Nitric Oxide Modulation of Coronary Artery Myogenic Tone in Spontaneously Hypertensive and Wistar—Kyoto Rats

1998 ◽  
Vol 94 (3) ◽  
pp. 225-229 ◽  
Author(s):  
Susana R. Garcia ◽  
Stuart J. Bund
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Coronary Arteries ◽  
Myogenic Tone ◽  
Internal Diameter ◽  
Nitric Oxide Synthase Inhibitor ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Wistar Kyoto ◽  
Synthase Inhibitor

1. The endothelium contributes substantially to the modulation of myogenic tone in coronary arteries from spontaneously hypertensive rats (SHR) and Wistar—Kyoto rats (WKY). This study has addressed the contributions of endothelium-derived nitric oxide and cyclo-oxygenase products to this modulation in small coronary arteries (approximately 200 μm internal diameter) from 20-week-old SHR and WKY under pressurized, no-flow conditions in an arteriograph. 2. Active pressure—diameter relationships were uninfluenced by the cyclo-oxygenase inhibitor indomethacin (10 μmol/l) in either rat strain. In the presence of indomethacin and the nitric oxide synthase inhibitor Nω-nitro-l-arginine (l-NNA, 0.1 mmol/l), coronary arteries from SHR and WKY generated significantly greater myogenic tone. This increase in tone was similar in both strains. 3. In endothelium-denuded arteries, indomethacin and l-NNA did not influence tone. 4. Therefore, these results demonstrate that endothelium-derived nitric oxide is basally released to attenuate SHR and WKY coronary artery myogenic tone, whereas endothelium-derived cyclo-oxygenase products have no net vasoactive influence. Additionally, these data suggest that basal nitric oxide-mediated relaxation is normal in SHR coronary arteries and is therefore unlikely to be a pathogenic mechanism in this animal model of hypertension.

scholarly journals Magnesium causes nitric oxide independent coronary artery vasodilation in humans

Heart ◽  
2001 ◽  
Vol 86 (2) ◽  
pp. 212-216
Author(s):  
H Teragawa ◽  
M Kato ◽  
T Yamagata ◽  
H Matsuura ◽  
G Kajiyama
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Coronary Artery ◽  
Coronary Blood Flow ◽  
Coronary Arteries ◽  
Quantitative Coronary Angiography ◽  
University Hospital ◽  
Nitric Oxide Synthase Inhibitor ◽  
Before And After ◽  
Synthase Inhibitor

OBJECTIVETo determine how magnesium affects human coronary arteries and whether endothelium derived nitric oxide (EDNO) is involved in the coronary arterial response to magnesium.DESIGNQuantitative coronary angiography and Doppler flow velocity measurements were used to determine the effects of the nitric oxide synthase inhibitorNG-monomethyl-L-arginine (L-NMMA) on magnesium induced dilation of the epicardial and resistance coronary arteries.SETTINGHiroshima University Hospital a tertiary cardiology centre.PATIENTS17 patients with angiographically normal coronary arteries.INTERVENTIONSMagnesium sulfate (MgSO4) (0.02 mmol/min and 0.2 mmol/min) was infused for two minutes into the left coronary ostium before and after intracoronary infusion of L-NMMA.MAIN OUTCOME MEASURESDiameter of the proximal and distal segments of the epicardial coronary arteries and coronary blood flow.RESULTSAt a dose of 0.02 mmol/min, MgSO4 did not affect the coronary arteries. At a dose of 0.2 mmol/min, MgSO4 caused coronary artery dilation (mean (SEM) proximal diameter 3.00 (0.09) to 3.11 (0.09) mm; distal 1.64 (0.06) to 1.77 (0.07) mm) and increased coronary blood flow (79.3 (7.5) to 101.4 (9.9) ml/min, p < 0.001 vbaseline for all). MgSO4 increased the changes in these parameters after the infusion of L-NMMA (p < 0.001v baseline).CONCLUSIONSMagnesium dilates both the epicardial and resistance coronary arteries in humans. Furthermore, the coronary arterial response to magnesium is dose dependent and independent of EDNO.

Influence of Mode of Contraction on the Mechanism of Acetylcholine-Mediated Relaxation of Coronary Arteries from Normotensive and Spontaneously Hypertensive Rats

1998 ◽  
Vol 94 (3) ◽  
pp. 231-238 ◽  
Author(s):  
Stuart J. Bund
Keyword(s):  
Coronary Arteries ◽  
Spontaneously Hypertensive Rats ◽  
Statistical Significance ◽  
Myogenic Tone ◽  
Internal Diameter ◽  
Flow Conditions ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Endothelium Dependent Relaxation

1. Endothelium-dependent acetylcholine-mediated relaxations of small coronary arteries (∼200 μm internal diameter) from 20 weeks old spontaneously hypertensive rats (SHR) and normotensive Wistar—Kyoto (WKY) controls were compared under pressurized no-flow conditions after the development of myogenic tone or constriction with the thromboxane A2 mimetic U46619. 2. Relaxations of WKY and SHR arteries following development of myogenic tone did not differ and were not significantly influenced by indomethacin alone (10 μmol/l) or in combination with Nω-nitro-l-arginine (l-NNA, 0.1 mmol/l). Maximum relaxations were significantly attenuated by 30 mmol/l K+ in the SHR, from 85 ± 7% (n = 11) to 20 ± 8% (n = 8), P < 0.001, and in the WKY from 86 ± 5% (n = 9) to 39 ± 14% (n = 8), P < 0.01. 3. Relaxations following constriction with U46619 were also similar in both rat strains. Maximum relaxations were 50 ± 11% (n = 8) in SHR and 60 ± 7% (n = 6) in WKY. Indomethacin did not influence these relaxations. The combination of indomethacin and l-NNA attenuated relaxations in WKY (P < 0.01), but in the SHR the attenuation did not achieve statistical significance (P = 0.07) compared with controls; the maximum responses were reduced to 25 ± 7% (n = 8) and 14 ± 11% (n = 6) in the SHR and WKY respectively, but only in the WKY was this reduction significant (P < 0.05). 4. These data demonstrate that, under control conditions, SHR and WKY coronary arteries relax equally effectively, regardless of mode of contraction, and also that the mechanism of acetylcholine-mediated relaxation differs according to the mode of contraction. Acetylcholine relaxes myogenic tone by a K+-sensitive mechanism in both WKY and SHR, consistent with a role for endothelium-derived hyperpolarizing factor; NO contributes substantially to the relaxation of U46619-induced tone by acetylcholine in the WKY, but to a diminished extent in the SHR. 5. These data indicate that the choice of vasoconstrictor agent is of critical concern when assessing mechanisms of endothelium-dependent relaxation and abnormalities thereof in hypertension.

Contribution of Vascular Nitric Oxide to Basal Blood Pressure in Conscious Spontaneously Hypertensive Rats and Normotensive Wistar Kyoto Rats

1995 ◽  
Vol 89 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Naoyoshi Minami ◽  
Yutaka Imai ◽  
Jun-Ichiro Hashimoto ◽  
Keishi Abe
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Methyl Ester ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Basal Blood Pressure ◽  
Wistar Kyoto

1. The aim of this study was to clarify the extent to which vascular nitric oxide contributes to basal blood pressure in conscious spontaneously hypertensive rats and normotensive Wistar Kyoto rats. 2. The contribution of vascular nitric oxide to maintenance of blood pressure was estimated by measuring the pressor response to an intravenous injection of nitric oxide synthase inhibitor, Nω-l-arginine methyl ester, given after serial injections of captopril, vasopressin V1-receptor antagonist (V1-antagonist) and ganglion blocker (pentolinium) in conscious spontaneously hypertensive and Wistar Kyoto rats aged 20–28 weeks. To estimate the ‘amplifier property’ of hypertrophied vasculature in spontaneously hypertensive rats, which is known to modulate pressor responses, the lower blood pressure plateau after serial injections of captopril, V1-antagonist and pentolinium and the maximum blood pressure elicited by subsequent injection of increasing doses of phenylephrine were also measured. 3. The serial injections of captopril, V1-antagonist and pentolinium decreased mean arterial pressure from 164 ± 9 mmHg to 67 ± 2 mmHg and from 117 ± 2 mmHg to 49 ± 1 mmHg in spontaneously hypertensive and Wistar Kyoto rats respectively. The subsequent injection of Nω-l-arginine methyl ester restored mean arterial pressure almost to its control levels in both spontaneously hypertensive and Wistar Kyoto rats. The absolute changes in mean arterial pressure elicited by Nω-l-arginine methyl ester were significantly greater in spontaneously hypertensive than in Wistar Kyoto rats (P < 0.01), but there was no significant difference in the responses to Nω-l-arginine methyl ester when they were expressed as percentages of either the lower blood pressure plateau or maximum blood pressure. 4. These results indicate that basal blood pressure in both spontaneous hypertensive and Wistar Kyoto rats is maintained by a balance between vascular nitric oxide and major pressor systems. They also suggest that the vasodilatory effect of vascular nitric oxide does not differ between spontaneously hypertensive and Wistar Kyoto rats, and that the increased pressor effect of Nω-l-arginine methyl ester in spontaneously hypertensive rats is due to a vascular amplifier mechanism.

scholarly journals Contractile responsiveness of coronary arteries from exercise-trained rats

1997 ◽  
Vol 83 (2) ◽  
pp. 434-443 ◽  
Author(s):  
Janet L. Parker ◽  
Mildred L. Mattox ◽  
M. Harold Laughlin
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Nitric Oxide Synthase ◽  
Exercise Training ◽  
Sodium Nitroprusside ◽  
Coronary Arteries ◽  
Internal Diameter ◽  
Relaxation Responses ◽  
Proximal Coronary Artery ◽  
Oxide Synthase

Parker, Janet L., Mildred L. Mattox, and M. Harold Laughlin.Contractile responsiveness of coronary arteries from exercise trained rats. J. Appl. Physiol. 83(2): 434–443, 1997.—The purpose of this study was to determine whether exercise training alters vasomotor reactivity of rat coronary arteries. In vitro isometric microvessel techniques were used to evaluate vasomotor properties of proximal left anterior artery rings (1 ring per animal) from exercise-trained rats (ET; n = 10) subjected to a 12-wk treadmill training protocol (32 m/min, 15% incline, 1 h/day, 5 days/wk) and control rats (C; n = 6) restricted to cage activity. No differences in passive length-tension characteristics or internal diameter (158 ± 9 and 166 ± 9 μm) were observed between vessesls of C and ET rats. Concentration-response curves to K+ (5–100 mM), prostaglandin F2α(10−8–10−4M), and norepinephrine (10−8–10−4) were unaltered ( P > 0.05) in coronary rings from ET rats compared with C rats; however, lower values of the concentration producing 50% of the maximal contractile response in rings from ET rats ( P = 0.05) suggest that contractile sensitivity to norepinephrine was enhanced. Vasorelaxation responses to sodium nitroprusside (10−9-10−4M) and adenosine (10−9-10−4M) were not different ( P > 0.05) between vessels of C and ET rats. However, relaxation responses to the endothelium-dependent vasodilator acetylcholine (ACh; 10−10-10−4M) were significantly blunted ( P < 0.001) in coronary rings from ET animals; maximal ACh relaxation averaged 90 ± 5 and 46 ± 12%, respectively, in vessels of C and ET groups. In additional experiments, two coronary rings (proximal and distal) were isolated from each C ( n = 7) and ET ( n = 7) animal. Proximal coronary artery rings from ET animals demonstrated decreased relaxation responses to ACh; however, ACh-mediated relaxation of distal coronary rings was not different between C and ET groups. N G-monomethyl-l-arginine (inhibitor of nitric oxide synthase) blocked ACh relaxation of all rings. l-Arginine (substrate for nitric oxide synthase) did not improve the blunted ACh relaxation in proximal coronary artery rings from ET rats. These studies suggest that exercise-training selectively decreases endothelium-dependent (ACh) but not endothelium-independent (sodium nitroprusside) relaxation responses of rat proximal coronary arteries; endothelium-dependent relaxation of distal coronary arteries is unaltered by training.

Does a general alteration in nitric oxide synthesis system occur in spontaneously hypertensive rats?

1994 ◽  
Vol 266 (1) ◽  
pp. H272-H278 ◽  
Author(s):  
J. Xiao ◽  
P. K. Pang
Keyword(s):  
Nitric Oxide ◽  
Spontaneously Hypertensive Rats ◽  
No Synthase ◽  
Hypertensive Rats ◽  
Synthesis System ◽  
Spontaneously Hypertensive ◽  
Proliferation Of Lymphocytes ◽  
General Activation ◽  
Wistar Kyoto ◽  
Synthase Inhibitor

Immune dysfunction has been reported in spontaneously hypertensive rats (SHR). The current study investigated interactions between macrophages or vascular smooth muscle cells (VSMC) and lymphocytes in SHR and examined the role of nitric oxide (NO) in this interaction. SHR macrophages significantly inhibited the proliferation of lymphocytes from SHR and the genetic control, Wistar-Kyoto rats (WKY). This inhibition was reversed by a NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA). SHR VSMC also significantly inhibited the proliferation responses of lymphocytes from SHR and WKY. The inhibition was cell density dependent. In addition, L-NMMA fully reversed the inhibition by SHR VSMC. Upon stimulation, the macrophages and VSMC from SHR produced a significantly higher amount of NO compared with those from WKY. These results suggest that the overproduction of NO was involved in the interaction between macrophages or VSMC and lymphocytes in SHR. Increased NO synthase activity in macrophages and VSMC may indicate a general activation of the NO synthesis system in SHR. The alteration of the NO synthesis system may be an important factor contributing to the lymphocyte depression in hypertension.

Nitric Oxide Synthase Inhibitor in the Hypothalamus of the Spontaneously Hypertensive Rat (SHR)

1996 ◽  
Vol 90 (s34) ◽  
pp. 3P-3P
Author(s):  
J Alaghband-Zadeh ◽  
I Das ◽  
S Mehdizadeh ◽  
NS Khan ◽  
J De Belleroche ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Spontaneously Hypertensive Rat ◽  
Nitric Oxide Synthase Inhibitor ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Synthase Inhibitor ◽  
Oxide Synthase

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.

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