Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of the renal kallikrein-kinin system in the regulation of renal function is not completely understood. Intrarenal kinins can influence renal function by acting as paracrine hormones at basolateral, luminal, or both sites in the distal nephron. To examine the role of intrarenal kinins in deoxycorticosterone acetate-salt-treated rats, which have high renal kallikrein, Fab fragments of antibradykinin antibody or DArg[Hyp3Thi5,8DPhe7]bradykinin, a kinin antagonist, were used to block kinins. At the dose used, the antibody (25 mg) and kinin antagonist (10 micrograms/min/rat) inhibited the hypotensive effect of intra-arterially injected bradykinin (100 ng) by 70% and 52%, respectively. The antibody appeared in the urine within 30 minutes after administration. Urinary volume was lowered from 9.4 +/- 0.2 to 6.7 +/- 0.4 microliters/min/g kidney wt (p less than 0.001, paired t test) by the antibody and from 8.5 +/- 0.3 to 6.8 +/- 0.4 microliters/min/g kidney wt (p less than 0.004, paired t test) by the kinin antagonist. The antibody lowered urine sodium excretion from 1.11 +/- 0.04 to 0.88 +/- 0.06 mueq/min/g kidney wt (p less than 0.001, paired t test), whereas the kinin antagonist had no significant effect. Neither altered blood pressure, renal blood flow, or glomerular filtration rate. These data suggest that in deoxycorticosterone acetate-salt-treated rats, excretion of water and sodium is regulated in part by kinins. The antidiuretic effect of the antibody and kinin antagonist might be due to blockade of kinins in the vascular-interstitial space of the kidney, since the kinin antagonist is likely hydrolyzed in the proximal tubule and does not reach the lumen of the distal nephron.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Jun
PMID:Renal effects of Fab fragments of kinin antibodies on deoxycorticosterone acetate-salt-treated rats. 235 28

The effect of progressive increases in intraluminal glucose concentration on proximal tubule sodium absorption was studied in normal and streptozotocin diabetic rats by microperfusion. Each tubule was perfused twice, with and without glucose added to the perfusion fluid. Net sodium and water absorption were markedly enhanced by 300-500 mg% intraluminal glucose in both normal and diabetic rats. Substituting the transported but nonmetabolized glucose analogue, alpha-methyl D-glucoside for glucose also resulted in marked stimulation of sodium absorption, whereas substituting bicarbonate and acetate for chloride in the perfusion solution inhibited the effect of glucose. These observations suggest that the stimulation of sodium absorption by glucose was mediated by the brush border Na/glucose cotransporter. Sodium concentration and osmolality were found to fall markedly to hypotonic levels when high glucose concentrations were in the perfusion fluid. This luminal hypotonicity may be an important driving force for proximal fluid absorption. In poorly controlled diabetes, high filtered glucose concentrations may lead to enhanced proximal sodium and water absorption, which could in turn contribute to volume expansion, hypertension, and renal hypertrophy.
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PMID:Progressive increases in luminal glucose stimulate proximal sodium absorption in normal and diabetic rats. 236 20

It has been recently proposed that 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) is responsible for aldosterone tissue specificity. A 11 beta-OHSD deficiency has been invoked as a cause of the syndrome of apparent mineralocorticoid excess, and 11 beta-OHSD inhibition by liquorice has been invoked to explain the hypertension induced by this drug. Since the renal tubule is composed of aldosterone-sensitive and insensitive segments, we determined the distribution of 11 beta-OHSD along the rabbit tubule. Pools of tubular segments isolated by microdissection were incubated for 2 h at 37 degrees C in the presence of [3H]corticosterone (3H-B, 8.10(-9) M). Afterwards, the amounts of 3H-B and of the metabolite 11-dehydrocorticosterone (3H-A) were determined using HPLC analysis. In the proximal tubule, in either its convoluted or straight portion, and in the medullary thick ascending limb, the amount of 3H-A was 19.6 +/- 3.8% (n = 12), 17.9 +/- 3.4 (n = 8), and 15.0 +/- 2.2 (n = 4), respectively, of the sum of 3H-A + 3H-B. In the cortical ascending limb and the collecting tubule in its cortical and medullary parts, it was 74.7 +/- 6.8% (n = 4), 74.1 +/- 4.9 (n = 9) and 64.6 +/- 14.1 (n = 3), respectively. In both proximal and cortical collecting tubule, addition of carbenoxolone 8.10(-4) M, an inhibitor of 11 beta-OHSD, almost completely inhibited the conversion of 3H-B to 3H-A. Thus, 11 beta-OHSD activity was high in the aldosterone-sensitive segments, and low in the aldosterone-insensitive segments. These results strongly favor the hypothesis that 11 beta-OHSD is a key enzyme in mineralocorticoid tissue specificity along the rabbit nephron. They reinforce the notion that a defect in 11 beta-OHSD plays a major role in the syndrome of apparent mineralocorticoid excess and liquorice-induced hypertension.
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PMID:Distribution of 11 beta-hydroxysteroid dehydrogenase along the rabbit nephron. 239 32

Several laboratories have reported that the activities of sodium-lithium countertransport are increased in red blood cells from patients with essential hypertension. Based on the many similarities between this transport system and the renal sodium-proton exchanger, a hypothesis has been put forth in the literature that increased red blood cell sodium-lithium countertransport activity may be a marker for increased sodium-proton exchange activity in the renal proximal tubule. The present studies were designed to test the hypothesis that sodium-lithium countertransport in red blood cells from humans or rabbits is mediated by the same transport mechanism that mediates sodium-proton exchange in the renal brush border from those species. Similar to what has been reported for the rabbit, the present studies show that an amiloride-sensitive sodium-proton exchanger is present in human renal brush border vesicles. However, Na+-Li+ countertransport in human and rabbit red blood cells, assayed under several different conditions, was not inhibited by amiloride. In agreement with what has been reported for humans, the present studies show that extracellular proton-stimulated sodium efflux is inhibited by amiloride in rabbit red blood cells. These data demonstrate a difference (amiloride sensitivity) between the red blood cell sodium-lithium countertransporter and the renal brush border sodium-proton exchanger in humans and rabbits. These experiments detract from the hypothesis that increased red blood cell sodium-lithium countertransport activity in patients with essential hypertension is a marker for increased sodium-proton exchange activity in the renal brush border.
Hypertension 1987 Jan
PMID:Difference between human red blood cell Na+-Li+ countertransport and renal Na+-H+ exchange. 243 11

The hemodynamic and renal effects of isradipine were investigated in 10 hypertensive patients treated for 3.5 months and in a further nine patients treated for two years. Both groups achieved significant and sustained reductions in systolic blood pressure/diastolic blood pressure (-15 percent/-12 percent and -15 percent/-20 percent, respectively; p less than 0.001). Renal parameters were investigated two to three hours after the morning dose of isradipine, using a water-loading procedure. After 3.5 months of treatment, the glomerular filtration rate and renal plasma flow showed small increases (+6 percent and +9 percent, respectively, p less than 0.05), whereas, after two years, these changes were no longer present (+4 percent and 0 percent). Clearance of sodium and uric acid was increased by 40 percent (p less than 0.01) and 21 percent (p less than 0.01), respectively, after 3.5 months, and by 45 percent (p less than 0.05) and 23 percent (p less than 0.01), respectively, after two years. Lithium clearance studies revealed the natriuretic effect to be located in the proximal tubule. After 3.5 months, a significant relationship was found between the blood pressure response and the change in sodium excretion, but this relationship also was no longer present after two years. In conclusion, because of a maintained blood pressure-lowering effect while preserving renal function, and sustained natriuretic and uricosuric actions, isradipine can be considered a promising agent in the long-term treatment of arterial hypertension.
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PMID:Long-term effects of isradipine on blood pressure and renal function. 252 50

Administration of atriopeptin III (125, 250 and 500 ng/kg, intravenously) into pentobarbitone anaesthetized normotensive and DOCA-salt hypertensive rats had no effect on blood pressure or renal haemodynamics. Urine flow and absolute and fractional sodium excretion were increased by 48-90% from the lowest to the highest dose of atriopeptin III in the normotensive group, but were increased by over twice these amounts in the DOCA-salt hypertensive rats. Fractional lithium excretion and calculated proximal tubular fluid reabsorption were unaffected by the peptide in the normotensive rats, but in the hypertensive group atriopeptide III increased fractional lithium excretion by 25-50% and decreased proximal tubular reabsorption to a similar extent. Beyond the proximal tubule there were similar increases in fractional and absolute fluid handling in both groups of rats. These results demonstrated that in DOCA-salt hypertension there was increased sensitivity to the natriuretic activity of atriopeptin III which appeared to result from an increased responsiveness of the proximal tubule.
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PMID:A comparison of the action of atriopeptin III on renal function in normal and DOCA-salt hypertensive rats. 253 Feb 72

Cadmium exposure is known to induce hypertension, but development of hypertension is not universal in exposed animals. However, the cellular uptake of cadmium could also exert renal cytotoxic effects which have been, until now, essentially only studied at the proximal tubule level. Kallikrein is an enzyme synthetized in renal cortex and excreted in the urine in the distal tubule. Therefore, to evaluate the distal renal effect of cadmium, we studied the daily urinary kallikrein excretion (UKE) in conscious unrestrained female Brown Norway rats during long-term chronic exposure to 2 dosages of cadmium given subcutaneously 3 times a week, a low dose (LD): 0.25 mg/kg and a high dose (HD): 1 mg/kg. Neither dose of cadmium was able to induce significant hypertension in the treated animals. HD administration for 24 weeks resulted in a decreased UKE associated with an increase in plasma renin activity and sodium and potassium excretions. LD administration had no significant effect on UKE. Twenty weeks after stopping cadmium administration, a persistent reduction in UKE was still observed; furthermore, the group which had been previously administered a LD of cadmium, now also exhibited a reduced UKE. During this re-examination period in both groups, the UKE reductions were associated with normal systolic blood pressure, glycosuria, natriuresis. Our data show that cadmium administration can influence UKE, plasma renin activity, plasma aldosterone concentration and electrolyte excretion without inducing any variation of blood pressure. This may reflect a nephrotoxic, non-hypertensive effect. Since this effect persisted after stopping cadmium administration, it may indicate a prolonged irreversible nephrotoxic effect at the distal nephron level. Thus, UKE may be a useful non-invasive index to evaluate distal nephrotoxicity.
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PMID:Renal kallikrein excretion as a distal nephrotoxicity marker during cadmium exposure in rats. 265 77

Short term angiotensin converting enzyme inhibition may induce a transient salt and water retention in patients with hypertension or heart failure. To verify the glomerular and tubular effects of short term converting enzyme inhibition, thirteen patients with mild to moderate essential hypertension (WHO I-II) were treated orally either with perindopril (4 mg o.d.) or captopril (25 mg b.i.d.) for one week. Both drugs reduced supine mean blood pressure significantly (p less than 0.01) (perindopril from 126 +/- 11 to 108 +/- 7 mmHg, mean +/- SD, and captopril from 132 +/- 12 to 121 +/- 16). Plasma volume (radio-iodinated albumin space) was unchanged while mean extracellular fluid volume (inulin space) increased although not significantly (from 5.05 +/- 1.32 l/sqm to 5.71 +/- 2.21 with perindopril and from 4.96 +/- 2.6 to 5.6 +/- 1.7 with captopril). Sodium clearance decreased (from 1.4 +/- 0.6 to 1.1 +/- 0.5 ml/min 1.73 sqm with perindopril, p less than 0.05, and from 0.97 +/- 0.44 to 0.88 +/- 0.51 with captopril, n.s.). In 9 patients (6 on captopril and 3 on perindopril) extra-cellular fluid volume increased simultaneously with reduction in glomerular filtration rate and in proximal tubule sodium re-absorption as well as an increase in distal tubule sodium reabsorption. In these patients the changes in proximal and distal tubule sodium reabsorption were significantly (p = 0.05) different from those of the patients with no extra-cellular fluid expansion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Volume of the extracellular liquid and renal function during short-term administration of angiotensin converting enzyme inhibitors in essential hypertension]. 267 Jun 57

The stop-flow technique was used to determine the site of entry of kininase II into tubular fluid in dogs. Stop-flow patterns were constructed for kininase II, p-aminohippurate, sodium, and potassium. The proximal tubule was localized by the peak of p-aminohippurate concentration and the distal tubule by the minimum sodium concentration. In the stop-flow pattern for kininase II, three peaks (a, b, and c) were observed. A main peak (a), located 2.25 +/- 0.45 ml distal to the p-aminohippurate peak (p less than 0.01) and 3.75 +/- 0.31 ml proximal to the minimum sodium concentration (p less than 0.001), was observed in all experiments. Peak c, located 2.6 +/- 0.4 ml (p less than 0.01) proximal to the p-aminohippurate peak, was observed in five dogs. Peak b appeared in five dogs and was always located 2.0 ml distal to the minimum sodium concentration. This peak was coincident with the potassium peak. Only two of eight experiments showed all three peaks. These results showed that the major kininase II entry into the tubular fluid is near the p-aminohippurate peak and that distal entry occurred in 63% of the dogs.
Hypertension 1988 Feb
PMID:Site of entry of kininase II into renal tubular fluid. 283 Nov 47

Free intracellular calcium was measured in renal proximal tubules obtained from spontaneously hypertensive rats (SHR) and from age-matched Wistar-Kyoto rats (WKY) ingesting a normal diet. Experiments were performed on renal proximal tubule suspensions using fura-2 to monitor cytosolic calcium. In 4-week-old rats, when systolic blood pressure was not significantly different between the two groups, renal proximal tubule cytosolic calcium was similar (143 +/- 28 and 144 +/- 15 nM, respectively). By the age of 5 weeks, cytosolic calcium increased significantly in both SHR and WKY (214 +/- 24 and 262 +/- 34 nM, respectively, p less than 0.05). Calcium, however, was not significantly different between the two groups, even though at this age blood pressure was higher in SHR than in WKY. As compared with values in 4-week-old rats, cytosolic calcium was also found increased in tubules from both SHR and WKY aged 10 to 12 weeks (261 +/- 42 and 279 +/- 30 nM, respectively) and 20 to 24 weeks (263 +/- 42 and 308 +/- 28 nM, respectively). However, no significant differences in cytosolic calcium were found between SHR and WKY even though at these ages systolic blood pressure increased markedly in the SHR. Moreover, regression analysis failed to reveal a correlation between cytosolic calcium and blood pressure when data from either group of rats of all ages studied were pooled. Exposure to ouabain (10(-3) M) to inhibit Na+,K+-adenosine triphosphatase and increase intracellular sodium had no significant effect on cytosolic calcium in tubules from either SHR or WKY (260 +/- 69 and 250 +/- 45 nM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1988 Oct
PMID:Free cytosolic calcium in renal proximal tubules from the spontaneously hypertensive rat. 284 68


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