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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro studies have indicated that nitric oxide may play an important role in modulating the renal vascular actions of angiotensin II (Ang II). However, the physiological importance of this interaction in the long-term regulation of renal hemodynamics is unknown. Therefore, the goal of this study was to determine if long-term Ang II-induced renal vasoconstriction was potentiated by nitric oxide synthesis inhibition. The intrarenal effects of Ang II were examined in eight unilaterally nephrectomized, conscious dogs before and after systemic inhibition of nitric oxide synthesis. Ang II infusion into the renal artery at 0.5 ng/kg per minute resulted in decreases in renal plasma flow of 15% and 9% after 3 and 5 days, respectively. During this time, glomerular filtration rate decreased 12% after 3 days of angiotensin but was not significantly changed after 5 days. After 4 days of recovery from Ang II, nitric oxide synthesis was inhibited with intravenous NG-nitro-L-arginine-methyl ester (L-NAME) at 10 micrograms/kg per minute for 5 days, and this caused a significant decrease in renal plasma flow but no change in glomerular filtration rate. Infusion of Ang II into L-NAME-pretreated dogs for an additional 5 days further decreased renal plasma flow and glomerular filtration 14% and 11%, respectively. However, the effects of Ang II and L-NAME on renal plasma flow were only additive on days 3 and 5 of this period, and the effects on glomerular filtration were additive on day 3 but were potentiated on day 5.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Jun
PMID:Role of nitric oxide in long-term angiotensin II-induced renal vasoconstriction. 850 5

The role of renal interstitial pressure was examined in mediating the sodium retention induced by blockade of nitric oxide synthesis. The effects of intravenous NG-nitro-L-arginine-methyl ester (L-NAME), a synthesis inhibitor, on renal hemodynamics, renal interstitial hydrostatic pressure, and sodium and lithium excretion were determined. L-NAME (50 micrograms/kg per minute) was infused for 75 minutes in Sprague-Dawley rats (n = 7) in which renal perfusion pressure was permitted to rise in parallel with systemic arterial pressure and in rats (n = 8) in which renal perfusion pressure was serocontrolled constant at basal levels. Infusion of L-NAME raised renal perfusion pressure from 122 +/- 6 to 157 +/- 4 mm Hg in the nonservocontrolled group but not in the servocontrolled group (118 +/- 3 mm Hg). L-NAME decreased renal plasma flow and glomerular filtration rate to the same level in both rat groups. L-NAME significantly decreased sodium excretion (1.38 +/- 0.41 to 0.36 +/- 0.14 microEq/min and 1.19 +/- 0.46 to 0.30 +/- 0.05 microEq/min, respectively), fractional excretion of lithium (25.7 +/- 1.7% to 16.7 +/- 2.3% and 25.6 +/- 4.0% to 18.2 +/- 1.7%), and renal interstitial hydrostatic pressure (6.4 +/- 1.4 to 3.2 +/- 0.9 mm Hg and 6.3 +/- 1.8 to 2.7 +/- 0.9 mm Hg) in servocontrolled and nonservocontrolled groups. However, there was no significant difference in the renal hemodynamic and excretory responses to L-NAME between the servocontrolled and nonservocontrolled groups. In summary, reductions in sodium excretion during inhibition of nitric oxide synthesis are associated with significant reductions in renal interstitial hydrostatic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Jun
PMID:Role of renal interstitial pressure as a mediator of sodium retention during systemic blockade of nitric oxide. 850 6

Although an increased prevalence of hypertension is associated with insulin-dependent diabetes, little is known about the effect of streptozotocin (STZ) diabetes on arterial pressure (AP) regulation in rats. Changes in AP induced by STZ, as well as associated factors in blood pressure regulation such as baroreflex sensitivity, plasma renin activity (PRA), plasma glucose and insulin levels and endothelium participation, were studied in male Wistar rats weighing 287 +/- 10 g. The same seven conscious rats were used for all measurements before and after STZ diabetes. AP pulses were stored on a videotape recorder and processed by a data acquisition system. Baroreflex sensitivity was evaluated by measuring heart rate (HR) changes induced by AP variations produced by phenylephrine and sodium nitroprusside injection. The effect of inhibition of nitric oxide synthesis with NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg i.v. bolus plus infusion at 20 mg kg-1 h-1) on AP was evaluated in another set of rats (6 normal and 5 submitted to STZ treatment). STZ induced hyperglycemia (306 +/- 19 mg/dl), a reduction in mean arterial pressure (MAP, from 116 +/- 5 to 101 +/- 4 mmHg) and no changes in HR (320 +/- 10 vs 298 +/- 14 bpm). The tachycardic response to arterial pressure decreases was impaired (-2.29 +/- 0.5 vs -4.5 +/- 0.7 bpm/mmHg, in control) while the bradycardic response to arterial pressure increases was unchanged. Pressure responsiveness to phenylephrine was impaired after STZ (3.78 +/- 0.4 vs 6.73 +/- 0.8 mmHg microU-1 ml-1, in control).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Streptozotocin diabetes modifies arterial pressure and baroreflex sensitivity in rats. 852 May 49

1. Angiotensin converting enzyme (ACE) inhibition has been shown to restore the impaired endothelial function in hypertension, but the mediators underlying the promoted endothelium-dependent dilatation have not been fully characterized. Therefore, we investigated the effects of 10-week-long quinapril therapy (10 mg kg-1 day-1) on responses of mesenteric arterial rings in vitro from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 2. Endothelium-dependent relaxations of noradrenaline (NA)-precontracted rings to acetylcholine (ACh) and adenosine 5'-diphosphate (ADP) were similar in WKY rats and quinapril-treated SHR and more pronounced than in untreated SHR. The nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) attenuated the relaxations in both WKY groups and quinapril-treated SHR, and completely inhibited them in untreated SHR. When endothelium-dependent hyperpolarization was prevented by precontraction of the preparations with potassium chloride (KCl), no differences were found in relaxations to ACh and ADP between the study groups. In addition, in NA-precontracted rings the L-NAME- and indomethacin-resistant relaxations to ACh were partially prevented by apamin, an inhibitor of calcium-activated potassium channels. 3. Interestingly, in quinapril-treated SHR but not in the other groups, exogenous bradykinin potentiated the relaxations to ACh in both NA- and KCl-precontracted arterial rings. 4. Contractile sensitivity of endothelium-intact rings to NA was reduced in SHR by quinapril, and was more effectively increased by L-NAME in quinapril-treated than untreated SHR. 5. In conclusion, since the relaxations to ACh and ADP in quinapril-treated SHR were augmented in the absence and presence of NO synthesis inhibition but not under conditions which prevented hyperpolarization, enhanced endothelium-dependent relaxation after long-term ACE inhibition can be attributed to increased endothelium-dependent hyperpolarization. However, the potentiation of the response to ACh by exogenous bradykinin in quinapril-treated SHR, as well as the increased attenuating effect of the endothelium on NA-induced contractions in these animals appear to result from enhanced endothelium-derived NO release.
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PMID:Endothelial function in spontaneously hypertensive rats: influence of quinapril treatment. 854 88

The effect of chronic inhibition of nitric oxide (NO) biosynthesis has been investigated in two models of acute inflammation induced by carrageenin, i.e., paw oedema and pleurisy. Chronic inhibition of NO biosynthesis was achieved by including N omega-nitro-L-arginine methyl ester (L-NAME) in the drinking water to give a dose of approximately 75 mumol/rat/day for 2 and 4 weeks. Control animals received either tap water alone or the inactive enantiomer D-NAME. Since chronic NO inhibition increases blood pressure, rats made hypertensive (2 kidney-1 clip model; 2K-1C) were used to evaluate the effect of hypertension on the carrageenin-induced paw oedema. In a separate set of experiments, L-NAME-treated animals concomitantly received captopril (140 mumol/rat/day) to prevent hypertension. Animals chronically treated with L-NAME (but not D-NAME) for 2 and 4 weeks developed hypertension to the same extent as 2K-1C rats. Carrageenin-induced paw oedema was significantly reduced in animals chronically treated with L-NAME, but not with D-NAME or in 2K-1C rats. Subplantar injection of iloprost completely reversed the inhibition of paw oedema caused by L-NAME. Captopril (140 mumol/rat/day) significantly lowered the high blood pressure levels induced by L-NAME but did not significantly affect the inhibition of paw oedema caused by L-NAME. No changes in vascular permeability, as assessed by Evans blue extravasation, were observed in L-NAME-treated animals. The chronic treatment with L-NAME for 2 and 4 weeks did not inhibit carrageenin-induced leucocyte migration and fluid exudation into the pleural cavity. Although carrageenin-induced paw oedema is reduced in L-NAME-treated rats, this response reflects a decrease in local blood flow rather than an effect on vascular permeability.
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PMID:Effect of chronic nitric oxide synthesis inhibition on the inflammatory responses induced by carrageenin in rats. 856 27

Chronic nitric oxide inhibition exacerbates hypertension and nephrosclerosis in spontaneously hypertensive rats (SHRs). In this study, we determined whether angiotensin-converting enzyme (ACE) inhibition could prevent or reverse the systemic, renal, and glomerular hemodynamic alterations and the pathological changes of nephrosclerosis. Four groups of 20-week-old SHRs were studied: group 1, untreated controls; group 2, treated with N omega-nitro-L-arginine methyl ester (L-NAME, 50 mg/L for 3 weeks); group 3, L-NAME cotreated with quinapril (3 mg.kg-1.d-1 for 3 weeks); and group 4, L-NAME for 3 weeks followed by quinapril for 3 weeks (same doses). The results of this study demonstrated that both cotreatment (group 3) and posttreatment (group 4) with quinapril reduced mean arterial pressure (186 +/- 9 and 192 +/- 9 mm Hg, respectively, compared with group 2 SHRs, 221 +/- 5 mm Hg) and total peripheral resistance index associated with significant reductions in afferent and efferent arteriolar resistances; nephrosclerosis pathological scores; and urinary protein excretion (all at least P < .01). ACE inhibition also significantly increased stroke index, single-nephron glomerular filtration rate, and ultrafiltration coefficient compared with the L-NAME SHRs. Most notable were the findings that cotreatment with quinapril completely prevented the renal glomerular hemodynamic alterations with reduced glomerular capillary hydrostatic pressure and efferent arteriolar resistance compared with both the untreated and the L-NAME-treated SHRs (all at least P < .01). Posttreatment with quinapril also reversed the glomerular injury (subcapsular, -83%; juxtamedullary, -56%) and arteriolar (-87%) injury scores obtained from renal biopsy specimens (P < .005 and P < .0001, respectively). These changes were associated with decreased periarteriolar fibronectin and increased afferent arteriolar alpha-smooth muscle actin deposition (immunohistochemistry). These data, therefore, demonstrate that ACE inhibition not only prevents but also reverses L-NAME-exacerbated severe nephrosclerosis in SHRs, as indicated by improved systemic, renal, and glomerular hemodynamic changes, proteinuria, and histological alterations.
Hypertension 1996 Feb
PMID:ACE inhibition prevents and reverses L-NAME-exacerbated nephrosclerosis in spontaneously hypertensive rats. 856 38

The aim of this study was to establish that inhibiting nitric oxide (NO) production with NG-nitro-L-arginine methyl ester (L-NAME) results in high blood pressure conditions in chronically treated pregnant rats. To validate the model, the effects of L-arginine (the substrate for NO) and D-arginine (the stereoisomer of L-arginine which is not a substrate for NO synthesis) were studied on blood pressure and fetal weights. The effects of a progesterone agonist, promegestone (R5020) and 17 beta-oestradiol were also explored. The NO synthase inhibitor L-NAME was chronically infused s.c. into pregnant rats from day 17 of gestation, either alone or with the simultaneous infusion of L-arginine and injections of sex steroid hormones (promegestone and oestradiol), compounds that may act in the pathogenic pathways of pre-eclampsia. Systolic blood pressure was measured daily. Weight and mortality of pups were recorded immediately after delivery. Blood pressure was elevated significantly in rats treated with L-NAME for only 1 day following infusion; there was a consistent decline during the next 3 days of pregnancy followed by a dramatic and significant rise just prior to delivery and post-partum. Fetal weights were reduced significantly in the L-NAME-treated rats. Co-treatment of L-NAME-infused rats with L-arginine reversed both the increase in blood pressure and the decrease in fetal weights observed with L-NAME alone. R5020, but not oestradiol, also reduced blood pressure and increased fetal weights in the L-NAME-treated animals. NO appears to play essential roles in the regulation of blood pressure during pregnancy, as well as in fetal perfusion and fetal weights at delivery. This study also indicates that progesterone, and not oestrogen, may regulate the vascular adaptations during normal pregnancy. L-Arginine and progesterone agonists like promegestone may have beneficial effects on the high blood pressure levels and reduced fetal weights associated with pre-eclampsia.
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PMID:Pre-eclampsia-like conditions produced by nitric oxide inhibition: effects of L-arginine, D-arginine and steroid hormones. 856

The present study was designed to investigate the role of cardiopulmonary reflex, more specifically the Bezold-Jarisch reflex, in experimental hypertension induced by chronic administration of Nw-nitro-L-arginine methyl ester (L-NAME) (0.5 mg/ml) added to the drinking water for 6 days. The study was performed in male Wistar rats (200-350 g), 9 animals per group. L-NAME ingestion caused a significant increase in resting mean arterial pressure (MAP: 182 +/- 4 mmHg) and heart rate (HR: 447 +/- 20 bpm) when compared to untreated rats (MAP: 112 +/- 3 mmHg and HR: 355 +/- 10 bpm). Cardiopulmonary receptors were chemically stimulated with bolus injections of 5-hydroxytryptamine (5-HT, 4-10 micrograms/kg, iv) followed by measuring the falls in diastolic arterial pressure (DAP) and HR in conscious and freely moving animals. As expected, the responses to intravenous injections of 5-HT consisted of a dose-dependent reduction in HR (from 26 +/- 14 to 175 +/- 25 bpm) and DAP (from 7 +/- 4 to 39 +/- 3 mmHg) in the control rats. Both bradycardia and diastolic hypotension were significantly accentuated in the L-NAME animals (approximately 30%). These data suggest that, in contrast to other models of hypertension, in the present one caused by inhibition of nitric oxide synthesis, the Bezold-Jarisch reflex is exaggerated. This neural dysfunction could be related to changes in the cardiac vagal efferent or effector.
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PMID:Exaggerated Bezold-Jarisch reflex in the hypertension induced by inhibition of nitric oxide synthesis. 858 Aug 77

Chronic nitric oxide (NO) blockade promotes progressive hypertension, marked renal vasoconstriction, and glomerular and renal interstitial injury. Inhibition of the renin/angiotensin system prevents only partially the functional and structural abnormalities associated with this model. Because endothelin (ET) is a powerful endogenous vasoconstrictor and promitogen, we examined the hypothesis that it might also mediate the hemodynamic and renal structural effects of chronic NO blockade. Four groups of 16 adult male Munich-Wistar rats were studied. Group C received daily i.p. saline injections and no drug treatment. Group C+FR received daily i.p. injections of the ETA inhibitor FR139317, 32 mg/kg. Group NAME received the NO inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), 65 mg/kg/day in the drinking water, and group NAME+FR received both L-NAME and FR139317. At 2 weeks of treatment, renal and systemic hemodynamic parameters assessed under anesthesia were similar in Groups C and C+FR. Rats of Group NAME exhibited systemic hypertension and renal vasoconstriction characteristic of this model. FR139317 was ineffective in preventing these abnormalities in Group NAME+FR. In eight additional rats of each group observed at 30 days, FR139317 treatment was equally inactive in the prevention of glomerular collapse and interstitial expansion, the two chief modalities of renal injury in this model. These results suggest that ET does not participate, at least via the ETA receptor, in the pathogenesis of hypertension, renal dysfunction, or renal injury associated with the chronic NO inhibition model.
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PMID:Do ETA receptors participate in the hemodynamic and renal effects of chronic nitric oxide blockade? 858 46

1. Acute treatment with the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) produces cerebral oligaemia. The effects of repeated exposure to L-NAME upon cerebral blood flow were examined to determine whether the enhanced NOS inhibition reported following chronic treatment might reduce cerebral perfusion to ischaemic levels. 2. Rats were treated with L-NAME (75 mg kg-1, i.p.) once daily for 10 days. Local cerebral blood flow and glucose utilization were measured by [14C]-iodoantipyrine and [14C]-2-deoxyglucose quantitative autoradiography respectively, either 1 h or 15 h after the last injection. A second group of rats was injected (i.p.) only once with L-NAME, either 1 h or 15 h prior to the measurement procedures. 3. Mean arterial blood pressure (MABP) was significantly increased (+35%) 1 h after a single injection of L-NAME. Although the hypertension was reduced 15 h after the injection (+13%), MABP remained significantly higher than control. 4. Local cerebral blood flow was significantly decreased 1 h after a single injection of L-NAME (ranging from -45% to -54%), and remained so even after 15 h (-39% to -48%). At neither time-point was there any change in glucose utilization. 5. At 15 h after the final injection of the chronic L-NAME treatment protocol, MABP was significantly elevated from control (+58%) and was also significantly higher than at 1 h following a single injection (+20%). There was no effect upon the established hypertension when rats treated chronically with L-NAME were challenged with a further injection of the drug and MABP was measured 1 h later, suggesting saturation of NOS inhibition. 6. Although reduced, cerebral blood flow was not significantly different from control when measured 15 h after the last injection of the chronic L-NAME treatment. When rats treated chronically with L-NAME were subjected to a further challenge with the drug, cerebral blood flow was reduced when measured 1 h after the acute injection (ranging from -34% to -41%). There was however evidence of some attenuation in the response when compared to that measured 1 h after a single injection of L-NAME (ranging from -45% to -54%). Thus, the cerebral circulation shows no evidence of either sustained L-NAME-induced vasoconstriction or saturated NOS inhibition following 10 daily injections of L-NAME. Chronic L-NAME treatment had no effect upon cerebral glucose use. 7. The trend towards re-establishment of cerebrovascular dilator tone and the normalization of cerebral flow-metabolism relationships could explain the lack of any ischaemic damage found in chronically treated rats, but the loss of an extended autoregulatory range afforded by acute L-NAME treatment may be responsible for an increased incidence of stroke.
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PMID:Cerebrovascular consequences of repeated exposure to NG-nitro-L-arginine methyl ester. 859 Oct 3


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