The objective of this study was to determine in conscious dogs the role of endothelium-derived nitric oxide in mediating the arterial pressure and renal response to a prolonged increment of sodium intake. After a control period of 3 days, an inhibitor of nitric oxide synthesis, NG-nitro-L-arginine-methyl ester, was infused intravenously during 5 consecutive days (0.1 micrograms/kg per minute). Sodium intake (80 mmol/d) did not change throughout the experiment in one group (n = 4). In another group (n = 6), 1 day after infusion of this inhibitor was started, sodium intake increased from 80 to 300 mmol/d during 4 consecutive days. Inhibition of nitric oxide synthesis in dogs with normal sodium intake induced a significant decrease in natriuresis and diuresis (P < .05) without changes in arterial pressure. However, in dogs treated with the nitric oxide synthesis inhibitor, mean arterial pressure increased from 95.2 +/- 3.3 to 106.2 +/- 4.0 mm Hg (P < .01) the first day that sodium intake was elevated and remained increased the following 3 days. In a different group of dogs (n = 5), the increment of sodium intake during 4 days did not induce changes in arterial pressure when nitric oxide synthesis was not inhibited. Cumulative sodium balance was higher (P < .01) in dogs treated simultaneously with the nitric oxide synthesis inhibitor and high sodium intake (158 +/- 21 mmol sodium) than in those treated only with the nitric oxide synthesis inhibitor (82 +/- 19 mmol sodium) or with high sodium intake (36 +/- 13 mmol sodium).(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic blockade of nitric oxide (NO) synthesis results in marked increases in the renal vascular resistance (RVR) and decreases in the glomerular filtration rate (GFR) and renal plasma flow (RPF). The renal hemodynamic effect of systemic NO blockade is most likely due to an integration of direct and indirect renal actions. The quantitative importance of local intrarenal blockade of NO synthesis on renal hemodynamics has not been fully elucidated. Therefore, the purpose of this study was to compare the renal hemodynamic effects of intrarenal vs. systemic NO synthesis blockade on renal hemodynamics. Nitro-L-arginine methyl ester (L-NAME) was infused intrarenally at a rate of 3 micrograms/kg/min for 180 min in conscious chronically instrumented dogs (n = 7). Intrarenal infusion of L-NAME for 180 min resulted in a 12% decrease in RPF, 14% increase in RVR, and no effect on mean arterial pressure (MAP) or GFR. In contrast, infusion of L-NAME intravenously at a rate of 10 micrograms/kg/min for 180 min increased the RVR by 124% and decreased the RPF by 55% and GFR by 45%. The MAP and heart rate both increased in response to intravenous administration of L-NAME. The results of this study suggest that the renal hemodynamic effects of systemic administration of L-NAME may, in large part, be secondary to extrarenal effects of NO synthesis blockade, possibly via activation of the sympathetic nervous system.

The objective of the present study was to determine the role of endothelium-derived nitric oxide in mediating the renal response to extracellular volume expansion with isotonic saline (5% body weight). In anesthetized dogs (n = 7) and before volume expansion, nitric oxide synthesis was inhibited in the right kidney by continuous intrarenal infusion of NG-nitro-L-arginine-methyl ester (1 microgram/kg/min). Arterial pressure and renal hemodynamics of both kidneys did not change significantly either during nitric oxide synthesis inhibition or during 5% volume expansion. However, in response to extracellular volume expansion, increases in natriuresis, diuresis, and fractional excretion of lithium (an index of proximal sodium reabsorption) were inhibited in the right kidney by 27%, 28%, and 41%, respectively, when compared with the contralateral kidney. Increases of renal interstitial hydrostatic pressure during 5% volume expansion were not statistically different between both kidneys. In another group of dogs (n = 4), the administration of L-arginine (0.5 mg/kg/min) into the right renal artery prevented the renal effects induced by the nitric oxide synthesis inhibitor during volume expansion. The findings in this study suggest that nitric oxide production plays an important role in regulating the renal response to extracellular volume expansion. The proximal tubule seems to be involved in the reduced renal excretory response to volume expansion during nitric oxide synthesis inhibition.

Metabolic syndrome (MetS) has become one of the main concerns for public health because of its link to cardiovascular disease. Murine models have been used to study the effect of MetS on the cardiovascular system, but they have limitations for studying cardiac electrophysiology. In contrast, the rabbit cardiac electrophysiology is similar to human, but a detailed characterization of the different components of MetS in this animal is still needed. Our objective was to develop and characterize a diet-induced experimental model of MetS that allows the study of cardiovascular remodeling and arrhythmogenesis. Male NZW rabbits were assigned to control (n = 15) or MetS group (n = 16), fed during 28 weeks with high-fat, high-sucrose diet. We measured weight, morphological characteristics, blood pressure, glycaemia, standard plasma biochemistry and the metabolomic profile at weeks 14 and 28. Liver histological changes were evaluated using hematoxylin-eosin staining. A mixed model ANOVA or unpaired t-test were used for statistical analysis (P<0.05). Weight, abdominal contour, body mass index, systolic, diastolic and mean arterial pressure increased in the MetS group at weeks 14 and 28. Glucose, triglycerides, LDL, GOT-AST, GOT/GPT, bilirubin and bile acid increased, whereas HDL decreased in the MetS group at weeks 14 and 28. We found a 40% increase in hepatocyte area and lipid vacuoles infiltration in the liver from MetS rabbits. Metabolomic analysis revealed differences in metabolites related to fatty acids, energetic metabolism and microbiota, compounds linked with cardiovascular disease. Administration of high-fat and high-sucrose diet during 28 weeks induced obesity, glucose intolerance, hypertension, non-alcoholic hepatic steatosis and metabolic alterations, thus reproducing the main clinical manifestations of the metabolic syndrome in humans. This experimental model should provide a valuable tool for studies into the mechanisms of cardiovascular problems related to MetS, with special relevance in the study of cardiovascular remodeling, arrhythmias and SCD.

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)