Interactive effects of superoxide anion and nitric oxide on blood pressure and renal hemodynamics in transgenic rats with inducible malignant hypertension

2005 ◽  
Vol 289 (4) ◽  
pp. F754-F759 ◽  
Author(s):  
Matthew E. Patterson ◽  
Cynthia R. Mouton ◽  
John J. Mullins ◽  
Kenneth D. Mitchell
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Plasma Flow ◽  
Superoxide Anion ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Renal Hemodynamics ◽  
Malignant Hypertension ◽  
Transgenic Rats

Superoxide anion contributes to the pathogenesis of various forms of hypertension, but its role in the development of malignant hypertension remains unclear. The present study was performed to determine the influence of superoxide anion on blood pressure and renal hemodynamics in transgenic rats with inducible malignant hypertension [strain name: TGR(Cyp1a1Ren2)]. Malignant hypertension was induced in male Cyp1a1-Ren2 rats ( n = 6) through dietary administration of the aryl hydrocarbon, indole-3-carbinol (0.3%) for 7–9 days. Mean arterial pressure (MAP) and renal hemodynamics were measured in pentobarbital sodium-anesthetized Cyp1a1-Ren2 rats before and during intravenous infusion of the superoxide dismutase mimetic tempol (100 μmol/h). Basal MAP and renal vascular resistance (RVR) were elevated in rats induced with indole-3-carbinol compared with noninduced rats ( n = 5) (184 ± 4 vs. 127 ± 3 mmHg, P < 0.01, and 29 ± 2 vs. 21 ± 1 mmHg·ml−1·min·g, P < 0.01, respectively). Hypertensive rats had elevated excretion of urinary 8-isoprostane compared with normotensive rats (41 ± 4 vs. 13 ± 6 pg·min−1·g−1, P < 0.01). There were no differences in renal plasma flow and glomerular filtration rate between groups. Systemic administration of tempol decreased MAP (184 ± 4 to 151 ± 4 mmHg, P < 0.01) and RVR (29 ± 2 to 25 ± 2 mmHg·ml−1·min·g, P < 0.05) in hypertensive but not in normotensive Cyp1a1-Ren2 rats. In addition, tempol administration decreased urinary excretion of 8-isoprostane (41 ± 4 to 25 ± 4 pg·min−1·g−1, P < 0.05). Renal plasma flow and glomerular filtration rate remained unaltered during tempol administration in both groups. The administration of the nitric oxide synthase inhibitor nitro-l-arginine attenuated the decrease in MAP and RVR in response to tempol. These findings indicate that superoxide anion contributes to the elevated RVR and increased arterial blood pressure, by a mechanism that is at least in part nitric oxide dependent, in Cyp1a1-Ren2 rats with malignant hypertension.

scholarly journals Nitric oxide: a potential mediator of amino acid-induced renal hyperemia and hyperfiltration.

1991 ◽  
Vol 1 (12) ◽  
pp. 1271-1277
Author(s):  
A J King ◽  
J L Troy ◽  
S Anderson ◽  
J R Neuringer ◽  
M Gunning ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glomerular Filtration Rate ◽  
Amino Acid ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Competitive Inhibitor ◽  
Arterial Blood

The role of nitric oxide in the modulation of systemic and renal hemodynamics was examined by using N omega-monomethyl-L-arginine (L-NMMA, 110 micrograms/kg/min), a competitive inhibitor of the conversion of L-arginine to nitric oxide. L-NMMA or saline vehicle (9.6 microL/min) was infused intravenously into anesthetized euvolemic Munich-Wistar rats. After 30 min, L-NMMA resulted in a uniform increase in mean arterial blood pressure (111 +/- 1 to 128 +/- 2 mmHg; P less than 0.05) and a modest reduction in renal plasma flow rate (4.4 +/- 0.2 to 4.2 +/- 0.1 mL/min; P less than 0.05), without change in glomerular filtration rate (1.16 +/- 0.03 to 1.15 +/- 0.03 mL/min); vehicle had no effect on these renal parameters. These rats were then subdivided to receive an intravenous infusion (37 microL/min) of either 10% glycine, 11.4% mixed amino acids, or equiosmolar dextrose. L-NMMA pretreatment markedly attenuated glycine-induced hyperfiltration (10 +/- 6 versus 33 +/- 5%, L-NMMA versus vehicle; P less than 0.05) and obliterated the renal hyperemic response (-7 +/- 6 versus 16 +/- 4%, L-NMMA versus vehicle; P less than 0.05). L-NMMA also caused modest blunting of the mixed amino acid-induced hyperfiltration (18 +/- 4 versus 30 +/- 4%, L-NMMA versus vehicle; P = 0.056) but failed to curtail the renal hyperemia (16 +/- 6 versus 20 +/- 4%). Dextrose had no effect on glomerular filtration rate or renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effect of T-type voltage-gated Ca2+ channel disruption on renal plasma flow and glomerular filtration rate in vivo

2014 ◽  
Vol 307 (4) ◽  
pp. F445-F452 ◽  
Author(s):  
Anne D. Thuesen ◽  
Henrik Andersen ◽  
Majken Cardel ◽  
Anja Toft ◽  
Steen Walter ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Voltage Gated

Voltage-gated Ca2+ (Cav) channels play an essential role in the regulation of renal blood flow and glomerular filtration rate (GFR). Because T-type Cav channels are differentially expressed in pre- and postglomerular vessels, it was hypothesized that they impact renal blood flow and GFR differentially. The question was addressed with the use of two T-type Cav knockout (Cav3.1−/− and Cav3.2−/−) mouse strains. Continuous recordings of blood pressure and heart rate, para-aminohippurate clearance (renal plasma flow), and inulin clearance (GFR) were performed in conscious, chronically catheterized, wild-type (WT) and Cav3.1−/− and Cav3.2−/− mice. The contractility of afferent and efferent arterioles was determined in isolated perfused blood vessels. Efferent arterioles from Cav3.2−/− mice constricted significantly more in response to a depolarization compared with WT mice. GFR was increased in Cav3.2−/− mice with no significant changes in renal plasma flow, heart rate, and blood pressure. Cav3.1−/− mice had a higher renal plasma flow compared with WT mice, whereas GFR was indistinguishable from WT mice. No difference in the concentration response to K+ was observed in isolated afferent and efferent arterioles from Cav3.1−/− mice compared with WT mice. Heart rate was significantly lower in Cav3.1−/− mice compared with WT mice with no difference in blood pressure. T-type antagonists significantly inhibited the constriction of human intrarenal arteries in response to a small depolarization. In conclusion, Cav3.2 channels support dilatation of efferent arterioles and affect GFR, whereas Cav3.1 channels in vivo contribute to renal vascular resistance. It is suggested that endothelial and nerve localization of Cav3.2 and Cav3.1, respectively, may account for the observed effects.

scholarly journals A Pilot Study to Evaluate Renal Hemodynamics in Cirrhosis by Simultaneous Glomerular Filtration Rate, Renal Plasma Flow, Renal Resistive Indices and Biomarkers Measurements

2014 ◽  
Vol 39 (6) ◽  
pp. 543-552 ◽  
Author(s):  
Ayse L. Mindikoglu ◽  
Thomas C. Dowling ◽  
Jade J. Wong-You-Cheong ◽  
Robert H. Christenson ◽  
Laurence S. Magder ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Pilot Study ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Renal Hemodynamics

Renoprotective effects of neuronal NOS-derived nitric oxide and cyclooxygenase-2 metabolites in transgenic rats with inducible malignant hypertension

2008 ◽  
Vol 294 (1) ◽  
pp. F205-F211 ◽  
Author(s):  
Matthew E. Patterson ◽  
John J. Mullins ◽  
Kenneth D. Mitchell
Keyword(s):  
Nitric Oxide ◽  
Renal Plasma Flow ◽  
Renal Hemodynamics ◽  
Normal Diet ◽  
Cyclooxygenase 2 ◽  
Malignant Hypertension ◽  
Similar Extent ◽  
Transgenic Rats ◽  
Cox 2 ◽  
Oxide Synthase

The present study was performed to determine the effects of neuronal nitric oxide synthase (nNOS) and cyclooxygenase-2 (COX-2) inhibition on blood pressure and renal hemodynamics in transgenic rats with inducible ANG II-dependent malignant hypertension [strain name: TGR(Cyp1a1Ren2)]. Male Cyp1a1-Ren2 rats ( n = 7) were fed a normal diet containing indole-3-carbinol (I3C; 0.3%) for 6–9 days to induce malignant hypertension. Mean arterial pressure (MAP) and renal hemodynamics were assessed in pentobarbital sodium-anesthetized Cyp1a1-Ren2 rats before and during intravenous infusion of the nNOS inhibitor S-methyl-l-thiocitrulline (l-SMTC; 1 mg/h). In hypertensive Cyp1a1-Ren2 rats, l-SMTC increased MAP from 169 ± 3 to 188 ± 4 mmHg ( P < 0.01), which was a smaller increase than in noninduced rats (124 ± 9 to 149 ± 9 mmHg, P < 0.01, n = 5). Additionally, l-SMTC decreased renal plasma flow (RPF) to a similar extent (−34 ± 13 vs. −35 ± 12%) in the hypertensive and normotensive rats (4.1 ± 0.2 to 2.7 ± 0.5 and 3.1 ± 0.3 to 2.0 ± 0.3 ml·min−1·g−1, respectively, P < 0.01) but did not alter glomerular filtration rate (GFR) in either group. In additional experiments, administration of the COX-2 inhibitor, nimesulide (3 mg/kg iv), during simultaneous infusion of l-SMTC decreased MAP in both hypertensive and noninduced rats (182 ± 2 to 170 ± 3 mmHg and 153 ± 3 to 140 ± 3 mmHg, respectively, P < 0.01). Nimesulide also decreased RPF (1.9 ± 0.2 to 0.8 ± 0.1 ml·min−1·g−1, P < 0.01) and GFR (0.9 ± 0.1 to 0.4 ± 0.1 ml·min−1·g−1, P < 0.01) in hypertensive rats but did not alter RPF or GFR in noninduced rats. The present findings demonstrate that both nNOS-derived NO and COX-2 metabolites exert pronounced renal vasodilator influences in hypertensive Cyp1a1-Ren2 rats. The data also indicate that the renal vasodilator effects of COX-2-derived prostanoids in hypertensive Cyp1a1-Ren2 rats are not dependent on nNOS activity.

Cyclooxygenase-2 inhibition normalizes arterial blood pressure in CYP1A1-REN2 transgenic rats with inducible ANG II-dependent malignant hypertension

2006 ◽  
Vol 291 (3) ◽  
pp. F612-F618 ◽  
Author(s):  
Allison L. Opay ◽  
Cynthia R. Mouton ◽  
John J. Mullins ◽  
Kenneth D. Mitchell
Keyword(s):  
Blood Pressure ◽  
Renal Plasma Flow ◽  
Renal Hemodynamics ◽  
Malignant Hypertension ◽  
Hypertensive Rats ◽  
Transgenic Rats ◽  
Arterial Blood ◽  
Cox Inhibitor ◽  
Cox 2 ◽  
Cox 1

The present study was performed to determine the effects of cyclooxygenase (COX)-1 and COX-2 inhibition on blood pressure and renal hemodynamics in transgenic rats with inducible malignant hypertension [strain name: TGR(Cyp1a1Ren2)]. Male Cyp1a1-Ren2 rats ( n = 7) were fed a normal diet containing the aryl hydrocarbon, indole-3-carbinol (I3C; 0.3%), for 6–9 days to induce malignant hypertension. Mean arterial pressure (MAP) and renal hemodynamics were measured in pentobarbital sodium-anesthetized Cyp1a1-Ren2 rats during control conditions, following administration of the COX-2 inhibitor nimesulide (3 mg/kg iv), and following administration of the nonspecific COX inhibitor meclofenamate (5 mg/kg iv). Rats induced with I3C had higher MAP than noninduced rats ( n = 7; 188 ± 6 vs. 136 ± 4 mmHg, P < 0.01). There was no difference in renal plasma flow (RPF) or glomerular filtration rate (GFR) between induced and noninduced rats. Nimesulide elicited a larger decrease in MAP in hypertensive rats (188 ± 6 to 140 ± 8 mmHg, P < 0.01) than in normotensive rats (136 ± 4 to 113 ± 8 mmHg, P < 0.01). Additionally, nimesulide decreased GFR (0.9 ± 0.13 to 0.44 ± 0.05 ml·min−1·g−1, P < 0.05) and RPF (2.79 ± 0.27 to 1.35 ± 0.14 ml·min−1·g−1, P < 0.05) in hypertensive rats but did not alter GFR or RPF in normotensive rats. Meclofenamate further decreased MAP in hypertensive rats (to 115 ± 10 mmHg, P < 0.05) but did not decrease MAP in normotensive rats. Meclofenamate did not alter GFR or RPF in either group. These findings demonstrate that COX-1- and COX-2-derived prostanoids contribute importantly to the development of malignant hypertension in Cyp1a1-Ren2 transgenic rats. The data also indicate that COX-2-derived vasodilatory metabolites play an important role in the maintenance of RPF and GFR following induction of malignant hypertension in Cyp1a1-Ren2 transgenic rats.

Interaction between angiotensin II and nitric oxide in control of renal hemodynamics in conscious dogs

1994 ◽  
Vol 267 (6) ◽  
pp. R1472-R1478 ◽  
Author(s):  
A. M. Alberola ◽  
F. J. Salazar ◽  
T. Nakamura ◽  
J. P. Granger
Keyword(s):  
Nitric Oxide ◽  
Glomerular Filtration Rate ◽  
Angiotensin Ii ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Nitric Oxide Synthesis ◽  
Afferent Arterioles ◽  
Renal Vascular

Recent in vitro studies have provided evidence that the vasoconstrictor actions of angiotensin II on afferent arterioles are enhanced by nitric oxide synthesis inhibition. Although these studies suggest that nitric oxide may play a role in protecting the afferent arterioles from angiotensin II-induced vasoconstriction, the importance of this interaction in the regulation of glomerular filtration rate and renal blood flow in the intact, conscious animal is not known. The objective of the present study was to determine the role of nitric oxide in modulating the renal hemodynamic and excretory effects of angiotensin II. Angiotensin II was infused at rates of 0.5, 1.0, and 2.0 micrograms.kg-1.min-1 intrarenally in conscious, chronically instrumented dogs in both the presence and absence of nitric oxide synthesis inhibition by continuous intrarenal infusion of NG-nitro-L-arginine methyl ester (3 micrograms.kg-1.min-1). At a dose of 0.5 micrograms.kg-1.min-1, angiotensin II decreased renal plasma flow by 19%, while having no effect on glomerular filtration rate in control dogs. In contrast, angiotensin II decreased renal plasma flow by 54%, glomerular filtration rate by 40%, and increased renal vascular resistance by 125% in the presence of intrarenal nitric oxide synthesis blockade. At doses of 1.0 and 2.0 micrograms.kg-1.min-1, angiotensin II reduced renal plasma flow by 36 and 45%, glomerular filtration rate by 17 and 23%, and increased renal vascular resistance by 80 and 120%, respectively, in control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Renal Function Testing by External Double Isotope Monitoring Technique

1971 ◽  
Vol 10 (01) ◽  
pp. 16-24
Author(s):  
J. Fog Pedersen ◽  
M. Fog Pedersen ◽  
Paul Madsen
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Correlation Coefficients ◽  
Feedback System ◽  
Effective Renal Plasma Flow ◽  
Advantages And Disadvantages

SummaryAn accurate catheter-free technique for clinical determination simultaneouslyof glomerular filtration rate and effective renal plasma flow by means of radioisotopes has been developed. The renal function is estimated by the amount of radioisotopes necessary to maintain a constant concentration in the patient’s blood. The infusion pumps are steered by a feedback system, the pumps being automatically turned on when the radiation measured over the patient’s head falls below a certain preset level and turned off when this level is again readied. 131I-iodopyracet was used for the estimation of effective renal plasma flow and125I-iothalamate estimation of the glomerular filtration rate. These clearances were compared to the conventional bladder clearances and good correlation was found between these two clearance methods (correlation coefficients 0.97 and.90 respectively). The advantages and disadvantages of this new clearance technique are discussed.

RENAL FUNCTION AND KIDNEY SIZE FOLLOWING HYPOPHYSECTOMY IN MAN

1965 ◽  
Vol 48 (3) ◽  
pp. 348-354 ◽  
Author(s):  
Thomas Falkheden ◽  
Ingmar Wickbom
Keyword(s):  
Renal Function ◽  
Diabetic Retinopathy ◽  
Glomerular Filtration Rate ◽  
Plasma Flow ◽  
Mammary Carcinoma ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Kidney Weight ◽  
Kidney Size ◽  
Before And After

ABSTRACT Measurements of glomerular filtration rate (GFR) and renal plasma flow (RPF) were performed in close connection with roentgenographic estimation of kidney size, before and after hypophysectomy, in 10 patients (four cases of metastatic mammary carcinoma, five cases of diabetic retinopathy and one case of acromegaly). Hypophysectomy was regularly followed by a decrease in GFR and RPF. In most cases, a reduction in the roentgenographic kidney size was also observed. However, the changes in the roentgenographic kidney size and calculated kidney weight after hypophysectomy were smaller and occurred at a slower rate than the alterations in GFR and RPF. The results favour the view that, primarily, the decrease in GFR and RPF following hypophysectomy is essentially functional rather than due to a reduced kidney mass.

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