scholarly journals 18b-glycyrrhetinic acid increases blood pressure in rats through the action on myoendothelial gap junctions

2021 ◽  
Vol 67 (4) ◽  
pp. 29-36
Author(s):  
A.S. Khromov ◽  
◽  
N.V. Dobrelia ◽  
I.V. Ivanova ◽  
A.I. Soloviev ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Gap Junctions ◽  
Antimicrobial Properties ◽  
Glycyrrhetinic Acid ◽  
High Biological Activity ◽  
Nitric Oxide Synthase Inhibitor ◽  
Pentacyclic Triterpenoid ◽  
Arterial Blood ◽  
Dilatory Response ◽  
Synthase Inhibitor

18b-glycyrrhetinic acid (GA), a pentacyclic triterpenoid found in the roots of licorice plants (Glycyrrhiza glabra), posseses high biological activity, including anti-inflammatory and antimicrobial properties. Additionally, it effectively blocks myoendothelial gap junctions. Our experiments on adult Wistar rats have shown that GA administration via gavage in the dose 0.015 g per 100 g of body weight caused a significant increase in arterial blood pressure measured both invasively and non-invasively as early as on the 7th day after beginning of the treatment. Further administration of GA up to 21 days did not change blood pressure significantly. Thoracic aortic rings obtained from GA-treated animals demonstrated a decreased ability to relax in response to acetylcholine (ACh): the maximal dilatory response and the sensitivity of the vascular preparations to ACh measured as pD2 (-log ЕС50) were significantly suppressed compared to the relaxant responses of rings from untreated rats. GA externally applied to intact tissues at a concentration of 2×10-5 M inhibited the ACh-induced relaxation. The inhibition was more pronounced than that observed in vascular rings obtained from the GA-treated animals. Nevertheless, it was smaller than that observed under combined action of the nitric oxide synthase inhibitor, L-NAME, and indomethacin, indicating that GA affects preferentially EDHF-dependent component of the ACh-induced relaxation. These results may suggest that damage of myoendothelial gap junctions that provide electrical communication between the endothelium and the smooth muscle layers may, at least partially, cause the development of arterial hypertension under GA treatment.

Nitric oxide-independent effects of tempol on sympathetic nerve activity and blood pressure in normotensive rats

2001 ◽  
Vol 281 (2) ◽  
pp. H975-H980 ◽  
Author(s):  
Hui Xu ◽  
Gregory D. Fink ◽  
Alex Chen ◽  
Stephanie Watts ◽  
James J. Galligan
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Cardiovascular Responses ◽  
Nerve Activity ◽  
Nitric Oxide Synthase Inhibitor ◽  
Arterial Blood ◽  
Independent Effects ◽  
Synthase Inhibitor

The role of the sympathetic nervous system in 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol)-induced cardiovascular responses in urethane-anesthetized, normotensive rats was evaluated. Tempol caused dose-dependent (30–300 μmol/kg iv) decreases in renal sympathetic nerve activity (RSNA), mean arterial blood pressure (MAP), and heart rate (HR). Similar responses were obtained after sinoaortic denervation and cervical vagotomy. These responses were not blocked following treatment with the nitric oxide synthase inhibitor N G-nitro-l-arginine (2.6 mg · kg−1 · min−1 iv for 5 min) or the α2-adrenergic receptor antagonist idazoxan (0.3 mg/kg iv bolus). Idazoxan blocked the effects of clonidine (10 μg/kg iv) on HR, MAP, and RSNA. Hexamethonium (30 mg/kg iv) inhibited RSNA, and tempol did not decrease RSNA after hexamethonium. The effects of tempol on HR and MAP were reduced by hexamethonium. In conclusion, depressor responses caused by tempol are mediated, partly, by sympathoinhibition in urethane-anesthetized, normotensive rats. Nitric oxide does not contribute to this response, and the sympathoinhibitory effect of tempol is not mediated via α2-adrenergic receptors. Finally, tempol directly decreases HR, which may contribute to the MAP decrease.

Nitric Oxide in Streptozotocin-Induced Diabetes Mellitus in Rats

1996 ◽  
Vol 90 (5) ◽  
pp. 379-384 ◽  
Author(s):  
Abed Maree ◽  
Gari Peer ◽  
Adrian Iaina ◽  
Miriam Blum ◽  
Yoram Wollman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Body Weight ◽  
Nitric Oxide Synthase ◽  
Creatinine Clearance ◽  
Diabetic Rats ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor ◽  
Oxide Synthase

1. The present study was performed to determine the relationship between diabetic glomerular hyperfiltration and nitic oxide as modulated by the chronic administration of l-arginine and/or N-ω-nitro-l-arginine, a known nitric oxide synthase inhibitor in streptozotocin-induced diabetic rats. 2. Normal rats and rats drinking hypertonic glucose (10%) were used as time-controlled groups. Six weeks after administration of streptozotocin the diabetic rats had significantly higher creatinine clearance (667 ± 53 μl min−1 100 g−1 body weight) than before and streptozotocin (456 ± 38 μl min−1 100 g−1 body weight, P<0.005) and very high plasma (37.8 ± 10.9 μmol/l) and urinary (3.492 ± 0.179 nmol min−1 100 g−1 body weight) nitrite + nitrate (stable metabolites of nitric oxide) values compared with before streptozotocin administration [19.3 ± 2.8 μmol/l (P<0.001) and 0.420 ± 0.051 nmol min−1 100 g−1 body weight (P<0.001) respectively]. The 6-week diabetic rats had higher systolic blood pressure (124.2 ± 2.9 mm Hg, P<0.05) than before streptozotocin (108 ± 8 mmHg), but had a value similar to that of the hypertonic-glucose-drinking rats. 3. The diabetic rats supplemented with l-arginine did not show an increase in creatinine clearance and had a lower urinary excretion of nitrite + nitrate (0.999 ± 0.27 nmol min−1 100 g−1 body weight, P<0.005) than the respective untreated streptozotocin-induced diabetic rats. Creatinine clearance increased in the normal and glucose-drinking rats that received l-arginine. The administration of l-arginine resulted in significant reduction in blood pressure in all groups studied. The chronic nitric oxide synthase inhibitor resulted in high blood pressure, and in a significant decrease in creatinine clearance and urinary nitrite + nitrate excretion in all groups studied. In both diabetic and glucose-drinking rats, the l-arginine therapy resulted in significantly lower plasma and urinary glucose levels than in their respective untreated control groups. 4. The nitric oxide synthase inhibitor increased the plasma and urinary glucose concentration in both diabetic and glucose-drinking rats. 5. Our results indicate that diabetic rats are characterized by high plasma concentrations and elevated urinary excretion of nitrite + nitrate, suggesting a state of high nitric oxide production. The vascular response to nitric oxide in diabetic rats may be different at the glomerular and peripheral vascular bed.

scholarly journals A role for the thromboxane receptor in l-NAME hypertension

2008 ◽  
Vol 295 (4) ◽  
pp. F1096-F1102 ◽  
Author(s):  
Helene Francois ◽  
Natalia Makhanova ◽  
Philip Ruiz ◽  
Jonathan Ellison ◽  
Lan Mao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Kidney Injury ◽  
Lipid Mediator ◽  
Wild Type ◽  
Nitric Oxide Synthase Inhibitor ◽  
Tp Receptor ◽  
Tp Receptors ◽  
Synthase Inhibitor

Actions of the lipid mediator thromboxane (Tx) A2 acting through the TP receptor contribute to the pathogenesis of cardiovascular disease. To further explore the role of TxA2 in hypertension, we examined the consequences of deficiency of the TP receptor on the course of hypertension associated with endothelial dysfunction and salt sensitivity. To this end, the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) was administered to TP-deficient ( Tp−/−) and wild-type ( Tp+/+) control mice in drinking water for 21 wk along with a high-salt (HS; 6% NaCl) diet. Administration of l-NAME increased urinary excretion of TxB2 to a similar extent in both Tp+/+ and Tp−/− animals. l-NAME also caused significant and sustained elevations in blood pressure that reached a maximum between weeks 3 and 6. However, the severity of hypertension was attenuated in the Tp−/− mice throughout the study period ( P < 0.001). At the end of the study, the wild-type mice developed significant cardiac hypertrophy (23.6 ± 2% increase in heart-to-body weight ratio). The severity of cardiac hypertrophy was attenuated in the TP-deficient group (11.1 ± 2.6%; P < 0.05). In contrast, kidney hypertrophy was exaggerated in the Tp−/− mice compared with controls (37.1 ± 5.4 vs. 12.3 ± 2.3%; P < 0.01). Moreover, the severity of glomerulosclerosis, tubule vacuolization, and interstitial chronic inflammation was also enhanced in the Tp−/− group ( P < 0.01). Thus, in l-NAME hypertension, TP receptors contribute to elevated blood pressure and cardiac hypertrophy. In this model, TP receptors also provided unexpected protection against kidney injury.

scholarly journals Croton schiedeanus Schltd prevents experimental hypertension in rats induced by nitric oxide deficit

2013 ◽  
Vol 49 (4) ◽  
pp. 865-871
Author(s):  
María Teresa Páez ◽  
Diana Catalina Rodríguez ◽  
Daniel Fernando López ◽  
Jorge Arturo Castañeda ◽  
Diana Marcela Buitrago ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Systolic Arterial Pressure ◽  
Control Group ◽  
Experimental Hypertension ◽  
Blank Group ◽  
Mean Values ◽  
Etoh Extract ◽  
Arterial Blood ◽  
Synthase Inhibitor

Croton schiedeanus Schltd (N.V.: "almizclillo") is a plant used in traditional medicine as an antihypertensive in Colombia. It contains flavonoid, diterpenoid and fenilbutanoid metabolites that have vasodilatation effects linked to the NO/cGMP pathway. This work aimed to assess the capacity of a 96% EtOH extract to prevent the hypertension induced by nitric oxide (NO) deficiency in rats. The NO synthase inhibitor L-NAME (10 mg/kg/d, i.p) was administered during five weeks to three groups of rats (6-7 animals): C. Schiedeanus (200 mg/kg/d, p.o), enalapril (reference, 10 mg/kg/d, p.o) and vehicle (control: olive oil 1 ml/kg/d, p.o). In addition, the blank group received only vehicle. The arterial blood pressure (BP) and heart rate (HR) were measured daily for six weeks. After sacrificing the animals, the aortic rings were isolated, contraction was triggered with phenylephrine (PE 10-6 M) and relaxant responses were achieved with cumulative concentrations of acetylcholine (ACh, 10-10 - 10-4 M). L-NAME increased the systolic arterial pressure in the control group, attaining mean values of 131 mm Hg at week 5, whereas the C. schiedeanus, enalapril and blank groups maintained blood pressure under 100 mm Hg. The capacity of PE to contract aortic rings was greater in the C. schiedeanus, enalapril and blank groups than in the control group (2157, 2005, 1910 and 1646 mg, respectively). The pEC50 values for ACh were as follows: C. Schiedeanus (6.89) >enalapril (6.39) > blank (5.68) > control (5.09). These results give support to C. Schiedeanus as a natural antihypertensive source.

Nitric oxide does not mediate autoregulation of retinal blood flow in newborn pig

1995 ◽  
Vol 269 (3) ◽  
pp. H1065-H1072 ◽  
Author(s):  
J. M. Gidday ◽  
Y. Zhu
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Retinal Blood Flow ◽  
Nitric Oxide Synthase Inhibitor ◽  
Arterial Blood ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Arteriolar Diameter ◽  
Retinal Arteriolar ◽  
Retinal Arteriolar Diameter

Isoflurane-anesthetized newborn pigs were used to test the hypothesis that nitric oxide mediates autoregulatory dilations of retinal arterioles. Fundus images were monitored by videomicroscopy at x310, and stimulus-induced changes in retinal arteriolar diameter were measured by on-line image analysis. Dilatative responses to systemic hypoxia (arterial O2 tension 20-30 mmHg), hypotension (mean arterial blood pressure 40 mmHg), or hypercapnia (arterial CO2 tension 70-85 mmHg) were assessed after intravitreal microsuffusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) over the observed arterioles. Twenty-five nanomoles L-NMMA constricted arterioles by 24 +/- 2% (P < 0.01; n = 17 pigs); a significant constriction (14 +/- 2%) was still observed 80 min after drug administration (n = 5). Complete nitric oxide synthase inhibition at this dose was indicated by the findings that co-administration of 2.5 mumol L-arginine reversed this constriction within 17 +/- 2 min (n = 3), that L-NMMA, but not D-NMMA, completely inhibited the 20 +/- 3% P < 0.01) arteriolar dilation induced by intravitreal acetylcholine (7.5 nmol; n = 4), and that no additional constriction was evidenced after administration of a 10-fold greater concentration of L-NMMA (n = 8). However, despite the prominent arteriolar constriction induced by L-NMMA under baseline conditions, increases in retinal arteriolar diameter still occurred in response to hypoxia (n = 5), hypotension (n = 4), or hypercapnia (n = 5) in animals pretreated with 50 nmol L-NMMA; these responses did not differ significantly from arteriolar dilations observed in untreated control animals (n = 16) subjected to the same stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Inhibition of Nitric Oxide Synthesis: Effects on Cerebral Blood Flow and Glucose Utilisation in the Rat

1993 ◽  
Vol 13 (6) ◽  
pp. 985-992 ◽  
Author(s):  
I. M. Macrae ◽  
D. A. Dawson ◽  
J. D. Norrie ◽  
J. McCulloch
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Arterial Blood Pressure ◽  
Bolus Administration ◽  
Nitric Oxide Synthesis ◽  
Conscious Rat ◽  
Nitric Oxide Synthase Inhibitor ◽  
Glucose Utilisation ◽  
Arterial Blood

The consequences of inhibition of nitric oxide synthesis on local CBF and glucose utilisation have been studied in the conscious rat using the specific nitric oxide synthase inhibitor Ng-nitro-l-arginine methyl ester (l-NAME; 30 mg kg−1 i.v.). Local CBF and glucose utilisation were assessed with the [14C]iodoantipyrine and the 2-deoxy-d-[14C]glucose autoradiographic techniques, respectively. l-NAME induced prolonged (>3 h) reductions in local CBF throughout the CNS with concomitant increases in arterial blood pressure. For example, 1 h post l-NAME, CBF dropped from 79 ± 4 to 45 ± 1 ml 100 g−1 min−1 in cerebellum, from 76 ± 4 to 47 ± 2 ml 100 g−1 min−1 in medulla oblongata, and from 117 ± 6 to 72 ± 2 ml 100 g−1 min−1 in cortex. l-NAME produced sustained elevations (e.g., 46 ± 2 mm Hg at 1 h after bolus administration) in mean arterial blood pressure throughout the period evaluated. Despite evidence implicating nitric oxide in neuronal signalling, l-NAME did not significantly influence CNS functional activity, as measured by local rates of glucose utilisation, in any neuroanatomical region examined. Consequently, the normal ratio of blood flow to glucose use throughout the brain was significantly reduced in the presence of l-NAME, although the hierarchy of blood flow levels in different neuroanatomical regions was preserved. These results are consistent with the involvement of nitric oxide in the tonic control of cerebral tissue perfusion.

Delayed cardioprotective effects of exercise in dogs are aminoguanidine sensitive: possible involvement of nitric oxide

2002 ◽  
Vol 102 (4) ◽  
pp. 435-445 ◽  
Author(s):  
László BABAI ◽  
Zsolt SZIGETI ◽  
James R. PARRATT ◽  
Ágnes VÉGH
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Tissue Blood Flow ◽  
Nitric Oxide Synthase Inhibitor ◽  
Arterial Blood ◽  
Ischaemia Reperfusion ◽  
Synthase Inhibitor

Dogs were subjected to exercise on a treadmill, using a protocol in which the speed and slope were increased every 3min, and which elevated both heart rate (to a mean of 198±14beatsċmin-1) and mean arterial blood pressure (to 150±4mmHg). Then, 24 or 48h later, the dogs were anaesthetized with a mixture of α-chloralose and urethane and subjected to a 25min occlusion of the left anterior descending coronary artery. The control dogs (instrumented but not exercised) were subjected to the same procedure. In some dogs the nitric oxide synthase inhibitor aminoguanidine (50mgċkg-1; intravenous) was administered 30min before occlusion. Baroreflex sensitivity (BRS) was determined by the rapid bolus injection of phenylephrine 60min before, and again 3min after, the onset of occlusion. Exercise markedly reduced the consequences of coronary artery occlusion 24h (but not 48h) later, without modifying myocardial tissue blood flow. In the exercised dogs there were reductions in arrhythmia severity [ventricular fibrillation (VF) during occlusion, 0%; survival from the combined ischaemia/reperfusion insult, 70%] compared with controls (VF during occlusion, 36%; survival, 9%). BRS was preserved during occlusion in the exercised dogs (before occlusion, 1.60±0.54msċmmHg-1; 3min after occlusion, 1.37±0.4msċmmHg-1), but not in controls (before occlusion, 1.28±0.29msċmmHg-1; 3min after occlusion, 0.45±0.12msċmmHg-1; P < 0.05), and other ischaemic changes (inhomogeneity of electrical activation and changes in the ST-segment, recorded over the ischaemic region) were also less marked in the exercised dogs. Exercise-induced cardioprotection was abolished by aminoguanidine (VF during occlusion, 25%; survival, 0%). The results show that even a single period of exercise affords delayed protection against ischaemia/reperfusion-induced VF and other ischaemic changes. Since this protection is abolished by aminoguanidine, and since (inducible) NO synthase activity was elevated 3-fold in left ventricular samples 24h after exercise, we suggest that this protection is mediated by nitric oxide.

scholarly journals Effects of Inhibition of Nitric Oxide Synthase on Muscular Arteries During Exercise: Nitric Oxide Does Not Contribute to Vasodilation During Exercise or in Recovery

2020 ◽  
Vol 9 (16) ◽  
Author(s):  
Kevin O'Gallagher ◽  
Husain Shabeeh ◽  
Shahzad Munir ◽  
Ali Roomi ◽  
Benyu Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Cardiac Output ◽  
Femoral Artery ◽  
Peripheral Resistance ◽  
Muscular Artery ◽  
Arterial Blood ◽  
Exercise Hemodynamics ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Background Basal release of nitric oxide ( NO ) from the vascular endothelium regulates the tone of muscular arteries and resistance vasculature. Effects of NO on muscular arteries could be particularly important during exercise when shear stress may stimulate increased NO synthesis. Methods and Results We investigated acute effects of NO synthase inhibition on exercise hemodynamics using N G ‐monomethyl‐ l ‐arginine ( l ‐ NMMA ), a nonselective NO synthase ‐inhibitor. Healthy volunteers (n=10, 5 female, 19–33 years) participated in a 2‐phase randomized crossover study, receiving l ‐ NMMA (6 mg/kg, iv over 5 minutes) or placebo before bicycle exercise (25–150 W for 12 minutes). Blood pressure, cardiac output (measured by dilution of soluble and inert tracers) and femoral artery diameter were measured before, during, and after exercise. At rest, l ‐ NMMA reduced heart rate (by 16.2±4.3 bpm relative to placebo, P <0.01), increased peripheral vascular resistance (by 7.0±1.4 mmHg per L/min, P <0.001), mean arterial blood pressure (by 8.9±3.5 mmHg, P <0.05), and blunted an increase in femoral artery diameter that occurred immediately before exercise (change in diameter: 0.14±0.04 versus 0.32±0.06 mm after l ‐ NMMA and placebo, P <0.01). During/after exercise l ‐ NMMA had no significant effect on peripheral resistance, cardiac output, or on femoral artery diameter. Conclusions These results suggest that NO plays little role in modulating muscular artery function during exercise but that it may mediate changes in muscular artery tone immediately before exercise.

scholarly journals Effect of cross-linked hemoglobin transfusion on endothelial-dependent dilation in cat pial arterioles

1998 ◽  
Vol 275 (4) ◽  
pp. H1313-H1321 ◽  
Author(s):  
Yoshio Asano ◽  
Raymond C. Koehler ◽  
John A. Ulatowski ◽  
Richard J. Traystman ◽  
Enrico Bucci
Keyword(s):  
Nitric Oxide ◽  
Hemoglobin Concentration ◽  
Nitric Oxide Donor ◽  
Nitric Oxide Synthase Inhibitor ◽  
Cranial Window ◽  
Dilatory Response ◽  
Pial Arterioles ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Arteriolar Diameter

We determined whether addition of hemoglobin to the plasma would inhibit endothelial-dependent dilation in brain where tight endothelial junctions limit hemoglobin extravasation. Pial arteriolar diameter was measured by intravital microscopy through closed cranial windows in anesthetized cats either without transfusion (hematocrit = 32%) or after exchange transfusion with an albumin or sebacyl-cross-linked human hemoglobin solution (hematocrit = 18%). Dilation of small, medium, and large arterioles to acetylcholine and ADP was not significantly altered by hemoglobin transfusion. The dilatory responses were inhibited by the nitric oxide synthase inhibitor N G-nitro-l-arginine, although significant dilation to 30 μM acetylcholine persisted in small arterioles in the control and albumin-transfused group but not in the hemoglobin-transfused group. The dilatory response to the nitric oxide donor 3-morpholinosydnonimine was unaffected by albumin or hemoglobin transfusion, but the response to nitroprusside was reduced by one-third after hemoglobin transfusion. When cross-linked hemoglobin was superfused through the cranial window, the acetylcholine response became inhibited at a hemoglobin concentration of 0.1 μM and was completely blocked at 10 μM. Because this concentration is substantially less than the 500 μM hemoglobin concentration in plasma after transfusion when there was no inhibition of the acetylcholine response, hemoglobin permeation of the blood-brain barrier was considered negligible. We conclude that exchange of red cell-based hemoglobin with plasma-based hemoglobin does not produce a more effective sink for endothelial-derived nitric oxide evoked by agonist receptor-mediated activation. Furthermore, decreased hematocrit does not affect agonist-evoked endothelial-dependent dilation.

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