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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. To elucidate the pathophysiologic role of vascular natriuretic peptide (NP) receptor in hypertension, we determined NP-A and NP-B receptor mRNA levels by means of ribonuclease protection assay in aorta of three types of hypertensive rats. 2. The NP-A receptor mRNA level was higher in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) and deoxycorticosterone acetate-salt hypertensive rats than that in their respective control rats. On the contrary, the NP-A receptor mRNA level was lower in NG-nitro-L-arginine-methyl ester (L-NAME)-induced hypertensive rats compared with that in the control. 3. The NP-B receptor mRNA level did not show any significant change in all three hypertensive rats compared with their respective controls. 4. The present study suggests that high blood pressure is not the major factor regulating the NP receptor gene expression and also that the receptor subtype is independently regulated from each other.
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PMID:Gene expression of vascular natriuretic peptide receptor in the aorta of hypertensive rats. 907 44

We examined the hypothesis that activity of Ca2+-dependent K+ channels is increased in the basilar artery during chronic hypertension. Diameter of the basilar artery was measured using a cranial window in anesthetized normotensive Wistar-Kyoto rats (WKY, arterial pressure = 109 +/- 3 mmHg, mean +/- SE) and stroke-prone spontaneously hypertensive rats (SHRSP, arterial pressure = 179 +/- 4 mmHg). Responses of the basilar artery to topical application of tetraethylammonium ion (TEA), an inhibitor of Ca2+-dependent K+ channels, were examined in WKY and SHRSP. Vessel diameter decreased by 2 +/- 1 and 4 +/- 0.1% in WKY and by 7 +/- 2 and 18 +/- 1% in SHRSP (P < 0.05 vs. WKY) in response to 10(-4) and 10(-3) M TEA, respectively. Similar results were obtained using iberiotoxin (10(-8) and 10(-7) M), a highly selective inhibitor of Ca2+-dependent K+ channels. In contrast to constrictor responses to TEA and iberiotoxin, constrictor responses of the basilar artery in response to serotonin and U-46619 were similar in WKY and SHRSP. In WKY rats that were made chronically hypertensive (arterial pressure = 172 +/- 6 mmHg) after treatment for 4 wk with N(G)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, constriction of the basilar artery in response to TEA was also enhanced. These findings suggest that activity of Ca2+-dependent K+ channels is enhanced in the basilar artery in vivo in two models of chronic hypertension. Thus Ca2+-dependent K+ channels in the basilar artery may be activated during chronic hypertension, perhaps as a response to elevation of intracellular concentration of Ca2+.
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PMID:Functional activity of Ca2+-dependent K+ channels is increased in basilar artery during chronic hypertension. 908 3

Nitric Oxide (NO) has been implicated as a mediator of neuronal injury in vascular stroke. On the other hand, NO is suggested to play a neuroprotective role by increasing blood flow during cerebral ischemia. In order to evaluate the role of NO in the spinal cord ischemia, effects of nitric oxide synthase (NOS) inhibition on the recovery of reflex potentials after a transient spinal cord ischemia were examined in urethane-chloralose anesthetized spinal cats. Spinal cord ischemia was produced by occlusion of the thoracic aorta and the both internal mammary arteries for 10 min. Regional blood flow (RBF) in the spinal cord was continuously measured with a laser-Doppler flow meter. The monosynaptic (MSR) and polysynaptic reflex (PSR) potentials elicited by electrical stimulation of the tibial nerve, were recorded from the L7 or S1 ventral root. The recovery process of spinal reflex potentials was reproducible when the oclusion was repeated twice at an interval of 120 min. Pretreatment with N(G)-monomethyl-L-arginine (L-NMMA, 10 mg/kg), a NOS inhibitor significantly accelerated the recovery of PSR potentials after spinal cord ischemia. The accelerating effect of L-NMMA on the recovery of PSR potentials was abolished by co-administration of L-arginine (1 mg/kg/min) but not by that of D-arginine (1 mg/kg/min). L-NMMA failed to improve RBF in the spinal cord during ischemia and reperfusion. Nitroprusside (10 microg/kg/min), a NO donor, retarded the recovery of PSR potentials after spinal cord ischemia. These results suggest that NO production has a significant influence on the functional recovery after transient spinal cord ischemia.
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PMID:Inhibition of nitric oxide synthesis accelerates the recovery of polysynaptic reflex potentials after transient spinal cord ischemia in cats. 910 59

1. The acute effects of nitric oxide synthase inhibition on the haemodynamics in stroke-prone spontaneously hypertensive (SHRSP) and normotensive Wistar-Kyoto (WKY) rats were investigated using radiolabelled microspheres. 2. Intravenous administration of 3 and 6 mg/kg NG-nitro-L-arginine (L-NNA) caused a significant increase in total peripheral resistance, a decrease in cardiac output and an increase in blood pressure in both SHRSP and WKY rats. 3. Significant decreases in regional blood flow (RBF) in the lung, muscle and stomach of WKY rats were observed following L-NNA administration. 4. NG-nitro-L-arginine produced a 70% increase in brain regional blood flow at a dose of 6 mg/kg only in SHRSP. 5. There was a variation in the involvement of nitric oxide (NO) in different tissues. 6. It is concluded that hypertension in SHRSP augments NO-mediated vasodilation.
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PMID:Tissue variation of acute haemodynamic changes by NG-nitro-L-arginine in stroke-prone spontaneously hypertensive and Wistar-Kyoto rats. 913 Dec 93

1. To observe the effect of nitric oxide (NO) on the myocardium, the NO synthesis inhibitor NG-nitro-L-arginine (L-NNA) was administered to hypercholesterolaemic stroke-prone spontaneously hypertensive (SHRSP) rats. 2. Hypercholesterolaemic SHRSP were produced by feeding SHRSP a high fat and high cholesterol diet (HFC) for 2 weeks. The rats were then divided into three groups: (i) the N group, which were fed the HFC diet containing 0.023% L-NNA and 1% NaCl in their drinking water (n = 10); (ii) the NH group, which were fed the HFC diet containing 0.023% L-NNA and 1% NaCl in their drinking water which also contained 80 mg/L hydralazine (n = 10); and (iii) the C group, which were fed the HFC diet and 1% NaCl in their drinking water (n = 10). 3. All rats in the N and NH groups died within 35 days of the initiation of L-NNA administration. Rats in the N and NH groups had significantly increased serum creatine phosphokinase, lactate dehydrogenase, glutamic oxaloacetic transaminase and serum total cholesterol levels compared with rats in the C group. 4. Fibrosis in response to necrosis was histopathologically observed in the hearts of all rats in the N and NH groups without exception. Occlusion or intimal thickening in the arteries adjacent to the necrotic regions was also observed. 5. These results suggest that nitric oxide deficiency induces myocardial infarction in hypercholesterolaemic SHRSP. These NO-deficient hypercholesterolaemic SHRSP offer a new model of myocardial infarction in rats.
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PMID:Nitric oxide deficiency induces myocardial infarction in hypercholesterolaemic stroke-prone spontaneously hypertensive rats. 914 85

Clinical states associated with nitric oxide deficiency are often accompanied by vasoconstriction. We studied the effects of prolonged infusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on systemic and renal hemodynamics in humans and the reversibility of the established vasoconstriction by calcium channel blockade with nifedipine. Seven healthy men underwent three 7-hour clearance studies. During one study, L-NMMA (3 mg/kg priming dose plus 3 mg.kg-1.h-1) was infused during hours 2 through 5, and during another study, nifedipine (0.015 mg/kg priming dose plus 0.015 mg.kg-1.h-1) was coinfused during hours 4 and 5. A third study served as time control. L-NMMA elicited reproducible systemic and renal vasoconstriction that was stable during the 4 hours of infusion. Systemic vascular resistance index, calculated from bioimpedance-derived cardiac index, increased from 22 +/- 1 to 29 +/- 2 mm Hg.min.m2.L-1 (P < .05). Mean arterial pressure rose by 4 +/- 1 mm Hg (P < .05), and heart rate, stroke index, and cardiac index decreased. Renal blood flow, calculated from renal plasma flow, decreased from 1182 +/- 101 to 785 +/- 53 mL/min, and renal vascular resistance increased from 73 +/- 5 to 115 +/- 6 mm Hg.min.L-1 (P < .05). Glomerular filtration rate decreased from 114 +/- 6 to 104 +/- 6 mL/min (P < .05), and filtration fraction increased. Sodium excretion fell from 89 +/- 9 to 32 +/- 7 mumol/min (P < .05). Nifedipine completely reversed systemic vasoconstriction. Nifedipine caused partial restoration of renal vascular resistance and complete normalization of glomerular filtration rate and sodium excretion but left the elevated filtration fraction unaltered. We conclude that sustained nitric oxide deficiency in humans is accompanied by strong systemic and renal vasoconstriction, decreased glomerular filtration rate, and sodium retention. Nifedipine can reverse most of these effects, suggesting a role for calcium channel blockade in pathological states of impaired nitric oxide activity.
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PMID:Nifedipine attenuates systemic and renal vasoconstriction during nitric oxide inhibition in humans. 914 86

The etiology of stroke in sickle cell disease is unclear, but may involve abnormal red blood cell (RBC) adhesion to the vascular endothelium and altered vasomotor tone regulation. Therefore, we examined both the adhesion of sickle (SS)-RBCs to cerebral microvessels and the effect of SS-RBCs on cerebral blood flow when the nitric oxide (NO) pathway was inhibited. The effect of SS-RBCs was studied in the rat cerebral microcirculation using either a cranial window for direct visualization of infused RBCs or laser Doppler flowmetry (LDF) to measure RBC flow. When fluorescently labeled human RBCs were infused into rats, SS-RBCs had increased adhesion to rat cerebral microvessels compared with control AA-RBCs (P = .01). Next, washed SS-RBCs or AA-RBCs were infused into rats prepared with LDF probes after pretreatment (40 mg/kg intravenously) with the NO synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), or the control isomer, D-NAME. In 9 rats treated with systemic L-NAME and SS-RBCs, 5 of 9 experienced a significant decrease in LDF and died within 30 minutes after the RBC infusion (P = .0012). In contrast, all control groups completed the experiment with stable LDF and hemodynamics. Four rats received a localized superfusion of L-NAME (1 mmol/L) through the cranial window followed by infusion of SS-RBCs. Total cessation of flow in all observed cerebral microvessels occurred in 3 of 4 rats within 15 minutes after infusion of SS-RBCs. We conclude that the NO pathway is critical in maintaining cerebral blood flow in the presence of SS-RBCs in this rat model. In addition, the enhanced adhesion of SS-RBCs to rat brain microvessels may contribute to cerebral vaso-occlusion either directly, by disrupting blood flow, or indirectly, by disturbing the vascular endothelium.
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PMID:Mechanisms of stroke in sickle cell disease: sickle erythrocytes decrease cerebral blood flow in rats after nitric oxide synthase inhibition. 919 84

Although nitric oxide (NO) has been shown to play an important role in the pathophysiology of cerebral ischemia, its contribution to the pathogenesis of experimentally induced thromboembolic stroke is unknown. In this study, we pharmacologically manipulated NO levels in the acute post-thrombotic stage and determined the effects on behavior and histopathology. The following drugs were used: nitro-L-arginine-methyl ester (L-NAME), a non-specific endothelial and neuronal nitric oxide synthase (eNOS and nNOS) inhibitor, 3-bromo-7-nitroindazole (7-NI), a specific inhibitor for nNOS, the NO precursor, exogenous L-arginine and the NO-donor, 3-morpholino-sydnonimine (SIN-1). Male Wistar rats (n = 76) were randomly assigned to receive vehicle or drug immediately after common carotid artery thrombosis (CCAT). Regional measurements of cortical NOS activity using the [3H]L-arginine to [3H]L-citrulline conversion assay were decreased 1 h after treatment with L-NAME and 7-NI by 50 and 65%, respectively; hippocampal NOS activity was reduced with L-NAME by 35% and with 7-NI by 65%. L-NAME significantly worsened forelimb placing as compared to other groups. 7-NI accelerated sensorimotor recovery. Water maze retention deficits were noted 48 h after CCAT and these were exacerbated by L-NAME treatment. Histopathological protection was conferred in the hippocampus by 7-NI and SIN-1; conversely, L-NAME increased neuronal injury in the contralateral cortex. L-arginine had no effect on these outcomes. In conclusion, both structural and functional consequences of CCAT can be aggravated by limiting endothelial NO production in the acutely post-thrombotic brain. In contrast, inhibition of nNOS and infusion of an NO donor has a beneficial effect on pathology.
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PMID:The role of nitric oxide in the pathophysiology of thromboembolic stroke in the rat. 921 60

1. Isolated basilar arteries from spontaneously hypertensive stroke-prone rats (SHRSP) are more sensitive to the contractile effect of 5-hydroxytryptamine (5-HT) than those from normotensive Wistar Kyoto rats (WKY). This has been attributed to a different proportion of 5-HT receptor subtypes mediating these responses. In the present study we have examined if differences in nitric oxide release could also contribute to this difference in sensitivity to 5-HT. 2. At rest, the normalized internal diameter was significantly smaller in SHRSP (297.4 +/- 3.5 microm, n = 88) than in WKY (375.1 +/- 4.0 microm, n = 62, P<0.01) arteries. The contractile response to 100 mM KCl was higher in WKY (3.57 +/- 0.15 mN mm(-1), n = 22) than in SHRSP arteries (2.32 +/- 0.20 mN mm(-1), n = 28, P<0.01). 3. When added on the plateau of contraction to 5-HT (1 microM), acetylcholine (ACh, 3 microM) evoked significant relaxation in all preparations from WKY (n = 20), but only in 15 out of 26 preparations from SHRSP. The mean relaxations were 55.4 +/- 5.2% in WKY and 20.6 +/- 4.6% in SHRSP (as % of the contractile tone evoked by 5-HT: P<0.01). 4. The NO synthase inhibitor N(omega)-nitro-L-arginine (L-NOARG, 0.1 mM) produced a similar increase in tone in both WKY and SHRSP. This tone was equal (in % of the contractile response to 100 mM KCl) to 70.8 +/- 4.4% in WKY (n = 20) and 67.6 +/- 5.9% in SHRSP (n=26) and was reversed by L-arginine (1 mM) and by 1,4-dihydropyridine calcium channel blockers (10 nM nisoldipine, 10 nM lacidipine, 100 nM nifedipine). The L-NOARG-induced tone was absent when the arteries were bathed in phosphate-free Krebs (pH 7.4). 5. EC50 values of 5-HT were about four fold smaller in SHRSP than in WKY arteries (P<0.01). The maximal response to 5-HT (Emax) was higher than 100 mM KCl-contraction in SHRSP but not in WKY arteries. Removal of endothelium produced a shift to the left of the 5-HT curve in WKY, but not in SHRSP arteries. 6. When evoked in phosphate-free Krebs, the contractile responses to 5-HT showed tachyphylaxis, but the responses were reproducible by adding the agonist at 30 min intervals. In such conditions, EC50 values of 5-HT were about two fold smaller in SHRSP than in WKY arteries (P<0.01). In phosphate-free Krebs, the blockade of NO synthase did not change the contractile response to 100 mM KCl; it reduced EC50 and increased Emax of 5-HT in WKY, but not in SHRSP. 7. These results confirm that the sensitivity to 5-HT is higher in basilar artery isolated from SHRSP than in those from WKY. They show that endothelium-dependent vasorelaxation to ACh is impaired in SHRSP. The finding that removal of endothelium or blockade of NO synthase augmented the contractile response to 5-HT in WKY, but not in SHRSP basilar arteries indicates that the difference in responsiveness to 5-HT observed between WKY and SHRSP basilar arteries might be, at least in part, related to dissimilarities in NO release. Furthermore, the L-NOARG-induced contraction sensitive to calcium channel blockers indicates that, in basilar arteries, NO production might lower L-type calcium channel opening and thereby control the tone of the vessels.
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PMID:Role of nitric oxide in the contractile response to 5-hydroxytryptamine of the basilar artery from Wistar Kyoto and stroke-prone rats. 924 38

Randomized trials of thrombolytic therapy in stroke have reported an improvement in neurologic outcome; however, the addition of aspirin has resulted in a significant increase in mortality and antagonism of clot lysis in clinical and animal studies, respectively. This finding is in contradistinction to the known synergy in mortality reduction for aspirin and thrombolytics in myocardial infarction. It is hypothesized that aspirin antagonism of clot lysis is related to inhibition of nitric oxide (NO) and may be reversed by providing a source of NO. Twenty rabbits were treated with aspirin (20 mg/kg, i.v.) prior to internal carotid clot embolization. One-half hour following embolization, rabbits were randomized to receive vehicle (n = 5), the NO precursor L-arginine (300 mg/kg, i.v. bolus at 0.5 and 2.5 h postembolus; n = 5), or a nitric oxide donor (nitroprusside, 1 mg/kg/h, i.a., or nitroglycerin, 10 microg/kg/min, i.v., n = 5 each agent). Tissue plasminogen activator (t-PA) (6.3 mg/kg) was administered from 1 to 3 h after embolization. Lysis of the tin-tagged clot was followed with serial X rays and gross examination. No rabbit in the control group experienced complete clot lysis. However, 2 of 5 rabbits in the L-arginine group and 6 of 10 rabbits in the nitric oxide donor (nitroprusside and nitroglycerin) groups noted complete clot lysis (P < 0.05, Fisher exact test). Thus, administration of an NO donor (nitroglycerin or nitroprusside) and, to a lesser extent L-arginine, reversed aspirin's antagonism of t-PA thrombolysis. This study may help explain the discrepant results seen with aspirin and thrombolytics.
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PMID:Nitric oxide reverses aspirin antagonism of t-PA thrombolysis in a rabbit model of thromboembolic stroke. 927 62


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