nitroarginine and Proteinuria

Experiments on Wistar rats showed that single intraperitoneal injection nonselective NO-synthase inhibitor L-NAME in a dose of 50 mg/kg was followed by transient proteinuria and albuminuria. This effect was not reproduced by injection of ODQ, an inhibitor of intracellular effects of NO, and arginine, but D-NAME, an optical isomer of L-NAME not blocking NO-synthase, produced similar, though less pronounced effect. The degree of proteinuria and albuminuria increased in combined treatment with nitroarginine methyl esters and 1-deamino-arginine vasotocin or arginine vasopressin. Proteinuria during treatment with arginine derivatives attests to not only their effect on the charge of the filtration membrane, but also the participation of NO-dependent processes in the regulation of ultrafiltration in renal glomeruli.

Topics: Albumins; Albuminuria; Animals; Arginine Vasopressin; Enzyme Inhibitors; Female; Kidney; Kidney Glomerulus; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Proteinuria; Rats; Rats, Wistar; Vasotocin

Left ventricular systolic dysfunction (LVSD) in patients with chronic kidney disease (CKD) is associated with poorer prognosis. Because patients with CKD often exhibit progressively decreased nitric oxide (NO) availability and inhibition of NO production can reduce cardiac output, we hypothesized that loss of NO availability in CKD contributes to pathogenesis of LVSD. Subtotally nephrectomized (SNX) rats were treated with a low dose of the NO synthase inhibitor N(omega)-nitro-L-arginine (L-NNA; 20 mg/l water; SNX+L-NNA) and compared with relevant control groups. To study permanent changes separate from hemodynamic effects, L-NNA was stopped after week 8 and rats were followed up to week 15, until blood pressure was similar in SNX+L-NNA and SNX groups. To study effects of NO depletion alone, a control group with high-dose L-NNA (L-NNA-High: 100 mg/l) was included. Mild systolic dysfunction developed at week 13 after SNX. In SNX+L-NNA, systolic function decreased by almost 50% already from week 4 onward, together with markedly reduced whole body NO production and high mortality. In L-NNA-High, LVSD was not as severe as in SNX+L-NNA, and renal function was not affected. Both LVSD and NO depletion were reversible in L-NNA-High after L-NNA was stopped, but both were persistently low in SNX+L-NNA. Proteinuria increased compared with rats with SNX, and glomerulosclerosis and cardiac fibrosis were worsened. We conclude that SNX+L-NNA induced accelerated and permanent LVSD that was functionally and structurally different from CKD or NO depletion alone. Availability of NO appears to play a pivotal role in maintaining cardiac function in CKD.

Topics: Animals; Blood Pressure; Body Weight; Echocardiography; Enzyme Inhibitors; Hematocrit; Hypertension, Renal; Male; Nephrectomy; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Poult Enteritis Mortality Syndrome; Proteinuria; Rats; Rats, Inbred Lew; Renal Insufficiency, Chronic; Systole; Urine; Ventricular Dysfunction, Left

Hypertension demands cardiac synthetic and metabolic adaptations to increased afterload. We studied gene expression in two models of mild hypertension without overt left ventricular hypertrophy using the NO synthase inhibitor nitro-L-arginine (L-NNA) and the glutathione depletor buthionine-S,R-sulfoximine (BSO). Mice were administered L-NNA, BSO, or water for 8 weeks. RNA of left ventricles was pooled per group, reverse transcribed, Cy3 and Cy5 labeled, and hybridized to cDNA microarrays. Normalized log(2) Cy3/Cy5 ratios of > or =0.7 or < or =-0.7 were considered significant. L-NNA and BSO both caused hypertension. Gene expression was regulated in cytoskeletal components in both models, protein synthesis in L-NNA-treated mice, and energy metabolism in BSO-treated mice. Energy metabolism genes shared several common transcription factor-binding sites such as Coup-Tf2, of which gene expression was increased in BSO-treated mice, and COMP-1. Characterization of the left ventricular adaptations as assessed with gene expression profiles reveals differential expression in energy and protein metabolism related to the pathogenetic background of the hypertension.

Topics: Animals; Binding Sites; Blood Pressure; Body Weight; Buthionine Sulfoximine; Cluster Analysis; Energy Metabolism; Enzyme Inhibitors; Female; Gene Expression; Gene Expression Profiling; Glutamate-Cysteine Ligase; Glutathione; Glycolysis; Heart; Heart Ventricles; Hypertension; Hypertrophy, Left Ventricular; Mice; Mice, Inbred C57BL; Myocardium; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Oligonucleotide Array Sequence Analysis; Organ Size; Protein Biosynthesis; Proteinuria; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors

Our previous studies in rodent models of nephropathy demonstrate that 2-hydroxyestradiol (2HE), an estradiol metabolite with little estrogenic activity, exerts renoprotective effects. In vivo, 2HE is readily converted to 2-methoxyestradiol (2ME), a major estradiol metabolite with no estrogenic activity. The goal of this study was to determine whether 2ME has renal and cardiovascular protective effects in vivo. First, the acute (90 minutes) and chronic (14 days) effects of 2ME (10 microg/kg/h) on blood pressure and renal function were examined in normotensive and spontaneously hypertensive rats (SHR). Second, a rat model of cardiovascular and renal injury induced by chronic nitric oxide synthase inhibition (N-nitro-L-arginine; 40 mg/kg/d; LNNA group) was used to examine the protective effects of estradiol metabolites. Subsets of LNNA-treated rats were administered either 2HE or 2ME (10 microg/kg/h via osmotic minipump; LNNA+2ME and LNNA+2HE groups, respectively. 2-Methoxyestradiol had no acute or chronic effects on blood pressure or renal function in normotensive animals or on hypertension in SHR. Prolonged, 5-week NOS inhibition induced severe cardiovascular and renal disease and high mortality (75%, LNNA group). 2ME, but not 2HE, significantly decreased elevated blood pressure and attenuated the reduction in GFR. 2HE delayed the onset of proteinuria, whereas no proteinuria was detected in the 2-ME group. 2HE and 2ME reduced mortality rate by 66% and 83%, respectively (P < 0.001). In the kidney, 2HE and 2ME abolished LNNA-induced interstitial and glomerular inflammation, attenuated glomerular collagen IV synthesis, and inhibited glomerular and tubular cell proliferation. In the heart, 2HE and 2ME markedly reduced vascular and interstitial inflammation and reduced collagen synthesis and vascular/interstitial cell proliferation. This study provides the first evidence that, in a model of severe cardiovascular and renal injury, 2-methoxyestradiol (a major nonestrogenic estradiol metabolite) exerts renal and cardiovascular protective effects and reduces mortality.

Topics: 2-Methoxyestradiol; Animals; Antigen-Presenting Cells; Body Weight; Cardiovascular Diseases; Creatinine; Enzyme Inhibitors; Estradiol; Glomerular Filtration Rate; Heart; Infusions, Intravenous; Kidney Diseases; Male; Nitric Oxide Synthase; Nitroarginine; Proteinuria; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Renal Circulation; Time Factors

Chronic nitric oxide (NO) synthase (NOS) inhibition results in renal injury. Hypertension is an important risk factor for renal injury. We studied the influence of preexistent hypertension on the sensitivity for renal injury induced by chronic NOS inhibition in rats. Spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were treated with 3, 10, 30 and 100 mg/l Nomega-nitro-L-arginine (L-NNA) until death. Systolic blood pressure and proteinuria were measured regularly and compared with time-control measurements in untreated SHR and WKY. In WKY, 3 and 10 mg/l L-NNA did not affect systolic blood pressure, while 30 and 100 mg/l L-NNA resulted in an increase in systolic blood pressure after 12 and 4 weeks, respectively. In contrast in SHR, every dose of L-NNA resulted in an increase in systolic blood pressure after 2 weeks. In WKY, 3 and 10 mg/l L-NNA did not affect proteinuria or survival, while 30 and 100 mg/l L-NNA resulted in an increase in proteinuria after 30 and 9 weeks, and a median survival of 36 and 12 weeks, respectively. In SHR, 3, 10, 30 and 100 mg/l L-NNA resulted in an increase in proteinuria after 30, 12, 3 and 3 weeks, and a median survival of 41, 20, 5 and 3 weeks, respectively. Thus, at every dose of the inhibitor, chronic NOS inhibition resulted in far earlier increases in systolic blood pressure and proteinuria and a marked increase in mortality in SHR as compared to WKY. Indeed, a very low dosage of L-NNA that caused no harm in WKY was followed by marked increases in proteinuria and blood pressure and decreased survival in SHR. Hypertension strongly increases the vulnerability to cardiovascular risk factors that compromise the NO-system.

Topics: Animals; Blood Pressure; Dose-Response Relationship, Drug; Enzyme Inhibitors; Genetic Predisposition to Disease; Hypertension; Kidney; Male; Nitric Oxide Synthase; Nitroarginine; Proteinuria; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Survival Analysis; Systole; Time Factors

To elucidate the role of nitric oxide (NO) and renin-angiotensin system (RAS) in the development of salt-sensitive hypertension, we investigated the pressor responses and renal histologic changes after long-term inhibition of endogenous NO synthesis in Dahl-Iwai salt-sensitive (DS) and salt-resistant (DR) rats under salt-re-stricted conditions that exaggerate RAS activation. Male DS and DR rats (6 weeks old) were fed with a low-salt (0.3%) diet for 5 weeks. NG-nitro-L-arginine (L-NA; dissolved in 60 mg/L deionized water), an arginine analogue acting as a NO-inhibitor, was also administered for 5 weeks. L-NA administration induced a gradual increase in systolic blood pressure (SBP) in both strains, and the pressor response in DS rats was apparently more enhanced relative to that in DR rats. Urinary nitrate plus nitrite (u-NOx) excretion was decreased by L-NA, with a significant negative correlation between SBP and u-NOx excretion in DS rats but not in DR rats. Plasma renin activity and urinary aldosterone level were significantly increased in L-NA-treated DS rats on week 5. Marked histologic changes with glomerular sclerosis and increased proteinuria and urinary N-acetyl-beta-glucosaminidase excretion were found in L-NA-treated DS rats but not DR rats. Competitive RT-PCR of mRNA extracted from the glomeruli revealed that angiotensin II type 1 receptor (AT1R) mRNA level was significantly lower in DS rats than in DR rats at week 2, and that L-NA administration significantly reduced glomerular AT1R level of DS rats at week 5, possibly because of downregulation. Our results showed that, even under sodium restriction, the pressor response and renal injury induced by chronic NO inhibition were markedly more enhanced in DS rats than in DR rats, which indicates that depletion of NO participates in both the development of hypertension and glomerular injury in DS rats through a potential activation of RAS irrespective of sodium loading. These data suggest that endogenous NO is an essential determinant of salt-sensitive hypertension in DS rats.

Topics: Aldosterone; Animals; Blood Pressure; Diet, Sodium-Restricted; Down-Regulation; Glucuronidase; Hypertension; Kidney Glomerulus; Male; Nitrates; Nitric Oxide; Nitrites; Nitroarginine; Proteinuria; Rats; Rats, Inbred Dahl; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin; Renin; Renin-Angiotensin System; RNA, Messenger; Sclerosis

Chronic nitric oxide (NO) synthase inhibition in rats causes hypertension, renal vascular injury, and proteinuria. NO deficiency increases superoxide (O(2)(-)) activity, but the effects of antioxidant treatment on renal injury have not been studied in this model. Exposure of rats to N omega-nitro-L-arginine (L-NNA) for 4 d markedly decreased NO-dependent relaxation in aortic rings and increased glomerular and renal interstitial monocyte influx, but renal O(2)(-) activity was not increased. After 7 d, BP and proteinuria were significantly increased. After 21 d of L-NNA treatment, rats displayed severe hypertension, decreased GFR, marked proteinuria, glomerular ischemia, renal vascular and tubulointerstitial injury, and complete loss of NO-dependent relaxation. Renal O(2)(-) activity was markedly increased [lucigenin-enhanced chemiluminescence (LEC), 279 +/- 71 versus 50 +/- 7 counts/10 mg, P < 0.01; electron paramagnetic resonance spectroscopy, 0.57 +/- 0.05 versus 0.34 +/- 0.04 U/10 mg, P < 0.05]. Apocynin, a specific inhibitor of NADPH oxidase, and diphenyleneiodonium, an inhibitor of flavin-containing enzymes, completely inhibited LEC signals in vitro, whereas allopurinol had no effect, indicating that NAD(P)H oxidase plays a major role in superoxide production in the kidney. Endothelial function remained impaired during cotreatment with alpha-tocopherol and there was no effect on hypertension or tubulointerstitial injury, but glomerular ischemia, decreases in GFR, and renal vascular injury were prevented and proteinuria was ameliorated. Renal LEC signals were intermediate between control and L-NNA-alone values (181 +/- 84 counts/10 mg). Chronic NO synthase inhibition in rats results in marked increases in renal cortical O(2)(-) activity, mediated by flavin-dependent oxidases. The absence of early increases in renal O(2)(-) activity, in the presence of endothelial dysfunction and macrophage influx, indicates that increased renal O(2)(-) activity is neither attributable to NO deficiency per se nor solely related to macrophage influx. The improvement of glomerular function and amelioration of renal vasculitis and proteinuria with vitamin E cotreatment indicate that oxidants are involved in the pathogenesis of renal injury in this model. However, markedly impaired endothelial function and unabated hypertension persist with vitamin E treatment and seem to be directly attributable to NO deficiency.

Topics: Animals; Antioxidants; Aorta; Blood Pressure; Enzyme Inhibitors; Hypertension; Ischemia; Kidney; Kidney Cortex; Kidney Glomerulus; Macrophages; Male; Monocytes; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Proteinuria; Rats; Rats, Sprague-Dawley; Superoxides; Systole; Time Factors; Vasodilation; Vitamin E

Burn injuries trigger a pronounced inflammatory response in the burned skin, resulting in oedema formation and impaired circulation. This response involves activation of the nitric oxide (NO) synthetic pathway, which could play a key role in the complex hemodynamic and hemostatic changes occurring as a result of a burn trauma. The results presented in full-thickness skin burns of rats show that the NO-precursor, L-arginine (n = 10), inhibit burn-induced plasma extravasation as compared to saline-treated burned controls (n = 10) (p<0.001) to a level not significantly different from nonburned animals. Administration of the NO-synthase inhibitor. NG-nitro-L-arginine (L-NNA) (n = 10), did not significantly influence burn extravasation compared to burned controls. Accumulated urine volume 90 min post-burn increased ten-fold in burned animals treated with L-arginine compared to saline-treated burned controls (p<0.001) and nonburned animals (p<0.001), while L-NNA had no significant effect on diuresis. A significantly increased proteinuria occurred in L-arginine treated burned animals as compared to burned controls and nonburned controls (p<0.001), whereas L-NNA did not significantly influence the leakage of protein in the urine. Activation of NO synthesis significantly suppresses burn edema and strongly increases diuresis along with increased proteinuria.

Topics: Albumins; Animals; Arginine; Burns; Diuresis; Edema; Enzyme Inhibitors; Evans Blue; Male; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Proteinuria; Rats; Rats, Sprague-Dawley; Spectrophotometry; Urine

Men are at greater risk for renal injury than women. We studied whether male rats are more sensitive to the hypertensive and proteinuric effects of chronic nitric oxide synthase (NOS) inhibition than female rats. In addition, we studied whether androgens or estrogens are responsible for differences in sensitivity to proteinuria induced by chronic NOS inhibition. Females and males were treated with 10, 20, 30, and 100 mg/l N(omega)-nitro-L-arginine (L-NNA) during 24 wk. Systolic blood pressure (SBP) and proteinuria were measured regularly and compared with time-control measurements in control females and males. In females and males treatment with 10 mg/l L-NNA had no effect on SBP or proteinuria. Treatment with 20, 30, and 100 mg/l L-NNA resulted in a dose-dependent increase in SBP that was similar in males and females. However, females treated with 20 and 30 mg/l L-NNA were resistant to the development of proteinuria: maximum values were 16 +/- 7 and 46 +/- 21, respectively, vs. 16 +/- 3 mg/day in controls, whereas males treated with those doses showed an increase in proteinuria [139 +/- 35 (P < 0.05) and 318 +/- 82 (P < 0.01), respectively, vs. 55 +/- 11 mg/day in controls]. Treatment with 100 mg/l L-NNA increased proteinuria similarly in both females and males. To study the role of sex hormones in differences in sensitivity to proteinuria induced by mild chronic NOS inhibition, treatment with 20 mg/l L-NNA was repeated in ovariectomized (Ovx) and orchidectomized rats. Ovariectomy did not affect the increase in SBP caused by 20 mg/l L-NNA, but, in contrast to intact females, this dose of L-NNA did cause Ovx rats to develop proteinuria (51 +/- 16 vs. 16 +/- 7 mg/day in control Ovx rats; P < 0.05). Orchidectomy completely prevented the increased SBP as well as proteinuria induced by 20 mg/l L-NNA in male rats. In conclusion, male rats are more sensitive than female rats to develop proteinuria induced by mild chronic NOS inhibition. Estrogens provide some protection in females, whereas androgens are responsible for the increased sensitivity of male rats to proteinuria induced by mild chronic NOS inhibition. Risk factors associated with a compromised nitric oxide system may be more detrimental to the kidney in men than in women.

Topics: Androgens; Animals; Enzyme Inhibitors; Estrogens; Female; Gonadal Steroid Hormones; Male; Nitric Oxide Synthase; Nitroarginine; Orchiectomy; Ovariectomy; Proteinuria; Rats; Rats, Sprague-Dawley; Sex Characteristics

Decreased response to vasopressor agents characterizes pregnancy. Endothelium-derived relaxing factors and vasodilating prostaglandins play an important role in the vascular tone during pregnancy. Since inhibition of nitric oxide (NO) biosynthesis induced by NO2-arginine enriched diet produced hypertension we measured in vivo cardiovascular responses to PGF2 alpha, L-arginine (L-arg) and cicletanine (Cic, IPSEN, France) which enhances PGI2 production. From day 13 to day 20 of gestation 4 groups of female Wistar rats were fed NO2-arg (31 mg/kg/d), NO2-arg+Cic (10 mg/kg/d), Cic enriched or control diet (C). Mean arterial pressure (MAP) was measured via a carotid catheter in anesthetized rats. Injection of PGF2 alpha (50 micrograms/kg) in jugular vein significantly increased MAP in the NO2-arg group versus, NO2-arg+Cic, Cic and C group (+23.5 +/- 3.3 vs +15.7 +/- 2.2, +15.8 +/- 2.2 and +17 +/- 1.85 mmHg; p < 0.01). Injection of L-arg (100 mg/kg) or Cic (1 mg/kg) 5 min before PGF2 alpha produced no modification in MAP in C and Cic group. Likewise in NO2-arg group injection of L-arg or Cic produced a diminished pressor response to PGF2 alpha (+23.5 +/- 3.3 vs -17.5 +/- 1.7 mmHg; p < 0.05 and +15.2 +/- 2.4 mmHg; p < 0.01 respectively). In NO2-arg+Cic group, only injection of Cic induced a diminished pressor response to PGF2 alpha which is more important without L-arg (+15.7 +/- 2.2 vs +9.1 +/- 1.3 mmHg; p < 0.001) or with L-arg (+13.6 +/- 1.5 vs +9.1 +/- 1.3 mmHg; p < 0.01). Cicletanine also significantly diminished the proteinuria in the NO2-arg+Cic group versus NO2-arg group (13.9 +/- 4.36 vs 63.4 +/- 21.6 mmHg; p < 0.01). IN CONCLUSION, chronic NO synthesis inhibition enhanced blood pressure and pressor responses to PGF2 alpha during pregnancy in rats. Chronic administration of cicletanine in Wistar pregnant rats decreases the response to vasopressor agents like PGF2 alpha. Moreover acute and chronic administration of cicletanine blunted the pressor effect, which was lower than in normal gestation.

Topics: Animals; Antihypertensive Agents; Arginine; Blood Pressure; Dinoprost; Enzyme Inhibitors; Female; Hypertension; Nitric Oxide; Nitroarginine; Oxytocics; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy, Animal; Prostaglandins F; Proteinuria; Pyridines; Rats; Rats, Wistar; Vasoconstriction

1. Diabetes mellitus type I was induced in 3-month old male C57 BL/KS-mdb mice (N = 24) by ip injection of streptozotocin (STZ, 45 mg/kg body weight) for 5 days. 2. To determine the possible protective effects of nitric oxide inhibition against hyperglycemia, the STZ-diabetic rats received two doses of NG-nitro-L-arginine- methyl ester (L-NAME) (10 mg/kg body weight and 10 mg/mouse) dissolved in PBS for 45 consecutive days. Another group of STZ-treated rats was similarly treated with L-arginine (5 mg/mouse). 3. Blood glucose levels were 118 +/- 37 mg/dl after 8 days of L-NAME administration (10 mg/kg body weight, N = 12) and 186 +/- 22 mg/dl (N = 12) after 5 days of L-NAME administration at the 5 mg/mouse dose. Treatment with L-arginine (5 mg/mouse, N = 12) caused a significant increase in blood glucose level to 151 +/- 17.5 mg/dl, showing the relevance of nitric oxide formation in this type of diabetes. 4. In STZ-diabetic mice treated with L-NAME (N = 12), diuresis was reduced by approximately 58% compared to STZ animals, whereas in L-arginine-treated animals (N = 12) diuresis returned to STZ levels. Urinary protein excretion, which was significantly affected by STZ (123% compared to control) was significantly reduced by 66% after treatment with L-NAME for 45 days, whereas treatment with L-arginine caused a return to STZ values. 5. Urinary kallikrein excretion, which was reduced by 80% in STZ mice compared to control, returned to control levels after L-NAME treatment. 6. The present results suggest a relationship between nitric oxide levels and the reduction of diabetic state and improved renal function by L-NAME.

Topics: Animals; Arginine; Blood Glucose; Diabetes Mellitus, Experimental; Diuresis; Hyperglycemia; Kallikreins; Male; Mice; Mice, Inbred C57BL; Nitric Oxide; Nitroarginine; Proteinuria; Time Factors

Blockade of the renin-angiotensin system was studied in male Sprague-Dawley rats during long-term inhibition of nitric oxide synthase. Nitro-L-arginine-methyl ester (L-NAME) was placed in the drinking water for 4 weeks (approximately 100 mg/kg per day). Separate groups of rats were coadministered the angiotensin II antagonist A-81988 in the drinking water ranging from approximately 0.001 to 1 mg/kg per day. Control groups received only tap water or A-81988 alone. Each week, rats were placed in metabolic cages, and tail-cuff blood pressures and blood samples were taken. L-NAME produced a sustained elevation in tail-cuff pressure that was completely prevented by A-81988. No changes in creatinine clearance, sodium excretion, plasma creatinine concentration, or blood urea nitrogen were observed. Food and water intakes were identical in all groups. Water excretion was significantly increased in L-NAME-treated animals regardless of additional inhibitor treatment, suggesting a possible role for nitric oxide synthase in the control of water excretion; this effect was independent of blood pressure. Although less potent than A-81988, the angiotensin II antagonist losartan and the angiotensin converting enzyme inhibitor enalapril also blocked L-NAME-induced hypertension. In a separate series of experiments, rats were not given A-81988 until 2 weeks after hypertension had fully developed in L-NAME-treated rats. Within 1 week of treatment with the angiotensin II antagonist, tail-cuff pressure returned to normal. We conclude from these studies that long-term inhibition of endogenous nitric oxide production produces an angiotensin II-dependent form of hypertension.

Topics: Amino Acid Oxidoreductases; Angiotensin II; Animals; Arginine; Diuresis; Dose-Response Relationship, Drug; Hypertension; Male; Nicotinic Acids; Nitric Oxide Synthase; Nitroarginine; Proteinuria; Pyridines; Rats; Rats, Sprague-Dawley; Renin; Tetrazoles; Time Factors

The effect of a calcium antagonist, manidipine, on blood pressure and proteinuria induced by the inhibition of endothelial-derived relaxation factor (EDRF) formation was examined. Manidipine attenuated the increase in blood pressure and prevented proteinuria caused by renal damage associated with the inhibition of EDRF formation in stroke-prone spontaneously hypertensive rat (SHRSP) and Wistar Kyoto (WKY) rats.

Topics: Animals; Arginine; Blood Pressure; Calcium Channel Blockers; Cerebrovascular Disorders; Dihydropyridines; Hypertension; Male; Nitric Oxide; Nitroarginine; Nitrobenzenes; Piperazines; Proteinuria; Rats; Rats, Inbred SHR; Rats, Inbred WKY