Functional difference between SP and NKA: relaxation of gastric muscle by SP is mediated by VIP and NO

1993 ◽  
Vol 264 (4) ◽  
pp. G678-G685
Author(s):  
J. G. Jin ◽  
S. Misra ◽  
J. R. Grider ◽  
G. M. Makhlouf
Keyword(s):  
Nitric Oxide ◽  
Circular Muscle ◽  
No Synthase ◽  
No Production ◽  
Neurokinin A ◽  
Functional Difference ◽  
Receptor Agonists ◽  
Gastric Muscle ◽  
Guinea Pig Stomach ◽  
Synthase Inhibitor

The mechanism of action of endogenous tachykinins [substance P (SP) and neurokinin A and B (NKA and NKB)] and of receptor-specific tachykinin analogues (SP methyl ester (SPME), [beta-Ala8]NKA-(4-10), and senktide) was examined in circular muscle of guinea pig stomach. Cross-desensitization studies confirmed that SPME and SP interacted with NK-1 receptors, [beta-Ala8]NKA-(4-10) and NKA with NK-2 receptors, and senktide and NKB with NK-3 receptors. NK-1 and NK-3-receptor agonists induced relaxation and stimulated vasoactive intestinal peptide (VIP) release and nitric oxide (NO) production: tetrodotoxin abolished VIP release, NO production, and relaxation, converting the response to NK-1-receptor agonists to contraction; the NO synthase inhibitor NG-nitro-L-arginine (L-NNA) abolished NO production, partly inhibited VIP release (56-64%, P < 0.01), and abolished relaxation; the VIP antagonist VIP-(10-28) partly inhibited NO production (73-74%, P < 0.001) and relaxation (56-58%, P < 0.01); and atropine augmented relaxation by 28-35% (P < 0.01). The pattern of inhibition implied that: 1) relaxation was mediated by VIP and NO; 2) VIP release was partly dependent on NO production, since it was strongly inhibited by L-NNA; and 3) NO was largely produced by the action of VIP on muscle cells, since it was strongly inhibited by VIP-(10-28). NK-2-receptor agonists elicited only contraction that was not affected by tetrodotoxin; these agonists also inhibited VIP release, NO production, and relaxation induced by NK-1- and NK-3-receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release

1992 ◽  
Vol 262 (4) ◽  
pp. G774-G778 ◽  
Author(s):  
J. R. Grider ◽  
K. S. Murthy ◽  
J. G. Jin ◽  
G. M. Makhlouf
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Muscle Cells ◽  
No Synthase ◽  
No Production ◽  
Field Stimulation ◽  
Relaxant Effect ◽  
Gastric Muscle ◽  
Synthase Inhibitor ◽  
Stimulation Of

The source of nitric oxide (NO) and its role in neurally induced relaxation was examined in smooth muscle of the stomach and tenia coli. Field stimulation of gastric muscle strips was accompanied by frequency-dependent relaxation, vasoactive intestinal peptide (VIP) release, and NO production: the NO synthase inhibitor, NG-nitro-L-arginine (L-NNA) completely inhibited NO production and partly inhibited VIP release (52-54%) and relaxation (58-88%); inhibition of all three functions was reversed by L-arginine but not by D-arginine. In isolated gastric muscle cells, VIP caused relaxation and stimulated NO production: L-NNA completely inhibited NO production and partly inhibited relaxation; the inhibition was reversed by L-arginine but not by D-arginine. Abolition of NO production with only partial inhibition of relaxation implied that NO production from muscle cells induced by the action of VIP was partly responsible for relaxation. By contrast, field stimulation of tenia coli was accompanied by relaxation and VIP release but not by NO production. Neither VIP release nor relaxation was affected by L-NNA. In isolated muscle cells of tenia coli, VIP caused relaxation but did not stimulate NO production; relaxation in these cells was not affected by L-NNA. We conclude that 1) VIP is the primary relaxant transmitter in both gastric muscle and tenia coli, 2) the release of VIP in gastric muscle but not in tenia coli stimulates NO production from target muscle cells, and 3) NO amplifies the relaxant effect of VIP in muscle cells and acts presynaptically to enhance the release of VIP.

Regulation of Ca(2+)-dependent nitric oxide synthase in bovine aortic endothelial cells

1995 ◽  
Vol 269 (3) ◽  
pp. C757-C765 ◽  
Author(s):  
B. J. Buckley ◽  
Z. Mirza ◽  
A. R. Whorton
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
No Synthase ◽  
No Production ◽  
Intact Cells ◽  
Aortic Endothelial Cells ◽  
A 23187 ◽  
Transient Rise ◽  
Synthase Inhibitor ◽  
Sustained Increase

Vascular endothelium responds to Ca(2+)-mobilizing agonists by producing nitric oxide (NO), a potent vasodilator and inhibitor of platelet aggregation. Regulation of constitutively expressed endothelial NO synthase (eNOS) in intact cells is not well understood. We investigated the kinetics of NO formation in response to Ca(2+)-mobilizing agonists, the requirement for extracellular L-arginine, and the role of NO in regulating eNOS activity. When endothelial cells were stimulated with bradykinin and ATP in the presence of 100 microM L-arginine, we observed a rapid and transient rise in intracellular Ca2+ concentration ([Ca2+]i) from 50 +/- 8 nM to 698 +/- 74 and 637 +/- 53 nM, respectively, and a rapid and transient rise in NO production from a basal level of 37 pmol.min-1.mg protein-1 to 256 and 275 pmol.min-1.mg protein-1, respectively. When cells were stimulated with A-23187 or thapsigargin in the presence of 100 microM L-arginine, we observed a sustained increase in [Ca2+]i and a sustained increase in NO production. The rate of NO synthesis was linear over 30 min, rising above control levels of 7 pmol/min to 53 pmol/min for A-23187 and 62 pmol/min for thapsigargin. Thapsigargin stimulated NO production and [Ca2+]i with 50% effective concentration values of 0.01 and 0.05 microM, respectively. Ca(2+)-stimulated NO production was attenuated by the NO synthase inhibitor NG-monomethyl-L-arginine, the removal of extracellular L-arginine, and the Ca(2+)-chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. When we exposed cells to NO gas (3.1 mM for 15 min) and S-nitrosoglutathione (10 mM for 1 h) thapsigargin-stimulated NO production was decreased by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of prostanoid vasomotor effects and receptors in choroidal vessels of newborn pigs

1997 ◽  
Vol 272 (3) ◽  
pp. R995-R1001 ◽  
Author(s):  
D. Abran ◽  
D. R. Varma ◽  
S. Chemtob
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
No Production ◽  
Camp Production ◽  
Nitrite Oxidation ◽  
Vascular Effects ◽  
Inositol 1,4,5 Trisphosphate ◽  
Newborn Pigs ◽  
Synthase Inhibitor ◽  
Choroidal Vessels

This study was conducted to determine if high perinatal prostaglandin (PG) and thromboxane (TxA2) levels modified their choroidal vasomotor effects and receptor levels. Both nonperfused (eyecup preparations) and perfused choroidal vessels from saline- or ibuprofen-treated 1-day-old pigs and tissues from adult pigs were used; all prostanoids produced similar vasomotor effects on both preparations. Choroidal PGF2alpha, TxA2, PGI2, and PGD2 levels were higher in the newborn than in adult pigs; injections of ibuprofen (40 mg/kg every 4 h for 48 h) into newborn pigs significantly decreased choroidal levels of all these prostanoids. PGF2alpha and the TxA2 mimetic U-46619 caused less choroidal vasoconstriction and production of inositol 1,4,5-trisphosphate (IP3) in the newborn than in adult pigs. Ibuprofen treatment increased choroidal PGF2alpha vasoconstrictor effects, IP3 production, and receptors, but did not modify response to U-46619. Carbaprostacyclin (PGI2 analog) caused a greater choroidal vasodilatation and adenosine adenosine 3',5'-cyclic monophosphate (cAMP) production in the newborn than in adult pigs; these effects were not modified by ibuprofen. PGD2 did not increase cAMP but caused greater dilatation and nitrite [oxidation product of nitric oxide (NO)] production in the choroid of newborn than of adult pigs, which were decreased to adult levels by ibuprofen and the NO synthase inhibitor N(omega)-nitro-L-arginine. These data suggest that high perinatal PG levels downregulate PGF2alpha receptors and vascular effects but do not modify choroidal responses to TxA2 and PGI2; NO seems to contribute to the vasodilator effects of PGD2.

Dynamic changes in nitric oxide and mitochondrial oxidative stress with site-dependent differential tissue response during anoxic preconditioning in rat heart

2007 ◽  
Vol 293 (3) ◽  
pp. H1457-H1465 ◽  
Author(s):  
Dang Van Cuong ◽  
Mohamad Warda ◽  
Nari Kim ◽  
Won Sun Park ◽  
Jae Hong Ko ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Rat Heart ◽  
No Synthase ◽  
Tissue Response ◽  
No Production ◽  
Dynamic Changes ◽  
Mitochondrial Oxidative Stress ◽  
Mitochondrial Superoxide ◽  
Inducible No Synthase ◽  
Synthase Inhibitor

In this study, dynamic changes in nitric oxide (NO) and mitochondrial superoxide (O2•−) were examined during anoxic preconditioning (AP) in rat heart model. AP and anoxia-reoxygenation (A/R) were performed on isolated hearts and single cardiomyocytes. The cellular insult in the form of infarct size and DNA damage were localized and correlated with NO synthases (endothelial and inducible) expression levels. The results showed that endocardium was the most affected region in AP groups, whereas the larger area of infarct was confined to mid- and epicardium in the A/R group. Interestingly, a high-level expression of immunofluorescent NO synthases was restricted to viable areas in the AP. In contrast to the gradual increase in O2•− level that occurred in the AP group, a sudden massive increase in its level was demonstrated at the onset of reoxygenation in the A/R group. The observed increase in NO production during reoxygenation in the AP group was attenuated by inducible NO synthase inhibitor. The study revealed, on a real-time basis, the role played by preconditioning for modulating NO and O2•− levels on behalf of cell survival. The results afford a better understanding of cardiac-adapting mechanism during AP and the role of inducible NO synthase in this important phenomenon.

scholarly journals l-Arginine attenuates lipopolysaccharide-induced lung chemokine production

2001 ◽  
Vol 280 (3) ◽  
pp. L400-L408 ◽  
Author(s):  
Casey M. Calkins ◽  
Denis D. Bensard ◽  
Julie K. Heimbach ◽  
Xianzhong Meng ◽  
Brian D. Shames ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dna Binding ◽  
Nuclear Factor Κb ◽  
No Synthase ◽  
No Production ◽  
Nuclear Factor ◽  
Rat Lung ◽  
Neutrophil Accumulation ◽  
Chemokine Production ◽  
Synthase Inhibitor

Chemokines stimulate the influx of leukocytes into tissues. Their production is regulated by nuclear factor-κB (NF-κB), an inducible transcription factor under the control of inhibitory factor κB-α (IκB-α). We have previously demonstrated that l-arginine (l-Arg) attenuates neutrophil accumulation and pulmonary vascular injury after administration of lipopolysaccharide (LPS). We hypothesized thatl-Arg would attenuate the production of lung chemokines by stabilizing IκB-α and preventing NF-κB DNA binding. We examined the effect of l-Arg on chemokine production, IκB-α degradation, and NF-κB DNA binding in the lung after systemic LPS. To block nitric oxide (NO) production, a NO synthase inhibitor was given before l-Arg. LPS induced the production of chemokine protein and mRNA. l-Arg attenuated the production of chemokine protein and mRNA, prevented the decrease in IκB-α levels, and inhibited NF-κB DNA binding. NO synthase inhibition abolished the effects of l-Arg on all measured parameters. Our results suggest that l-Arg abrogates chemokine protein and mRNA production in rat lung after LPS. This effect is dependent on NO and is mediated by stabilization of IκB-α levels and inhibition of NF-κB DNA binding.

Nitric oxide contributes to 20-HETE-induced relaxation of pulmonary arteries

2002 ◽  
Vol 93 (4) ◽  
pp. 1391-1399 ◽  
Author(s):  
Ming Yu ◽  
Ryan P. McAndrew ◽  
Rula Al-Saghir ◽  
Kristopher G. Maier ◽  
Meetha Medhora ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Calcium Concentration ◽  
Pulmonary Arteries ◽  
No Synthase ◽  
No Production ◽  
Peripheral Arteries ◽  
Cyclooxygenase Inhibitor ◽  
No Release ◽  
Synthase Inhibitor ◽  
Cytochrome P 450

In contrast to its constrictor effects on peripheral arteries, 20-hydroxyeicosatetraenoic acid (20-HETE) is an endothelial-dependent dilator of pulmonary arteries (PAs). The present study examined the hypothesis that the vasodilator effects of 20-HETE in PAs are due to an elevation of intracellular calcium concentration ([Ca2+]i) and the release of nitric oxide (NO) from bovine PA endothelial cells (BPAECs). BPAECs express cytochrome P-450 4A (CYP4A) protein and produce 20-HETE. 20-HETE dilated PAs preconstricted with U-46619 or norepinephrine and treated with the cytochrome P-450 inhibitor 17-octadecynoic acid and the cyclooxygenase inhibitor indomethacin. The dilator effect of 20-HETE was blocked by the NO synthase inhibitor N ω-nitro-l-arginine methyl ester (l-NAME) or by removal of endothelium. 20-HETE significantly increased [Ca2+]i and NO production in BPAECs. 20-HETE-induced NO release was blunted by removal of extracellular calcium, as well as NO synthase inhibitors (l-NAME). These results suggest that 20-HETE dilates PAs at least in part by increasing [Ca2+]i and NO release in BPAECs.

Shear-dependent release of venular nitric oxide: effect on arteriolar tone in rat striated muscle

1996 ◽  
Vol 271 (2) ◽  
pp. H387-H395 ◽  
Author(s):  
M. A. Boegehold
Keyword(s):  
Nitric Oxide ◽  
Shear Rate ◽  
Striated Muscle ◽  
No Synthase ◽  
No Production ◽  
Contracting Muscle ◽  
Divergent Flow ◽  
Synthase Inhibitor ◽  
Arteriolar Tone ◽  
Resting Muscle

This study was designed to determine whether shear-dependent changes in venular nitric oxide (NO) production can influence nearby arteriolar tone and whether this mechanism contributes to functional arteriolar dilation in contracting muscle. In resting spinotrapezius muscle of anesthetized rats, occlusion of one branch of an arcade venular bifurcation with divergent flow caused flow and wall shear rate in the parallel branch to increase by an average of 99 and 72%, respectively. After 10–30 s, the paired arcade arteriole dilated by an average of 30%, with a correlation between the increase in venular shear rate and the magnitude of arteriolar dilation. During muscle contraction, arcade arterioles dilated by 73–97% and arcade venular shear rate increased by 48–83%. The NO synthase inhibitor NG-monomethyl-L-arginine greatly attenuated arteriolar dilation to increased venular shear rate in resting muscle but did not affect arteriolar dilation in contracting muscle. These findings suggest that a shear-dependent increase in venular NO release can dilate nearby arterioles, but this mechanism is not important for the sustained dilation of these arterioles during functional hyperemia.

Chronic hypertension impairs flow-induced vasodilation and augments the myogenic response in fetal lung

2002 ◽  
Vol 282 (1) ◽  
pp. L56-L66 ◽  
Author(s):  
Laurent Storme ◽  
Thomas A. Parker ◽  
John P. Kinsella ◽  
Robyn L. Rairigh ◽  
Steven H. Abman
Keyword(s):  
Nitric Oxide ◽  
Ductus Arteriosus ◽  
Fetal Lung ◽  
No Synthase ◽  
Chronic Hypertension ◽  
No Production ◽  
Myogenic Response ◽  
Hemodynamic Effects ◽  
No Signaling ◽  
Synthase Inhibitor

We hypothesized that altered vasoreactivity in perinatal pulmonary hypertension (PH) is characterized by abnormal responses to hemodynamic stress, including the loss of flow-induced vasodilation and an augmented myogenic response. Therefore, we studied the acute hemodynamic effects of brief compression of the ductus arteriosus (DA) in control fetal lambs and in lambs during exposure to chronic PH. In both groups, acute DA compression decreased pulmonary vascular resistance (PVR) by 20% at baseline ( day 0). After 2 days of hypertension, acute DA compression paradoxically increased PVR by 50% in PH lambs, whereas PVR decreased by 25% in controls. During the 8-day study period, PVR increased during acute DA compression in PH lambs, whereas acute DA compression continued to cause vasodilation in controls. Brief treatment with the nitric oxide (NO) synthase inhibitor nitro-l-arginine (l-NA) increased basal PVR in control but not PH lambs, suggesting decreased NO production in PH lambs. Chronic hypertension increased the myogenic response afterl-NA in PH lambs, whereas the myogenic response remained unchanged in controls. The myogenic response was inhibited by nifedipine in PH lambs, suggesting that the myogenic response is dependent upon the influx of extracellular calcium. We conclude that chronic PH impairs flow-induced vasodilation and increases the myogenic response in fetal lung. We speculate that decreased NO signaling and an augmented myogenic response contributes to abnormal vasoreactivity in PH.

scholarly journals The Effect of the Nitric Oxide Synthase Inhibitor L-NMMA on Basal CBF and Vasoneuronal Coupling in Man: A PET Study

1999 ◽  
Vol 19 (6) ◽  
pp. 673-678 ◽  
Author(s):  
Richard P. White ◽  
Claire Hindley ◽  
Peter M. Bloomfield ◽  
Vincent J. Cunningham ◽  
Patrick Vallance ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Animal Models ◽  
No Synthase ◽  
No Production ◽  
Finger Movements ◽  
Nitric Oxide Synthase Inhibitor ◽  
Positron Emission ◽  
Animal Data ◽  
Before And After ◽  
Synthase Inhibitor

Nitric oxide (NO) regulates basal CBF. In a number of animal models NO has been implicated in the mediation of the regional changes in CBF (rCBF) that accompany neuronal activation (vasoneuronal coupling). However, some results in animal models have failed to confirm this finding, and the validity of extrapolation to man from animal data is uncertain. To determine the contribution of NO to basal global CBF and activation-induced changes in rCBF, the authors have performed quantitative H215O positron emission tomography (PET) studies before and after administration of the non-isoform-specific NO synthase inhibitor, NG-monomethyl-l-arginine (L-NMMA), in 10 healthy male volunteers. Learning a novel sequence of finger movements was used as a paradigm to induce regional frontal cortex activation. The effect of NO synthase inhibition on the magnitude and pattern of activation was determined. Resting global CBF fell from 33.3 ± 5.3 mL·100 g−1·min−1 at rest before L-NMMA, to 26.5 ± 7.7 mL·100 g−1·min−1 after L-NMMA ( P = 0.001). This fall was reversed by l-arginine administration. Learning sequential finger movements induced increases in rCBF in the left motor, right prefrontal, and bilateral premotor cortices. After NO synthase inhibition with L-NMMA, there was no change in this pattern of activation and no reduction in the magnitude of rCBF responses at the foci of maximal stimulation before and after L-NMMA. These findings confirm that NO production contributes to basal CBF regulation in man, but show that systemic NO synthase inhibition with L-NMMA does not impair regional vasoneuronal coupling.

Increased nitric oxide activity in early renovascular hypertension

1996 ◽  
Vol 270 (1) ◽  
pp. R118-R124 ◽  
Author(s):  
R. K. Dubey ◽  
M. A. Boegehold ◽  
D. G. Gillespie ◽  
M. Rosselli
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
No Synthase ◽  
No Production ◽  
Compensatory Mechanism ◽  
Hypertensive Rats ◽  
Peripheral Vasculature ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor ◽  
Circulating Levels

A decreased influence of nitric oxide (NO) in the peripheral vasculature is associated with the pathophysiology of established hypertension, and some studies suggest that increased blood pressure positively correlates with decreased NO production. If so, then the increased arterial pressure in one-kidney, one-clip (1K1C) hypertensive rats should be associated with decreased circulating levels of nitrite/nitrate (NO2/NO3; stable metabolites of NO) and guanosine 3',5'-cyclic monophosphate (cGMP; mediator of NO action). We measured serum NO2/NO3 and cGMP levels in early hypertensive 1K1C (2 wk after clipping) and shamoperated one-kidney (1K) normotensive rats, treated orally with or without the NO-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 2 wk). Compared with those in 1K rats, NO2/NO3 and cGMP levels were increased in 1K1C hypertensive rats but not in 1K1C rats treated with L-NAME. NO2/NO3 and cGMP levels in L-NAME-treated 1K and 1K1C rats were similar. Compared with that in 1K rats, systolic blood pressure (SBP) was increased in 1K1C rats and in L-NAME-treated 1K and 1K1C rats. The SBP increase in L-NAME-treated 1K1C rats was more rapid than in untreated 1K1C rats. In early hypertension, increases in SBP positively correlated with increases in serum NO2/NO3 and cGMP. After 2 wk of hypertension, circulating NO2/NO3 levels gradually declined and reached prehypertension levels by the fifth week of hypertension. These results provide evidence for increased NO synthesis in early hypertensive 1K1C rats, and this increased NO could be a compensatory mechanism to slow the development of hypertension in these animals.

Sign in / Sign up

Export Citation Format

Share Document