Thrombin-induced vascular reactivity is modulated by ETB receptor-coupled nitric oxide release in rat aorta

1996 ◽  
Vol 271 (3) ◽  
pp. C923-C928 ◽  
Author(s):  
H. I. Magazine ◽  
K. D. Srivastava
Keyword(s):  
Nitric Oxide ◽  
Vascular Tone ◽  
Vascular Reactivity ◽  
Receptor Activation ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Receptor Antagonists ◽  
Receptor Modulation ◽  
No Release ◽  
Etb Receptor

The role of endothelin (ET) receptors in thrombin-induced modulation of vascular tone was evaluated by direct measurement of ET-1 and ET receptor-coupled nitric oxide (NO) release and developed isometric tension in thrombin-treated aortic rings. Here we report that rapid release of ET-1 and subsequent ETB receptor activation are required for production of the potent vasodilator NO by thrombin-stimulated aorta. Thrombin-induced NO release is ablated by pretreatment with ETB receptor antagonists or after ET receptor desensitization by repeated stimulation with ET-1. Thrombin-induced relaxation of precontracted vessels was abrogated in the presence of ETB receptor antagonists and, in contrast, marked contraction to thrombin was observed. These data indicate that the endothelium-dependent vasodilator activity previously attributed to thrombin is indirect and requires ETB receptor-coupled NO release and suggest that ET receptor modulation of thrombin-induced vascular tone may contribute to the increased vasomotor tone observed in diseased and mechanically injured vessels.

Endothelin and nitric oxide release modulate aortic contraction to selected thrombin receptor agonists

1996 ◽  
Vol 270 (6) ◽  
pp. C1815-C1818 ◽  
Author(s):  
H. I. Magazine ◽  
O. Butt ◽  
H. R. Yaghoutiel
Keyword(s):  
Nitric Oxide ◽  
Receptor Activation ◽  
Rat Aorta ◽  
Thrombin Receptor ◽  
Nitric Oxide Release ◽  
No Release ◽  
Limited Function ◽  
Specific Antagonist ◽  
Dose Dependent Increase ◽  
Dose Dependent

The contribution of endothelin-1 (ET-1) and nitric oxide (NO) release to vascular contraction induced by synthetic peptide agonists of the alpha-thrombin receptor, TRAP-14 and TRAP-6, was evaluated with the use of rings of rat aorta. TRAP-6 induced fourfold greater contraction than that induced by addition of TRAP-14. TRAP-14, but not TRAP-6, stimulation of aortic rings resulted in a rapid (in seconds) and dose-dependent increase in ET-1 levels detected in the vessel perfusate. Release of ET-1 in vessels denuded of endothelium was indistinguishable from that of intact vessels, suggesting that endothelial cells are not required for the observed ET-1 release. The contractile potency of TRAP-14 was reduced in the presence of BQ-123, a specific antagonist of the endothelin A subtype of ET receptors, whereas TRAP-14 potency was increased significantly by pretreatment with the NO synthetase inhibitor NG-nitro-L-arginine (L-NNA). The contractile potency of TRAP-6 was not altered in the presence of BQ-123 or L-NNA, suggesting that TRAP-14 but not TRAP-6 potency is modulated by ET-1 and NO release. These data indicate that TRAP-6 has limited function relative to TRAP-14 and that thrombin receptor activation is not sufficient to induce ET-1 and NO release from rat aorta.

Stimulation of the endogenous hydrogen sulfide synthesis suppresses oxidative–nitrosative stress and restores endothelial-dependent vasorelaxation in old rats

2020 ◽  
Vol 98 (5) ◽  
pp. 275-281 ◽  
Author(s):  
L.A. Mys ◽  
N.A. Strutynska ◽  
Y.V. Goshovska ◽  
V.F. Sagach
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Nitric Oxide Synthase ◽  
Vascular Reactivity ◽  
Nitrosative Stress ◽  
Rat Aorta ◽  
Aortic Tissue ◽  
Old Rats ◽  
Oxide Synthase ◽  
Stimulation Of

Hydrogen sulfide (H2S) is an endogenous gas transmitter with profound effects on the cardiovascular system. We hypothesized that stimulation of H2S synthesis might alleviate age-associated changes in vascular reactivity. Pyridoxal-5-phosphate (PLP), the coenzyme of H2S-synthesizing enzymes, was administrated to old male Wistar rats per os at a dose of 0.7 mg/kg body mass once a day for 2 weeks. H2S content in the aortic tissue, markers of oxidative stress, inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS), arginase activities, and endothelium-dependent vasorelaxation of the aortic rings were studied. Our results showed that PLP restored endogenous H2S and low molecular weight S-nitrosothiol levels in old rat aorta to the levels detected in adults. PLP significantly reduced diene conjugate content, hydrogen peroxide and peroxynitrite generation rates, and iNOS and arginase activity in the aortic tissue of old rats. PLP also greatly improved acetylcholine-induced relaxation of old rat aorta (47.7% ± 4.8% versus 18.4% ± 4.1% in old rats, P < 0.05) that was abolished by NO inhibition with N-nitro-l-arginine methyl ester hydrochloride (L-NAME) or H2S inhibition with O-carboxymethylhydroxylamine (O-CMH). Thus, PLP might be used for stimulation of endogenous H2S synthesis and correction of oxidative and nitrosative stress and vessel tone dysfunction in aging and age-associated diseases.

Androgen-receptor defect abolishes sex differences in nitric oxide and reactivity to vasopressin in rat aorta

2001 ◽  
Vol 91 (6) ◽  
pp. 2602-2610 ◽  
Author(s):  
John N. Stallone ◽  
Ronald L. Salisbury ◽  
Clifford T. Fulton
Keyword(s):  
Nitric Oxide ◽  
Androgen Receptor ◽  
Methyl Ester ◽  
Thoracic Aorta ◽  
Vascular Reactivity ◽  
Rat Aorta ◽  
Maximal Response ◽  
Maximal Contraction ◽  
Rat Thoracic Aorta ◽  
Recessive Defect

Contractions of rat thoracic aorta to vasopressin (VP) are threefold higher in females (F) than in males (M), primarily because nitric oxide (NO) attenuation of contraction is greater in M. To determine the role of the androgen receptor (AR) in this mechanism, vascular reactivity to VP was examined in thoracic aorta of the testicular-feminized male (Tfm) rat, which has an X-linked, recessive defect in AR function in affected M. Maximal contraction of normal aortas to VP was fourfold higher in F (4,128 ± 291 mg/mg ring wt) than in M (971 ± 133 mg); maximal response of Tfm (3,967 ± 253 mg) was similar to that of normal F. N G-nitro-l-arginine methyl ester increased maximal response to VP threefold in M but had no effect in F or Tfm. In contrast, maximal contraction of normal aortas to phenylephrine was 43% higher in M (4,011 ± 179 mg) than in F (2,809 ± 78 mg); maximal response of Tfm (2,716 ± 126 mg) was similar to that of normal F. N G-nitro-l-arginine methyl ester increased maximal response to phenylephrine by >50% in F and Tfm but had no effect in M. Maximal contractile response to 80 mM KCl did not differ among M, F, or Tfm. Thus androgens and normal vascular AR function are important in the greater NO-mediated attenuation of reactivity to VP in M than in F rat aorta, which may involve specific modulation of endothelial VP signal transduction pathways and NO release by androgens. These data also establish the importance of the Tfm rat as a model to study the effects of androgens on cardiovascular function.

Acute and chronic NOS inhibition enhances α2- adrenoreceptor-stimulated RhoA and Rho kinase in rat aorta

2002 ◽  
Vol 283 (4) ◽  
pp. H1361-H1369 ◽  
Author(s):  
Rebecca W. Carter ◽  
McKenzie Begaye ◽  
Nancy L. Kanagy
Keyword(s):  
Nitric Oxide ◽  
Drinking Water ◽  
Adrenergic Receptors ◽  
Membrane Fraction ◽  
Vascular Tone ◽  
Rho Kinase ◽  
Rat Aorta ◽  
No Synthase ◽  
Rhoa Activation

We demonstrated that arteries from rats made hypertensive with chronic nitric oxide (NO) synthase (NOS) inhibition ( N ω-nitro-l-arginine in drinking water, LHR) have enhanced contractile sensitivity to α2-adrenergic receptors (α2-AR) agonist UK-14304 compared with arteries from normotensive rats (NR). NO may regulate vascular tone in part through suppression of RhoA and Rho kinase (ROK). We hypothesized that enhanced RhoA and ROK activity augments α2-AR contraction in LHR aortic rings. Y-27632 eliminated UK-14304 contraction in LHR and NR aortic rings. The order of increasing sensitivity to Y-27632 was the following: endothelium-intact NR, LHR, and endothelium-denuded NR. UK-14304 stimulated RhoA translocation to the membrane fraction in LHR and denuded NR but not in intact NR aorta. Basally, more RhoA was present in the membrane fraction in denuded NR than in intact NR or LHR aorta. Relaxation to S-nitroso- N-acetyl-penicillamine and Y-27632 in denuded ionomycin-permeabilized rings was greater in NR than in LHR. Together these studies indicate α2-AR contraction depends on ROK activity more in NR than LHR aorta. Additionally, endogenous NO may regulate RhoA activation, whereas chronic NOS inhibition appears to cause RhoA desensitization.

Sexual dimorphism in vasopressin-induced contraction of rat aorta

1991 ◽  
Vol 260 (2) ◽  
pp. H453-H458 ◽  
Author(s):  
J. N. Stallone ◽  
J. T. Crofton ◽  
L. Share
Keyword(s):  
Estrous Cycle ◽  
Vascular Reactivity ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Female Rats ◽  
Male Rats ◽  
Maximal Response ◽  
Sprague Dawley ◽  
Tension Development ◽  
Sprague Dawley Rats

Previously, we reported that, in the rat, pressor responsiveness to vasopressin (VP) is higher in males than in females during most phases of the estrous cycle. To explore the role of the vasculature in this phenomenon, we examined vascular reactivity to VP in thoracic aortas of male rats and female rats during each phase of the estrous cycle. Aortic rings were prepared from age-matched male and female Sprague-Dawley rats and mounted for isometric tension recording. Maximal response of female aortas to VP (4,246 +/- 163 mg/mg ring dry wt) was more than twice (P less than 0.001) that of male aortas (1,877 +/- 215 mg/mg ring wt). Sensitivity of female aortas to VP was substantially higher (P less than 0.001) than that of male aortas (EC50: 10.9 +/- 0.7 vs. 19.0 +/- 1.6 nM, respectively). Maximal rate of tension development (dT/dtmax) during contraction with VP was nearly twofold higher (P less than 0.01) in female aortas (536 +/- 23 mg/min) than in male aortas (300 +/- 19 mg/min). Maximal response, sensitivity, and dT/dtmax of female aortas did not vary significantly during the estrous cycle. Maximal response of female aortas to phenylephrine (PE; 1,251 +/- 93 mg/mg ring wt) was half that (P less than 0.001) of male aortas (2,546 +/- 194 mg/mg ring wt); sensitivity to PE did not differ significantly (EC50: 0.33 +/- 0.02 vs. 0.38 +/- 0.06 microM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

L-arginine and Arginase Products Potentiate Dexmedetomidine-induced Contractions in the Rat Aorta

2018 ◽  
Vol 128 (3) ◽  
pp. 564-573 ◽  
Author(s):  
Emily S. W. Wong ◽  
Ricky Y. K. Man ◽  
Kwok F. J. Ng ◽  
Susan W. S. Leung ◽  
Paul M. Vanhoutte
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Immunofluorescent Staining ◽  
Sprague Dawley ◽  
Nitric Oxide Synthase Inhibitor ◽  
Cysteine Hydrochloride ◽  
Adrenergic Antagonist ◽  
Oxide Synthase

Abstract Background The α2-adrenergic sedative/anesthetic agent dexmedetomidine exerts biphasic effects on isolated arteries, causing endothelium-dependent relaxations at concentrations at or below 30 nM, followed by contractions at higher concentrations. l-arginine is a common substrate of endothelial nitric oxide synthase and arginases. This study was designed to investigate the role of l-arginine in modulating the overall vascular response to dexmedetomidine. Methods Isometric tension was measured in isolated aortic rings of Sprague Dawley rats. Cumulative concentrations of dexmedetomidine (10 nM to 10 μM) were added to quiescent rings (with and without endothelium) after previous incubation with vehicle, Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME; nitric oxide synthase inhibitor), prazosin (α1-adrenergic antagonist), rauwolscine (α2-adrenergic antagonist), l-arginine, (S)-(2-boronethyl)-l-cysteine hydrochloride (arginase inhibitor), NG-hydroxy-l-arginine (arginase inhibitor), urea and/or ornithine. In some preparations, immunofluorescent staining, immunoblotting, or measurement of urea content were performed. Results Dexmedetomidine did not contract control rings with endothelium but evoked concentration-dependent increases in tension in such rings treated with l-NAME (Emax 50 ± 4%) or after endothelium-removal (Emax 74 ± 5%; N = 7 to 12). Exogenous l-arginine augmented the dexmedetomidine-induced contractions in the presence of l-NAME (Emax 75 ± 3%). This potentiation was abolished by (S)-(2-boronethyl)-l-cysteine hydrochloride (Emax 16 ± 4%) and NG-hydroxy-l-arginine (Emax 18 ± 4%). Either urea or ornithine, the downstream arginase products, had a similar potentiating effect as l-arginine. Immunoassay measurements demonstrated an upregulation of arginase I by l-arginine treatment in the presence of l-NAME (N = 4). Conclusions These results suggest that when vascular nitric oxide homeostasis is impaired, the potentiation of the vasoconstrictor effect of dexmedetomidine by l-arginine depends on arginase activity and the production of urea and ornithine.

Different pharmacological characteristics of structurally similar benzylisoquinoline analogs, papaverine, higenamine, and GS 389, on isolated rat aorta and heart

1994 ◽  
Vol 72 (4) ◽  
pp. 327-334 ◽  
Author(s):  
Ki Churl Chang ◽  
Won Seog Chong ◽  
In Je Lee
Keyword(s):  
Heart Rate ◽  
Cyclic Amp ◽  
Rank Order ◽  
Receptor Activation ◽  
Rat Aorta ◽  
Isometric Tension ◽  
High K ◽  
Tissue Homogenates ◽  
Β Receptor ◽  
Isolated Rat

In the present study, we compared the pharmacological properties of structurally similar benzylisoquinoline compounds, papaverine, higenamine, and GS 389, using isolated rat aorta and atrial preparations. The three benzylisoquinoline compounds, concentration dependently, relaxed phenylephrine (3 μM) induced contraction of rat aortic rings, with the rank order of potency being higenamine > papaverine > GS 389. They also relaxed high K+ (60 mM) induced contraction, with the rank order of potency being papaverine > GS 389 [Formula: see text] higenamine. The relaxation was not modified by the presence of endothelium. To assess whether these compounds directly interfere with Ca2+ influx, the effects of these compounds on Ca2+-induced contraction in Ca2+-free media were examined. Among the three compounds, papaverine most strongly inhibited Ca2+-induced contraction of both K+ stimulated and phenylephrine-stimulated aorta. Higenamine was least potent in inhibition of Ca2+-induced contraction in high K+ depolarized aorta. In atrial tissues, lower concentrations of papaverine increased spontaneous beats and isometric tension, whereas above 30 μM its action was reversed. GS 389 decreased heart rate without affecting the contractility. On the other hand, higenamine concentration dependently increased both heart rate and isometric tension, as well as cyclic AMP levels in atrial tissues as a result of β-receptor activation. Cyclic AMP and cyclic GMP dependent phosphodiesterases from rat atrial and ventricular tissue homogenates were inhibited by papaverine and GS 389, but not by higenamine. These results suggest that calcium antagonistic action of these compounds is at least in part responsible for vasodilation action, but not for cardiac action. Dihydroxyl groups attached at C6 and C7 on the isoquinoline backbone appear to be responsible for altering the action of cardiac muscle.Key words: relaxation, Ca2+ antagonist, inotropic and chronotropic action, cyclic nucleotides.

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.

Halothane and Isoflurane Inhibit Vasodilation Due to Constitutive but Not Inducible Nitric Oxide Synthase

1996 ◽  
Vol 84 (5) ◽  
pp. 1156-1165 ◽  
Author(s):  
Zhiyi Zuo ◽  
Alexandra Tichotsky ◽  
Roger A. Johns
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Guanylyl Cyclase ◽  
Endothelial Nitric Oxide Synthase ◽  
Receptor Activation ◽  
Isometric Tension ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Inducible Nitric Oxide

Background Inhalational anesthetics inhibit the nitric oxide-guanylyl cyclase signaling pathway, but the site of this inhibition is not yet clear. This study was designed to test the hypothesis that receptor activation or downstream signaling events leading to nitric oxide synthase activation are important sites for this inhibition by comparing the effect of anesthetics on vasodilation caused by the calcium-dependent constitutive endothelial nitric oxide synthase versus the calcium-independent inducible nitric oxide synthase. Methods Endothelium-intact or -denuded rat thoracic aorta rings preincubated with or without lipopolysaccharide were mounted for isometric tension measurement, constricted with phenylephrine, then relaxed with methacholine in the presence or absence of halothane (1-3%) or isoflurane (1-3%). The cyclic guanosine 3,5-monophosphate content in the endothelium-denuded rings preincubated with or without lipopolysaccharide in the presence or absence of 3% halothane or 3% isoflurane was quantified by radioimmunoassay. The activity of partially purified inducible nitric oxide synthase from activated mouse macrophage was assayed in the presence or absence of halothane (1-4%) or isoflurane (1-5%) by the conversion of 3H-L-arginine to 3H-L-citrulline. Results Halothane and isoflurane inhibited methacholine-stimulated, nitric oxide-mediated vasorelaxation in endothelium-intact aortic rings. Neither halothane nor isoflurane affected the vasorelaxation caused by basal endothelial nitric oxide synthase or inducible nitric oxide synthase activity. Neither anesthetic altered the cyclic guanosine 3,5-monophosphate increase caused by inducible nitric oxide synthase in the lipopolysaccharide-treated rings. Conclusions The results demonstrated that halothane and isoflurane inhibit only receptor/calcium-activated nitric oxide synthase action and that direct inhibition of nitric oxide synthase, soluble guanylyl cyclase, or an interaction with nitric oxide are not responsible for anesthetic inhibition of endothelium-dependent vasorelaxation.

Importance of endothelium-derived nitric oxide in porcine coronary resistance arteries

1991 ◽  
Vol 260 (1) ◽  
pp. H13-H20 ◽  
Author(s):  
M. Tschudi ◽  
V. Richard ◽  
F. R. Buhler ◽  
T. F. Luscher
Keyword(s):  
Nitric Oxide ◽  
Vascular Tone ◽  
Isometric Tension ◽  
Coronary Resistance ◽  
Resistance Arteries ◽  
Adrenergic Agonist ◽  
Nitric Oxide Formation ◽  
Gi Protein ◽  
Endothelium Derived Relaxing Factor

Endothelial cells regulate vascular tone through the release of nitric oxide and other relaxing factors. The role of these substances was studied in isolated intramyocardial porcine coronary resistance arteries suspended in myographs for isometric tension recording. The inhibitor of nitric oxide formation NG-monomethyl-L-arginine (L-NMMA; 10(-7)-10(-4)M), but not D-NMMA, caused endothelium-dependent contractions that could be reversed by L-arginine but not by D-arginine. In preparations with endothelium, L-NMMA potentiated the contractions induced by acetylcholine and the relaxations to 3-morpholino-sydnonimine. Under both conditions, the effect of endothelial removal was slightly more pronounced than that of L-NMMA. Bradykinin, serotonin, and the alpha 2-adrenergic agonist clonidine evoked endothelium-dependent relaxations. L-NMMA as well as the inhibitor of guanylate cyclase methylene blue (10(-5) M) prevented the relaxations induced by clonidine, reduced those to serotonin, but hardly affected those to bradykinin. Thus, in porcine coronary resistance arteries, endothelium-derived nitric oxide is continuously produced from L-arginine. Endothelium-dependent relaxations to clonidine are fully mediated and those to serotonin partially mediated by nitric oxide; its release does not involve a Gi protein. An endothelium-derived relaxing factor different from nitric oxide must mediate the relaxations to bradykinin and contribute to those evoked by serotonin.

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