (1 nM–1 μM) on the responses to 5-HT in SA and CA were studied. Tissue cGMP levels were measured in the absence and presence of l-NAME, ODQ, 5-HT and U46619. 5-HT was approximately 30 times more potent in SA {-log [EC50 (M)] (pEC50) 6.32±0.13} than in CA (5.05±0.14). U46619 displayed a similar potency in both CA (pEC50 7.80±0.07) and SA (7.75±0.12). l-NAME did not significantly alter the resting tone of CA or SA. In contrast, ODQ produced a transient increase in the tone of both CA and SA. Neither l-NAME nor ODQ altered the responses to 5-HT or U46619 in CA. In addition, neither l-NAME nor ODQ altered the responses to U46619 in SA, but both l-NAME and ODQ increased the magnitude of the response to 5-HT in SA without changing the sensitivity. Inhibition of the 5-HT2B receptor with SB 200646 did not alter the response to 5-HT in SA or CA. Basal levels of cGMP (pmol/mg of protein) were similar in CA (1.16±0.33) and SA (0.8±0.51), and were not significantly changed in the presence of 5-HT or U46619. l-NAME and ODQ reduced the basal levels of cGMP in both SA and CA. The results suggest that endogenous NO selectively attenuates the vasoconstrictor response to 5-HT in SA, but not in CA. These results also suggest that the NO/cGMP pathway may have a role in maintaining low vascular tone, but that other mechanisms are able to compensate for the absence of this pathway.

Endogenous nitric oxide influences acetylcholine-induced bronchovascular dilation in sheep

1995 ◽  
Vol 78 (2) ◽  
pp. 539-545 ◽  
Author(s):  
F. Sasaki ◽  
P. Pare ◽  
D. Ernest ◽  
T. Bai ◽  
L. Verburgt ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Vascular Tone ◽  
No Synthase ◽  
Pulmonary Resistance ◽  
Similar Extent ◽  
Maximal Increase ◽  
Endogenous Nitric Oxide ◽  
Synthase Inhibitor ◽  
Endothelial Nitric Oxide

To test whether endogenous endothelial nitric oxide (NO) influences baseline bronchial vascular tone and mediates acetylcholine (ACh)-induced bronchial vascular dilation and/or modulates bronchoconstriction in ovine airways, we studied anesthetized ventilated open-chest sheep and measured bronchial blood flow (Qbr) and pulmonary resistance (RL). In six sheep we measured the response of Qbr and RL to the dose of ACh required to produce 50% of the maximal increase in Qbr at baseline during infusion of the NO synthase inhibitor NG-nitro-L-arginine (L-NNA; 10(-2) M). Infusion of L-NNA decreased both the baseline Qbr (28 +/- 13 to 8 +/- 2 ml/min, P < 0.01) and the change in Qbr (delta Qbr) from the baseline value (84 +/- 42 to 33 +/- 18 ml/min, P < 0.05). There was no difference in baseline RL or in the response of RL to ACh at any time. In another six sheep, phenylephrine (5 x 10(-6) to 5 x 10(-7) M) decreased baseline Qbr (22 +/- 6 to 10 +/- 3 ml/min, P < 0.05) but not delta Qbr (62 +/- 13 to 66 +/- 21 ml/min, not significant). Infusion of L-NNA in these sheep decreased the baseline Qbr to a similar extent (11 +/- 5 ml/min) and also decreased delta Qbr (42 +/- 16 ml/min, P < 0.05). We conclude that endogenous endothelial NO influences baseline vascular tone and ACh-induced vasodilation of the ovine bronchial vasculature but has no effect on baseline RL or ACh-induced bronchoconstriction.

Vasoactivity of the gasotransmitters hydrogen sulfide and carbon monoxide in the chicken ductus arteriosus

2011 ◽  
Vol 301 (4) ◽  
pp. R1186-R1198 ◽  
Author(s):  
Saskia van der Sterren ◽  
Pamela Kleikers ◽  
Luc J. I. Zimmermann ◽  
Eduardo Villamor
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Guanylate Cyclase ◽  
Vascular Tone ◽  
Soluble Guanylate Cyclase ◽  
Ductus Arteriosus ◽  
No Synthase ◽  
Mechanical Responses ◽  
Synthase Inhibitor

Besides nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H2S) is a third gaseous messenger that may play a role in controlling vascular tone and has been proposed to serve as an O2 sensor. However, whether H2S is vasoactive in the ductus arteriosus (DA) has not yet been studied. We investigated, using wire myography, the mechanical responses induced by Na2S (1 μM–1 mM), which forms H2S and HS− in solution, and by authentic CO (0.1 μM-0.1 mM) in DA rings from 19-day chicken embryos. Na2S elicited a 100% relaxation (pD2 4.02) of 21% O2-contracted and a 50.3% relaxation of 62.5 mM KCl-contracted DA rings. Na2S-induced relaxation was not affected by presence of the NO synthase inhibitor l-NAME, the soluble guanylate cyclase (sGC) inhibitor ODQ, or the K+ channel inhibitors tetraethylammonium (TEA; nonselective), 4-aminopyridine (4-AP, KV), glibenclamide (KATP), iberiotoxin (BKCa), TRAM-34 (IKCa), and apamin (SKCa). CO also relaxed O2-contracted (60.8% relaxation) and KCl-contracted (18.6% relaxation) DA rings. CO-induced relaxation was impaired by ODQ, TEA, and 4-AP (but not by l-NAME, glibenclamide, iberiotoxin, TRAM-34 or apamin), suggesting the involvement of sGC and KV channel stimulation. The presence of inhibitors of H2S or CO synthesis as well as the H2S precursor l-cysteine or the CO precursor hemin did not significantly affect the response of the DA to changes in O2 tension. Endothelium-dependent and -independent relaxations were also unaffected. In conclusion, our results indicate that the gasotransmitters H2S and CO are vasoactive in the chicken DA but they do not suggest an important role for endogenous H2S or CO in the control of chicken ductal reactivity.

Effect of l-NAME on oxygen uptake kinetics during heavy-intensity exercise in the horse

2001 ◽  
Vol 91 (2) ◽  
pp. 891-896 ◽  
Author(s):  
Casey A. Kindig ◽  
Paul McDonough ◽  
Howard H. Erickson ◽  
David C. Poole
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Electron Transport Chain ◽  
Slow Component ◽  
Oxygen Uptake Kinetics ◽  
No Synthase ◽  
Metabolic Rates ◽  
Transport Chain ◽  
Synthase Inhibitor ◽  
Reduced Time

There is evidence that oxidative enzyme inertia plays a major role in limiting/setting the O2 uptake (V˙o 2) response at the transition to higher metabolic rates and also that nitric oxide (NO) competitively inhibits V˙o 2 within the electron transport chain. To investigate whether NO is important in setting the dynamic response of V˙o 2 at the onset of high-intensity (heavy-domain) running in horses, five geldings were run on a treadmill across speed transitions from 3 m/s to speeds corresponding to 80% of peak V˙o 2with and without nitro-l-arginine methyl ester (l-NAME), an NO synthase inhibitor (20 mg/kg; order randomized). l-NAME did not alter (both P> 0.05) baseline (3 m/s, 15.4 ± 0.3 and 16.2 ± 0.5 l/min for control and l-NAME, respectively) or end-exerciseV˙o 2 (56.9 ± 5.1 and 55.2 ± 5.8 l/min for control and l-NAME, respectively). However, in the l-NAME trial, the primary on-kinetic response was significantly ( P < 0.05) faster (i.e., reduced time constant, 27.0 ± 2.7 and 18.7 ± 3.0 s for control andl-NAME, respectively), despite no change in the gain ofV˙o 2 ( P > 0.05). The faster on-kinetic response was confirmed independent of modeling by reduced time to 50, 63, and 75% of overallV˙o 2 response (all P < 0.05). In addition, onset of the V˙o 2 slow component occurred earlier (124.6 ± 11.2 and 65.0 ± 6.6 s for control and l-NAME, respectively), and the magnitude of the O2 deficit was attenuated (both P < 0.05) in the l-NAME compared with the control trial. Acceleration of the V˙o 2kinetics by l-NAME suggests that NO inhibition of mitochondrial V˙o 2 may contribute, in part, to the intrinsic metabolic inertia evidenced at the transition to higher metabolic rates in the horse.

scholarly journals Temperature conditioning of nasal air: effects of vasoactive agents and involvement of nitric oxide

1999 ◽  
Vol 87 (4) ◽  
pp. 1260-1265 ◽  
Author(s):  
William E. Holden ◽  
John P. Wilkins ◽  
Michelle Harris ◽  
Henry A. Milczuk ◽  
George D. Giraud
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Air Temperature ◽  
Vascular Tone ◽  
No Synthase ◽  
Saline Control ◽  
Vasoactive Agents ◽  
Exhaled No ◽  
No Release

Nitric oxide (NO) is released into nasal air, but its function is unknown. We hypothesized that nasal vascular tone and/or flow influences temperature conditioning of nasal air and that NO participates in this process. We measured nasal air temperature (via a thermocouple) and exhaled nasal NO release (by chemiluminescence) in five humans and examined the effects of an aerosolized vasoconstrictor (oxymetazoline), a vasodilator (papaverine), N G-nitro-l-arginine methyl ester, an inhibitor of NO synthase, or saline (control). Compared with saline (which caused no changes in nasal air temperature or exhaled NO release), oxymetazoline (0.05%) reduced nasal air temperature and NO release (130.8 ± 15.1 to 81.3 ± 12.8 nl ⋅ min−1 ⋅ m−2; P < 0.01). Papaverine (0.01 M) increased nasal air temperature and NO release (131.8 ± 13.1 to 157.2 ± 17.4 nl ⋅ min−1 ⋅ m−2; P < 0.03). N G-nitro-l-arginine methyl ester reduced nasal air temperature and NO release (123.7 ± 14.2 to 44.2 ± 23.7 nl ⋅ min−1 ⋅ m−2; P < 0.01). The results suggest that vascular tone and/or flow modulates temperature conditioning and that NO may participate in that function.

Nitric oxide and β-adrenergic agonist-induced bronchial arterial vasodilation

1997 ◽  
Vol 82 (2) ◽  
pp. 686-692 ◽  
Author(s):  
Nirmal B. Charan ◽  
Shane R. Johnson ◽  
S. Lakshminarayan ◽  
William H. Thompson ◽  
Paula Carvalho
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Methyl Ester ◽  
No Synthase ◽  
Ester Hydrochloride ◽  
Methyl Ester Hydrochloride ◽  
Adrenergic Agonist ◽  
Flow Probe ◽  
Cyclic Monophosphate ◽  
Synthase Inhibitor

Charan, Nirmal B., Shane R. Johnson, S. Lakshminarayan, William H. Thompson, and Paula Carvalho. Nitric oxide and β-adrenergic agonist-induced bronchial arterial vasodilation. J. Appl. Physiol. 82(2): 686–692, 1997.—In anesthetized sheep, we measured bronchial blood flow (Q˙br) by an ultrasonic flow probe to investigate the interaction between inhaled nitric oxide (NO; 100 parts/million) given for 5 min and 5 ml of aerosolized isoetharine (1.49 × 10−2 M concentration). NO and isoetharine increased Q˙br from 26.5 ± 6.5 to 39.1 (SE) ± 10.6 and 39.7 ± 10.7 ml/min, respectively ( n = 5). Administration of NO immediately after isoetharine further increasedQ˙br to 57.3 ± 15.1 ml/min. NO synthase inhibitor N ω-nitro-l-arginine methyl ester hydrochloride (l-NAME; 30 mg/kg, in 20 ml saline given iv) decreased Q˙br to 14.6 ± 2.6 ml/min. NO given three times alternately with isoetharine progressively increased Q˙br from 14.6 ± 2.6 to 74.3 ± 17.0 ml/min, suggesting that NO and isoetharine potentiate vasodilator effects of each other. In three other sheep, afterl-NAME, three sequential doses of isoetharine increased Q˙br from 10.2 ± 3.4 to 11.5 ± 5.7, 11.7 ± 4.7, and 13.3 ± 5.7 ml/min, respectively, indicating that effects of isoetharine are predominantly mediated through synthesis of NO. When this was followed by three sequential administrations of NO, Q˙br increased by 146, 172, and 185%, respectively. Thus in the bronchial circulation there seems to be a close interaction between adenosine 3′,5′-cyclic monophosphate- and guanosine 3′,5′-cyclic monophosphate-mediated vasodilatation.

scholarly journals Role of Nitric Oxide in Regulating Cerebrocortical Oxygen Consumption and Blood Flow during Hypercapnia

1994 ◽  
Vol 14 (3) ◽  
pp. 503-509 ◽  
Author(s):  
Ildiko Horvath ◽  
Norbert T. Sandor ◽  
Zoltan Ruttner ◽  
Alan C. McLaughlin
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Methyl Ester ◽  
Superior Sagittal Sinus ◽  
No Synthase ◽  
Sagittal Sinus ◽  
No Synthase Inhibitor ◽  
Synthase Inhibitor

The effect of the nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) on the response of cerebrocortical oxygen consumption (CMRO2) and blood flow (CBF) to two levels of hypercapnia (Paco2 ∼ 60 mm Hg and Paco2 ∼ 90 mm Hg) was investigated in ketamine-anesthetized rats. CBF was calculated using the Kety–Schmidt approach and CMRO2 was calculated from the product of CBF and the arteriovenous (superior sagittal sinus) difference for oxygen. l-NAME treatment did not have a significant effect on either CMRO2 or CBE under normocapnic conditions but inhibited the hypercapnic increase of CMRO2 and the hypercapnic increase in CBF. These results suggest that NO plays a role in the response of CMRO2 and CBF during hypercapnia and are consistent with the suggestion that at least part of the increase in CBF observed during hypercapnia is coupled to an increase in CMRO2.

Activation of Spinal N-methyl-D-aspartate Receptors Stimulates a Nitric Oxide/Cyclic Guanosine 3′,5′-monophosphate/Glutamate Release Cascade in Nociceptive Signaling 

1999 ◽  
Vol 91 (5) ◽  
pp. 1415-1415 ◽  
Author(s):  
Tomoyuki Kawamata ◽  
Keiichi Omote
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Nmda Receptors ◽  
Soluble Guanylate Cyclase ◽  
Glutamate Release ◽  
No Synthase ◽  
Nociceptive Transmission ◽  
Glutamate Concentration ◽  
Cgmp Pathway ◽  
Synthase Inhibitor

Background Increasing evidence has suggested the possibility that the activation of N-methyl-D-aspartate (NMDA) receptors modulates spinal nociceptive transmission via a nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) pathway. However, the existence and the role of an NO/cGMP pathway in the modulation of spinal nociceptive transmission has been unclear. The authors hypothesized that the activation of NMDA receptors stimulates an NO/cGMP pathway, and this pathway evokes glutamate release within the spinal cord, modulating spinal nociceptive transmission. Methods The authors have examined the effects of an NO synthase inhibitor and a soluble guanylate cyclase inhibitor on the concentrations of NO metabolites (NO2-/NO3-) and glutamate in the cerebrospinal fluid after intrathecal perfusion of NMDA, concomitantly observing pain-related behavior (scratching, biting, and vocalization) in unanesthetized, free-moving rats using an intrathecal microdialysis method. The contents of cGMP in the dorsal horn were also measured using enzyme immunoassay method. Results Intrathecal perfusion of NMDA produced pain-related behavior and increased glutamate and NO2-/NO3-concentrations in a dose-dependent manner. A competitive NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric acid, completely blocked the NMDA-induced responses. An NO synthase inhibitor, N(G)-monomethyl-L-arginine acetate, at a dose that completely blocked the increase in NO2-/NO3-, inhibited both the NMDA-induced pain-related behavior and the increase in glutamate concentration. In addition, a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazole[4,3-a]quinoxaline-1-one, also inhibited significantly NMDA-induced pain-related behavior and the increase in glutamate concentration. NMDA induced an increase in cGMP in the dorsal half of the spinal cord, which was blocked by N(G)-monomethyl-L-arginine acetate. Conclusions The results of this study support the hypothesis that the activation of NMDA receptors modulated pain-related behavior via an NO/cGMP/glutamate release cascade within the spinal cord.

Bicarbonate-dependent superoxide release and pulmonary artery tone

2003 ◽  
Vol 285 (6) ◽  
pp. H2327-H2335 ◽  
Author(s):  
Eva Nozik-Grayck ◽  
Yuh-Chin T. Huang ◽  
Martha Sue Carraway ◽  
Claude A. Piantadosi
Keyword(s):  
Methyl Ester ◽  
Pulmonary Artery ◽  
Vascular Tone ◽  
Plasma Membranes ◽  
Vascular Reactivity ◽  
No Synthase ◽  
Pulmonary Vasoconstriction ◽  
Anion Exchange Protein ◽  
Hypoxic Vasoconstriction ◽  
Synthase Inhibitor

Pulmonary vasoconstriction is influenced by inactivation of nitric oxide (NO) with extracellular superoxide ([Formula: see text]). Because the short-lived [Formula: see text] anion cannot diffuse across plasma membranes, its release from vascular cells requires specialized mechanisms that have not been well delineated in the pulmonary circulation. We have shown that the bicarbonate [Formula: see text] anion exchange protein (AE2) expressed in the lung also exchanges [Formula: see text] for [Formula: see text]. Thus we determined whether [Formula: see text] release involved in pulmonary vascular tone depends on extracellular [Formula: see text]. We assessed endothelium-dependent vascular reactivity and [Formula: see text] release in the presence or absence of [Formula: see text] in pulmonary artery (PA) rings isolated from normal rats and those exposed to hypoxia for 3 days. Lack of extracellular [Formula: see text] in normal PA rings significantly attenuated endothelial [Formula: see text] release, opposed hypoxic vasoconstriction, and enhanced acetylcholine-mediated vasodilation. Release of [Formula: see text] was also inhibited by an AE2 inhibitor (SITS) and abolished in normoxia by an NO synthase inhibitor ( NG-nitro-l-arginine methyl ester). In contrast, hypoxia increased PA AE2 protein expression and [Formula: see text] release; the latter was not affected by NG-nitro-l-arginine methyl ester or other inhibitors of enzymatic [Formula: see text] generation. Enhanced [Formula: see text] release by uncoupling NO synthase with geldanamycin was attenuated by hypoxia or by [Formula: see text] elimination. These results indicate that [Formula: see text] produced by endothelial NOS in normoxia and unidentified sources in hypoxia regulate pulmonary vascular tone via AE2.

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