ascorbic-acid and Hypertension--Renal

To investigate whether the administration of the anti-oxidant vitamin C could prevent the systemic and renal effects of nicotine in healthy non-smoker volunteers.. The acute effects of oral, 4 mg, nicotine gum (n = 10), intravenous vitamin C (12 mmol, n = 8) or both (n=9) on mean arterial pressure (MAP), heart rate, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and urinary cyclic guanosine monophosphate (cGMP) were assessed in non-smokers.. In subjects receiving nicotine, MAP (+8 +/- 4 mmHg, P<0.0001) and HR (+13 +/- 8 beats/min, P < 0.001) increased whereas ERPF (-65 +/- 69 ml/min per 1.73 m2, P < 0.01), GFR (-14.5 +/- 16.8 ml/min per 1.73 m2, P < 0.01) and cGMP (-180 +/- 173 pmol/min, P < 0.01) decreased as compared to baseline values. The concomitant administration of nicotine and vitamin C caused similar haemodynamic changes; however, cGMP remained unchanged. In subjects receiving only vitamin C, there were no significant changes in MAP, heart rate, ERPF, GFR and cGMP.. The present findings indicate that vitamin C was unable to prevent the renal vasoconstriction, but it prevented the fall in cGMP provoked by nicotine in non-smokers. This suggests that nicotine induces a degradation of nitric oxide mediated by oxygen-derived free radicals which may be prevented by vitamin C administration. The nicotine-induced renal vasoconstriction may be related to other mechanism(s).

Topics: Adult; Antioxidants; Ascorbic Acid; Blood Pressure; Cyclic GMP; Female; Glomerular Filtration Rate; Heart Rate; Humans; Hypertension, Renal; Male; Nicotine; Nicotinic Agonists; Renal Circulation; Smoking

Impaired relaxation induced by the new nitric oxide (NO) donor [Ru(NH.NHq)(terpy)NO(+)](3+) (TERPY) has been observed in the aortic rings from renal hypertensive rats (2K-1C). An increased production of reactive oxygen species (ROS) in the aortas from 2K-1C rats are capable of reducing NO bioavailability. Therefore, this study aimed at investigating the effects of an antioxidant (vitamin C) on the relaxant effect of NO released from TERPY on the 2K-1C rat aorta. As for vascular reactivity, the potency of TERPY is greater in the control rats (2K) than in 2K-1C whereas the maximum relaxation (ME) is not significantly different between the 2K and 2K-1C rat aortas. The relaxation of TERPY is potentiated only in the 2K-1C aortic ring treated with vitamin C. TERPY has a lower effect in decreasing cytosolic Ca(2+) concentration ([Ca(2+)]c) in vascular smooth muscle cells (VSMCs) from 2K-1C rats. This effect is also potentiated in 2K-1C aortic cells treated with vitamin C, but it is not altered in 2K cells. The basal cytosolic NO concentration ([NO]c) is lower in 2K-1C than in 2K cells, and the bioavailability of the NO released from TERPY is larger in 2K than in 2K-1C VSMCs. The superoxide radical concentration ([O(2)(*-)]) is higher in the 2K-1C aorta, and vitamin C reduces the [O(2)(*-)] in the 2K-1C aorta. Taken together, these results show that in the aortas of renal hypertensive 2K-1C rats, released NO from the new NO donor is not available to produce a similar effect in 2K aorta due to increased [O(2)(*-)].

Topics: Animals; Aorta; Ascorbic Acid; Calcium; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Hypertension, Renal; Kidney; Male; Muscle, Smooth, Vascular; Nitric Oxide; Nitric Oxide Donors; Organ Culture Techniques; Organometallic Compounds; Phenylephrine; Rats; Rats, Wistar; Ruthenium; Superoxides; Time Factors; Vasodilation

Spontaneously hypertensive rats (SHR) are born normotensive and develop hypertension (HTN) later in life (age 4 to 5 weeks). HTN in SHR is associated with and caused in part, by oxidative stress and renal interstitial inflammation. This study tested the hypothesis that lifelong antioxidant supplementation beginning at prenatal period may delay the onset and reduce the severity of HTN in SHR. The study further sought to explore the effect of diet modification on renal tissue NAD(P)H oxidase and calcineurin abundance.. Pregnant SHR and their offspring were fed either an antioxidant-fortified diet (a chow containing alpha-tocopherol 5000 IU/kg, ascorbic acid 500 ppm, selenium 2.76 ppm, and zinc 350 ppm) or regular diet (alpha-tocopherol 40 IU/kg, selenium 0.2 ppm, and zinc 70 ppm). Animals were observed for 24 weeks. Wistar-Kyoto rats fed either a regular or antioxidant diet served as control.. Onset of HTN was delayed and severity of HTN was reduced in antioxidant-treated compared with untreated SHR. Markers of oxidative stress (i.e., plasma hydrogen peroxide, renal tissue malondialdehyde, and nitrotyrosine abundance) were elevated in untreated but not in antioxidant-treated SHR. gp91phox and p22phox subunits of NAD(P)H oxidase were markedly elevated in the renal cortex of untreated SHR and partially restored in the treated SHR. Similarly, renal calcineurin Aalpha and B subunits were elevated in untreated SHR and were partially restored in the treated SHR. Antioxidant therapy had no effect on the measured parameters in the WKY control.. Lifelong consumption of antioxidant-rich diet ameliorates HTN and oxidative stress in SHR. This is associated with the reduction of superoxide-generating enzyme, NAD(P)H oxidase, and immunoregulatory factor calcineurin. Antioxidant-rich diet appears to attenuate oxidative stress, not only by fortifying antioxidant defense capacity but also by lowering NAD(P)H oxidase, which is a major source of reactive oxygen species.

Topics: alpha-Tocopherol; Animal Feed; Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Calcineurin; Female; Food, Fortified; Hypertension, Renal; Kidney; NADPH Oxidases; Oxidative Stress; Pregnancy; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Selenium; Up-Regulation

Endogenous ouabain-like factors (OLF) may play a role in the pathogenesis of volume-dependent hypertension by raising intracellular free calcium ([Ca2+]i) as a consequence of inhibition of the sodium pump. In previous studies we described the presence of two low molecular (Mr approximately equals 400) inhibitors of Na-K-ATPase in human urine, ie, a more polar OLF-1 and a more apolar OLF-2. We subsequently identified the active compound in OLF-2 as vanadium (V(IV))-diascorbate (Mr 416). OLF-1, OLF-2, and V-diascorbate inhibited dose-dependently porcine Na-K-ATPase in vitro. In the present study we investigated the effects of urinary OLF-1, OLF-2, and V-diascorbate on calcium mobilization, ie, on [Ca2+]i in cultured rat vascular smooth muscle (VSM) cells in comparison to the effects of ouabain, angiotensin II (A II), and arginine-vasopressin (AVP). [Ca2+]i was determined by the fura-2 method. OLF-1 and OLF-2 (each approximately equals 10(-4) mol/L), obtained as single spots by thin-layer chromatography, produced a rise in [Ca2+]i in VSM cells from 45 +/- 7 to 99 +/- 22 and from 48 +/- 9 to 92 +/- 2 nmol/L (each n = 5; P < .05), respectively, after 3 min. V-diascorbate also increased [Ca2+]i slowly and dose-dependently, eg, from 56 +/- 14 to 102 +/- 15 nmol/L at a concentration of 10(-6) mol/L (n = 5; P < .05) after 3 min. A similar slow rise in [Ca2+]i from 53 +/- 10 to 185 +/- 3 nM (n = 5; P < .05) after 3 min was found with ouabain (10(-6) mol/L). As standard vasoconstrictor, All (10(-8) mol/L) rapidly increased [Ca2+]i from 23 +/- 4 to 846 +/- 50 nmol/L (n = 7; P < .01) within 30 sec. This effect was enhanced to 1,389 +/- 161 nM (n = 7; P < .01) when VSM cells were preincubated with V-diascorbate (10(-6) mol/L) for 10 min. AVP (10(-7) mol/L) also rapidly increased [Ca2+]i to 418 +/-11 nmol/L within 30 sec (n = 7; P < .01). This effect was enhanced in the presence of OLF-2 (approximately equals 10(-4) mol/L) or ouabain (10(-6) mol/L) to 523 +/- 14 and 560 +/- 19 nmol/L, respectively (each n = 7); P < .01). The calcium channel blocker verapamil, the intracellular calcium release blocker TMB-8, and the unselective cation channel blocker Ni2+ partly blunted the A II- or AVP-induced rise in [Ca2+]i and prevented the OLF-2- and V-diascorbate-induced increase in [Ca2+]i. Thus, OLF-1, OLF-2 and V-diascorbate, the active component of OLF-2, reveal effects similar to those of ouabain on [Ca2+]i in VSM cells, ie, they produce a slow rise in [Ca2+]i subsequent to in

Topics: Adult; Angiotensin II; Animals; Aorta, Thoracic; Arginine Vasopressin; Ascorbic Acid; Biological Factors; Biological Transport; Calcium; Calcium Channel Blockers; Cardenolides; Cells, Cultured; Digoxin; Enzyme Inhibitors; Gallic Acid; Humans; Hypertension, Renal; Male; Muscle, Smooth, Vascular; Nickel; Organometallic Compounds; Ouabain; Rats; Saponins; Sodium-Potassium-Exchanging ATPase; Vasoconstrictor Agents; Verapamil

99mTc-Phosphomycin, a new radiopharmaceutical for kidney visualization, was used for animal experiments and tests of 171 patients. The results confirmed the usefulness of this product. The ease and yield of the labelling procedure, the low cost of the product, the excellent quality of the images and the functional information obtained showed that the use of 99mTc-phosphomycin as a radiopharmaceutical for kidney visualization has many advantages.

Topics: Adolescent; Adult; Aged; Animals; Anti-Bacterial Agents; Aprotinin; Ascorbic Acid; Chromatography, Paper; Female; Fosfomycin; Humans; Hypertension, Renal; Intestines; Kidney; Kidney Failure, Chronic; Kinetics; Liver; Male; Mice; Middle Aged; Organotechnetium Compounds; Rabbits; Radionuclide Imaging; Technetium; Time Factors

Topics: Animals; Ascorbic Acid; Chronic Disease; Citrates; Drug Therapy, Combination; Hydronephrosis; Hypertension, Renal; Ketoglutaric Acids; Kidney; Malates; Oxidative Phosphorylation; Pyelonephritis; Rats; Solutions; Succinates

Topics: Adult; Aged; Aneurysm; Ascorbic Acid; Female; Glomerular Filtration Rate; Humans; Hydronephrosis; Hypertension, Renal; Iodine Radioisotopes; Iodohippuric Acid; Isotope Labeling; Kidney; Kidney Calculi; Kidney Diseases, Cystic; Kidney Neoplasms; Male; Middle Aged; Pyelonephritis; Quality Control; Radioisotope Renography; Renal Artery; Renal Artery Obstruction; Technetium; Urinary Calculi

Topics: Adenocarcinoma; Aged; Angiography; Ascorbic Acid; Humans; Hypertension, Renal; Indium; Iron; Kidney Diseases, Cystic; Kidney Neoplasms; Male; Middle Aged; Pentetic Acid; Photography; Radioisotopes; Technetium

Topics: Arteriosclerosis; Ascorbic Acid; Cholesterol; Coronary Vessels; Humans; Hypercholesterolemia; Hypertension; Hypertension, Renal; Kidney; Vitamins