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)

We determined kinin-generating activity (kininogenase) in the thoracic aorta of spontaneously hypertensive rats (SHRs) at age 5 and 15 weeks and in appropriately age-matched Wistar-Kyoto (WKY) rats. Aorta homogenates were incubated with partially purified dog kininogen, and the resulting kinins were extracted with ethanol. The kinins were determined by a sensitive kinin radioimmunoassay (RIA). Kininogenase activity was expressed as mean +/- SEM, picogram kinin generated/mg x protein/h. Active kininogenase in SHR was approximately one-third in 5-week-old and about one-fifth in 15-week-old rats when compared with their normotensive controls. Total kininogenase activity in SHRs was approximately 80% and 58% of the normotensive controls at ages 5 weeks and 15 weeks, respectively. Active enzyme was 14% of the total in 5-week-old SHRs, and it was only 5% of the total in 15-week-old SHRs. It seems unlikely that the changes in kininogenase are secondary to hypertension because blood pressor is only marginally elevated at 5 weeks according to the literature. We hypothesize that genetic hypertensive rats may suffer from an inherent deficiency in the kininogenase activity of the vascular wall. The deficiency may also be in the mechanism of activation of precursor enzyme.
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PMID:Kininogenase of the aortic wall in spontaneously hypertensive rats. 128 21

To clarify the relationship between kallikrein-kinin and renin-angiotensin systems, glandular kallikrein, renin and angiotensin converting enzyme in the submandibular gland, the kidney and plasma were investigated in streptozotocin diabetic and spontaneously hypertensive rats. Kallikrein content in the submandibular gland, the kidney and plasma of diabetic rats was found to be decreased compared with nondiabetic controls. Renin activity in diabetic rats was also reduced in the submandibular gland, but the activity showed no significant changes in the kidney and plasma. The activity of angiotensin converting enzyme (ACE) in plasma significantly increased in diabetic rats. On the other hand, kallikrein content in hypertensive rats was depressed in the kidney, while the content was unchanged in the submandibular gland and plasma. Renin activity in hypertensive rats was found to be higher than that of normotensive rats in the submandibular gland, but the activity showed no remarkable changes in the kidney and plasma. ACE activity in plasma markedly decreased in hypertensive rats in contrast to diabetic rats. In hypertensive-diabetic rats, changes in the levels of these enzymes in tested materials were similar to those of diabetic rats. From these results it is reasonable to assume that (1) reduced kallikrein generation and elevated ACE activity may induce impaired kinin formation and contribute to the development of diabetes mellitus apart from the presence of hypertension and (2) low kallikrein content in the kidney could cause hypertension.
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PMID:Glandular kallikrein, renin and angiotensin converting enzyme of diabetic and hypertensive rats. 255 14

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

The intrarenal kallikrein-kinin system was studied during the acute phase of renovascular hypertension induced by renal artery constriction and during teprotide inhibition of kininase II in the dog. Kallikrein-like activity measured by both kininogenase and esterolytic assays, was increased during renal artery constriction (p less than 0.5) and (p less than 0.01). The administration of teprotide resulted in a further increase of renal cortical kallikrein-like activity and inhibited kininase II activity (p less than 0.01). Following the inhibition of kininase II, the plasma concentration of kininogen was also significantly decreased (p less than 0.01). These results suggest that kininase II inhibition may increase levels of intrarenal and plasma kinins and that decreased degradation of kinin peptides may contribute significantly to the acute hypertensive effect of teprotide.
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PMID:Intrarenal kallikrein-kinin activity in acute renovascular hypertension in dogs. 285 35

The activity of basal 24-hour urinary kallikrein activity (UKA), prostaglandin E2 (U. PGE2) and thromboxane B2 (U. TxB2) and their relationship to natriuresis (U. Sodium), urinary aldosterone (U. Aldosterone) and plasma renin activity (in supine position: PRA1; in standing position: PRA2) were evaluated in 20 patients with early-moderate hemodynamically defined (first pass and gate blood pool radionuclide angiocardiography) essential hypertension (H) and in 13 age-matched normotensive patients (N). In basal conditions, UKA and PRA2 were significantly reduced (p less than 0.005 and p less than 0.05, respectively) in H compared with N. However, no differences between N and H were found for U. TxB2, U. PGE2, U. Aldosterone, U. Sodium, and PRA1. All parameters were also evaluated both in H and N before and after the administration of furosemide (40 mg i.v.). In H, but not in N, furosemide induced an increase of UKA (p less than 0.05), U. TxB2 (p less than 0.05) and U. Sodium (p less than 0.001). In both H and N furosemide caused a significant rise of PRA1 (p less than 0.001 in H and p less than 0.01 in N) and PRA2 (p less than 0.001 in H and p less than 0.05 in N). In H a significant correlation was found between percent increases of U. Sodium and U. Kallikrein (r = 0.54, p less than 0.01) and between percent differences of PGE2 and TxB2 (r = 0.59, p less than 0.01). It is proposed that reduction of basal UKA may be an early evidence of the first stages of hypertension, i.e., in absence of renal and cardiovascular alteration. The finding is not accompanied by significant changes in urinary excretion of arachidonic acid metabolites and aldosterone. Finally, any relation between UKA values and systemic hemodynamics is lacking.
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PMID:Acute effect of furosemide on renal kallikrein and prostaglandin systems in mild to moderate essential hypertension. 354 80

Kallikrein and kininase activities were determined in urine of 58 hospitalized pregnant patients: 15 with E.P.H. gestosis, 10 with chronic hypertension, 18 with non proteinuric pregnancy induced hypertension, 15 with no hemodynamic disease as controls. All our cases with hypertension were treated with alpha-methyl-dopa. A significant increase in urinary kininase activity was shown by only E.P.H. gestosis group vs. controls. In the same group we found a significant decrease in urinary kallikrein activity vs. controls, in contrast with the results obtained previously, perhaps because of the different measuring method. The kininase/kallikrein ratio, theoretically indicative of kinins activity, increased significantly only in the E.P.H. gestosis group.
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PMID:Urinary kallikrein and kininase activity in normal and complicated by hypertension pregnancy. 381 2

Basolateral membrane (BLM) enriched fraction was isolated from homogenized rat kidney cortex by differential centrifugation. We also obtained a fraction enriched in plasma membrane (PM). The morphology of the isolated BLM fragments was studied by transmission and freeze fracture electron microscopy. The relative specific activity of Na+-K+-ATPase was enriched 7-fold, while that of marker enzymes for PM, endoplasmic reticulum, and lysosomes was lower than in the crude homogenate. There was a 10-fold difference in the ratios of activities of Na+-k+-ATPase to Mg2+-ATPase in the BLM and in the PM enriched fractions. Kallikrein activity was determined with S-2266 substrate and by radioimmunoassay of kinin released. It was low in the BLM fraction prior to adding detergent, but Triton X-100 increased the activity 12 to 16-fold. Both free trypsin and Sepharose 4B-bound insoluble trypsin increased kallikrein activity 2- to 3-fold in both the membrane-bound and soluble fractions, probably by activating a prekallikrein. The results were interpreted that the kallikrein studied originated from the distal tubular BLM.
Hypertension
PMID:Kallikrein and prekallikrein on the basolateral membrane of rat kidney tubules. 627 73

Renal tissue kallikrein and proteins were measured in two kidney-one clip Goldblatt hypertensive rats both in the stenotic and the controlateral kidney and in sham operated rats at either 1 or 2 weeks after clipping. Activity was assessed by the amidolytic activity and by the kininogenase activity. Kallikrein in normotensive controls was 97.4 +/- 13 ng of bradykinin min-1 mg-1 of protein at week 1 and increased up to 116 +/- 18. Kallikrein in the GH rats was 83 +/- 12 in the stenotic kidney and 85,6 +/- 14 in the controlateral one at week 1, these values remained unchanged at week 2. As a consequence renal tissue kallikrein became significantly lower in the GH rats only at week 2 when compared to controls both the clipped and unclipped kidney showed the same magnitude decrease. Protein concentration remained at a steady level through out the 2 weeks of study. The results suggest that the lower renal kallikrein activity secondary to hypertension found in GH rats result from a decreased activation of prekallikrein in both kidney.
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PMID:[Changes in the activity of renal intracortical kallikrein during induction of Goldblatt arterial hypertension of the 2 kidney--1 clip type in the rat]. 644 40

The plasma renin activity (PRA), plasma volume (PV), urinary excretion of Kallikrein (UK) and PGE2, PGF2 alpha, 6-keto PGF1 alpha and TXB2 were measured in 24 ambulant patients without treatment on normal sodium diets with pregnancy-induced hypertension (HT) (diastolic BP greater than or equal to 90 mmHg, appearing after 20 weeks' pregnancy and absent 2 months after delivery). The UK was measured by an esterase technique, prostaglandins by radioimmunological assay and PV by dye dilution (Evans blue). Two subgroups of patients were identified according to the evolution of their blood pressure at rest at home; the first (7 patients) with labile HT, and the second (14 patients) with permanent HT. The PRA was significantly lower (p less than 0,001) in patients with permanent compared to labile hypertension (4,7 +/- 0,3 compared to 12,2 +/- 0,8 ng/ml/h) and compared to a control group of normotensive pregnant women (6,5 +/- 0,5). The PV, expressed as a percentage of the theoretical volume with respect to the stage of pregnancy and body surface area was low in both groups. In permanent HT: 1) there was no correlation between PV and PRA, 2) a positive correlation between UK and urinary 6-keto PGF1 alpha (r = 0,62; p less than 0,001) and PGE2 (r = -0,51, p less than 0,05). Discriminative linear analysis showed that urinary 6-keto PGF1 alpha was mainly related to PRA and to a lesser degree to UK.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Renin-angiotensin-aldosterone system, blood volume, serum uric acid and urinary excretion of prostaglandins and kallikrein in the arterial hypertension induced by pregnancy]. 644 41

In male spontaneously hypertensive rats (SHRSP) of the stroke prone strain (Okamoto) and in normotensive Wistar-Kyoto rats (WKY) urinary kallikrein excretion was investigated at different age and at drug-induced diuresis. In rats of both strains from 7th till 19th week of age urinary kallikrein excretion increased with age. In SHRSP of 7th till 11th week of age kallikrein excretion was higher than in WKY rats, while it was lower in the 48-week-old SHRSP. No correlation was found between urinary kallikrein excretion and systolic blood pressure. In SHRSP and WKY rats a similar daily rhythm of kallikrein excretion in urine was found being high in the early morning and low in the afternoon. Kallikrein excretion correlated significantly with urine volume. The loop diuretic bumetanide (4 and 40 mg/kg) induced diuresis and natriuresis in both strains, however more marked in the WKY rats than in the SHRSP. Urinary kallikrein excretion, however, showed in both strains the same biphasic course with a short lasting increase and a secondary decrease. Thus, in the average urinary kallikrein excretion was not effected by the drug. Prolonged treatment with furosemide over 5 days (125 mg/kg) resulted in an increase in kallikrein excretion in urine, more pronounced in the WKY rats than in the SHRSP. The observed results suggest that renal kallikrein-kinin system is not involved in the development of spontaneous hypertension as a pathogenetic factor, but rather is influenced by other factors like hormone interactions, i.e. mineralocorticoids and catecholamines, as well as renal function and acute changes in urine flow.
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PMID:The renal kallikrein-kinin system in spontaneously hypertensive rats. 657 82


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