Endogenous nitric oxide(NO) plays an important role in the regulation of blood pressure. It has been known that the evoked NO-dependent dilator system may be impaired in various hypertensive models. The effects of NG-nitro-L-arginine(L-NNA), lipopolysaccharide(LPS) and tempol on mean arterial pressure(MAP) and the effects of L-NNA on isolated aorta tone were studied in order to elucidate potential alterations in resting vasodilator tone of NO in two-kidney, one clip(2K1C) hypertension. Plasma nitrite/nitrate levels were measured by colorimetric assay, and the expression of endothelial and inducible NO synthases(eNOS, iNOS) was determined by Western blot analysis. L-NNA caused an increase of MAP, while LPS produced a hypotensive effect in both 2K1C and control rats. The magnitude of the pressor or depressor response to L-NNA and LPS was comparable in the two groups. Tempol induced a sustained decrease in MAP in 2K1C rats, while it had no effects on MAP in control rats. Plasma concentrations of NO metabolites were significantly increased following the LPS-treatment in both 2K1C and control rats, while they were not affected by tempol-treatment. In endothelium-intact aortic rings precontracted with 25 mM KCl, L-NNA caused a dose-dependent contraction. The magnitude of the maximal contraction was attenuated in 2K1C rats as compared with control. An inhibition of contractile responses to L-NNA in the hypertensive group was also shown in rubbed rings, although the magnitude of contractions was markedly reduced. The vascular expression of both eNOS and iNOS was significantly decreased in 2K1C rats as compared with control. These results indicate that 2K1C hypertension is associated with a reduced basal vasodilator tone of NO and a decrease in the vascular expression of NOS isozymes.
Animals ; Aorta ; Blood Pressure ; Blotting, Western ; Hypertension ; Isoenzymes ; Nitric Oxide* ; Plasma ; Rats*

The monitoring of airway inflammation has assessed in bronchial asthma directly by sputum examination, and indirectly by measurements in peripheral blood. To investigate the diagnostic value of these two methods, we compared nitric oxide (NO) metabolites, eosinophils, and eosinophil cationic protein (ECP) in sputum and blood in patients with asthma and control subjects. Sputum and serum were obtained from fifteen patients with asthma, and then were examined before anti-asthma treatment, including steroid preparations. ECP was measured by fluoroimmunoassay. NO metabolites were assayed by using modified Griess reaction. Asthmatic patients, compared with control subjects, had significantly higher level of NO metabolites, higher proportion of eosinophils, and higher levels of ECP in sputum. Asthmatic patients, compared with control subjects, however, had significantly higher number of eosinophils, and were at higher levels of ECP in blood. FEV1, FEV1 /FVC was negatively correlated with sputum eosinophils. The area under receiver operating characteristic(ROC) curve showed that eosinophils in sputum are significantly accurate markers than NO metabolites in sputum and blood. These findings suggest that the proportion of eosinophils in sputum have more accurate diagnostic marker of asthmatic airway inflammation than NO metabolites in sputum in differentiating asthmatic patients from control subjects.
Adult ; Area Under Curve ; Asthma/*blood/*metabolism ; Blood Proteins/*metabolism ; Comparative Study ; Eosinophils/*metabolism ; Female ; Fluoroimmunoassay ; Human ; Inflammation ; Male ; Nitrates/metabolism ; Nitric Oxide/blood/*metabolism ; Nitrites/metabolism ; ROC Curve ; Ribonucleases/blood/*metabolism ; Sputum/*metabolism

BACKGROUND AND OBJECTIVES: Protein tyrosine kinases appear to be involved in the signal transduction mechanisms, which result in vascular smooth muscle contraction, as well those required in cell growth. The present study was conducted to examine the role of tyrosine kinases in the norepinephrine-induced vascular smooth muscle contraction of isolated aortae from two-kidney, one clip (2K1C) hypertensive rats. MATERIALS AND METHODS: 2K1C hypertension was made by clipping the left renal artery of the rats, with age-matched rats receiving a sham treatment serving as controls. Thoracic aortae denuded of endothelium were mounted in tissue baths to measure the isometric tension. RESULTS: The putative tyrosine kinase inhibitors, genistein and tyrphostin 25, significantly inhibited the contractile responses of the aorta to norepinephrine in the control rats, but not in the 2K1C rats. The protein tyrosine phosphatase inhibitor, sodium orthovanadate, selectively potentiated the contractile response to norepinephrine, but only in the controls. Genistein, tyrphostin 25 and sodium orthovanadate did not affect KCl-induced vascular contractions in either the 2K1C or the controls. The vascular contraction elicited by phorbol 12, 13 dibutyrate, in the presence and absence of genistein, did not alter in either the 2K1C or the controls. CONCLUSION: These findings indicate that protein tyrosine kinases participate in the norepinephrine-induced contraction of rat aortic smooth muscle, where the role is attenuated in 2K1C renal hypertension.
Animals ; Aorta ; Aorta, Thoracic ; Baths ; Endothelium ; Genistein ; Hypertension ; Hypertension, Renal ; Muscle, Smooth ; Muscle, Smooth, Vascular ; Norepinephrine ; Phosphotransferases* ; Placebos ; Protein Tyrosine Phosphatases ; Protein-Tyrosine Kinases ; Rats* ; Renal Artery ; Signal Transduction ; Sodium ; Tyrosine* ; Vanadates

PURPOSE: The present study was aimed to examine whether caffeine alters the local regulation of atrial natriuretic peptide(ANP) and nitric oxide(NO) systems in the kidney. METHODS: Male Sprague-Dawley rats were treated with caffeine, consisting of a single oral bolus(0.2%, 1 mL/kg) followed by supplementation in drinking water(0.2%) for 1 day. Rats treated the same without caffeine served as control. The tissue expression of ANP mRNA was determined by reverse transcription-polymerase chain reaction. Tissue levels of nitrite/nitrate were determined. The expression of aquaporin(AQP)-1 and AQP2 proteins was determined by Western blot analysis. RESULTS: Following the treatment with caffeine, the expression of ANP mRNA was increased in the kidney. The renal tissue nitrite/nitrate level was also increased by caffeine-treatment. On the other hand, the expression of AQP1 and AQP2 proteins was not significantly altered. CONCLUSION: The enhanced activities of local ANP and NO systems may in part be causally related with the caffeine-induced natriuresis and diuresis, while AQP channels are not involved.
Animals ; Aquaporin 2 ; Atrial Natriuretic Factor ; Blotting, Western ; Caffeine* ; Diuresis ; Drinking ; Hand ; Humans ; Kidney ; Male ; Natriuresis ; Nitric Oxide* ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger

BACKGROUND: Although being associated with an elevated plasma atrial natriuretic peptide(ANP), its precise role in the postobstructive diuresis has not been fully understood. Evidence has been provided suggesting that the locally-synthesized ANP in the kidney contributes to the regulation of urinary sodium excretion. The present study was aimed to investigate whether an altered regulation of local ANP system is involved in the postobstructive diuresis. METHODS: Male Sprague-Dawley rats were used. Both proximal ureters were ligated for 48 hours, after which the kidneys were taken without releasing the ligature, being designated as bilateral ureteral obstruction(BUO) group; or the ligature was released and 4 or 24 hr later, urinary data were collected, being designated as BUR-4 or BUR-24, respectively. Sham operated rats were used as control. Plasma ANP levels were determined by radioimmunoassay. The expression of ANP and natriuretic peptide receptor(NPR)-A mRNAs was determined by reverse transcription-polymerase chain reaction(RT-PCR). To further examine whether the altered renal ANP system, if any, was associated with an altered biological effects of guanylyl cyclase, ANP-stimulated cGMP accumulation was determined in membrane preparations of the glomeruli and papillae by radioimmunoassay. RESULTS: The plasma ANP level was increased in BUO group compared with that in the control(260.5+/-32.5 vs. 133.3+/-23.5pg/mL, p<0.05), decreased in BUR-4 group(3.6+/-0.5 vs. 143.5+/-42.8pg/mL, p<0.01), while not significantly different in BUR-24 group. In BUR-4. the urinary flow rate increased compared with that in the control(1598+/-370 vs. 215+/-34 microL/hr, p<0.01), along with increases of FENa(11.5+/-4.1 vs. 0.25+/-0.02%, p<0.05) and UNaV (153.7+/-23.7 vs. 36.5+/-9.3microEq/hr, p<0.01). In BUR-24, the urinary parameters were normalized. Renal tissue expression of ANP mRNA was increased in BUO as well as in BUR-4, while not changed in BUR-24. NPR-A mRNA expression was decreased in the kidney of BUO. The ANP-stimulated accumulation of cGMP in the isolated glomeruli and papillae in BUO was significantly reduced. The guanylyl cyclase activities were partly recovered in BUR-4 and completely in BUR-24. CONCLUSION: An enhanced local activity of ANP in the kidney may be causally related to the postobstructive diuresis.
Animals ; Atrial Natriuretic Factor ; Diuresis ; Guanylate Cyclase ; Humans ; Kidney* ; Ligation ; Male ; Membranes ; Plasma ; Radioimmunoassay ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger ; Sodium ; Ureter

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. There are some reports in the literature concerning unilateral ADPKD. However, in adults, only a few cases of unilateral ADPKD with agenesis of contralateral kidney have been reported. We present a case of unilateral ADPKD with agenesis of contralateral kidney in a 66-yr-old man. Radiographic images showed the enlarged right kidney with multiple variable-sized cysts and the absence of the left kidney. The diagnosis of ADPKD was confirmed by the family screening. The patient received maintenance hemodialysis for endstage renal disease. We report a case of unilateral ADPKD associated with contralateral renal agenesis in a 66-yr-old male patient with a literature review.
Abdomen/pathology ; Aged ; Female ; Human ; Kidney/abnormalities* ; Male ; Pedigree ; Polycystic Kidney, Autosomal Dominant/diagnosis* ; Polycystic Kidney, Autosomal Dominant/pathology* ; Polycystic Kidney, Autosomal Dominant/physiopathology ; Radiopharmaceuticals/metabolism ; Technetium Tc 99m Dimercaptosuccinic Acid/metabolism

BACKGROUND: Cells rely on gap junctions for intercellular communication, which is important for growth and contractility. The present study was conducted to test the hypothesis that contractile responses in aortic rings from two-kidney, one clip (2K1C) hypertensive rats are more dependent on gap junctional communication compared to those from normotensive rats. METHODS: 2K1C hypertension was induced by clipping the left renal artery and age-matched rats received a sham operation. Heptanol and octanol were used as inhibitors of gap junctional activity. RESULTS: The contraction induced by phenylephrine or KCl was completely reversed by either heptanol or octanol, and the relaxant response to inhibitors was more enhanced in 2K1C hypertensive rats compared to sham-operated rats. Vessels from hypertensive rats also relaxed more to nifedipine when precontracted with KCl, although it did not differ in aortic segments contracted with phenylephrine in between normotensive and hypertensive rats. CONCLUSION: These results suggest that gap junctional communication and voltage-operated calcium channels are differentially regulated in 2K1C renal hypertension.
Rats ; Animals

BACKGROUND: Cells rely on gap junctions for intercellular communication, which is important for growth and contractility. The present study was conducted to test the hypothesis that contractile responses in aortic rings from two-kidney, one clip (2K1C) hypertensive rats are more dependent on gap junctional communication compared to those from normotensive rats. METHODS: 2K1C hypertension was induced by clipping the left renal artery and age-matched rats received a sham operation. Heptanol and octanol were used as inhibitors of gap junctional activity. RESULTS: The contraction induced by phenylephrine or KCl was completely reversed by either heptanol or octanol, and the relaxant response to inhibitors was more enhanced in 2K1C hypertensive rats compared to sham-operated rats. Vessels from hypertensive rats also relaxed more to nifedipine when precontracted with KCl, although it did not differ in aortic segments contracted with phenylephrine in between normotensive and hypertensive rats. CONCLUSION: These results suggest that gap junctional communication and voltage-operated calcium channels are differentially regulated in 2K1C renal hypertension.
Rats ; Animals

BACKGROUND: Chronic treatment with the dietary flavonoid quercetin is known to lower blood pressure and restore endothelial dysfunction in animal models of hypertension. This study investigated the direct effects of quercetin on vascular response in chronic 2-kidney, 1-clip (2K1C) renal hypertensive rats. The effects of antioxidant vitamin ascorbic acid on the vasoreactivity were also examined. METHODS: 2K1C renal hypertension was induced by clipping the left renal artery; age-matched rats that received sham treatment served as controls. Thoracic aortae were mounted in tissue baths for the measurement of isometric tension. RESULTS: Relaxant responses to acetylcholine were significantly attenuated in 2K1C rats in comparison with sham rats. Quercetin or ascorbic acid augmented acetylcholine-induced relaxation in 2K1C rats, whereas no significant differences were noted in sham rats. The relaxation response to sodium nitroprusside was comparable between 2K1C and sham rats, and sodium nitroprusside-induced relaxation was not altered by quercetin or ascorbic acid in either group. The contractile response to phenylephrine was significantly enhanced in 2K1C rats compared with sham rats. Phenylephrine-induced contraction was inhibited by pretreatment with quercetin or ascorbic acid in 2K1C rats, whereas neither chemical affected responses in sham rats. N(w)-nitro-L-arginine methyl ester markedly augmented the contractile response to phenylephrine in sham rats, whereas no significant differences were observed in 2K1C rats. Quercetin or ascorbic acid did not affect phenylephrine-induced contraction in the presence of N(w)-nitro-L-arginine methyl ester in either 2K1C or sham rats. CONCLUSION: Acute exposure to quercetin appears to improve endothelium-dependent relaxation and inhibit the contractile response, similar to the effect of ascorbic acid in 2K1C hypertension. These results partially explain the vascular beneficial effects of quercetin in renal hypertension.
Acetylcholine ; Animals ; Aorta* ; Aorta, Thoracic ; Ascorbic Acid ; Baths ; Blood Pressure ; Hypertension ; Hypertension, Renal ; Models, Animal ; Nitroprusside ; Phenylephrine ; Placebos ; Quercetin* ; Rats* ; Relaxation ; Renal Artery ; Sodium ; Vitamins

The present study was aimed at investigating whether FK506 alters the regulation of nitric oxide(NO) system. Male Sprague-Dawley rats were treated with FK506(1 mg/kg/day, i.m.) for 3 weeks. Control group was without treatment of FK506. Plasma levels and urinary excretion of NO metabolites(nitrite/nitrate, NOx) were measured. The protein expression of NO synthases(NOS) and tissue contents of NOx were determined in the kidney and thoracic aorta. The aorta was also examined of its changes in isometric tension in responses to acetylcholine and sodium nitroprusside. The arterial pressure did not significantly differ between FK506-treated and control groups. Plasma NOx levels remained unaltered, while urinary NOx excretion was significantly decreased in FK 506-treated group. Tissue contents of NOx were significantly decreased, although the expression of ecNOS and iNOS proteins was significantly altered neither in the kidney nor in the aorta. Acetylcholine-induced relaxation of the isolated aortic ring was significantly attenuated, whereas sodium nitroprusside-induced relaxation was not significantly affected. These results suggest that FK506 decreases the tissue contents of NO, without significantly affecting the expression of NOS.
Acetylcholine ; Animals ; Aorta ; Aorta, Thoracic ; Arterial Pressure ; Humans ; Kidney ; Male ; Nitric Oxide* ; Nitroprusside ; Plasma ; Rats* ; Rats, Sprague-Dawley ; Relaxation ; Sodium ; Tacrolimus*