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)

To study the hypotensive mechanism of the new oral converting-enzyme inhibitor, MK-421, we evaluated the antihypertensive effect of MK-421 in rats with hypertension induced by chronic administration of norepinephrine (NE) or vasopressin and measured urinary kallikrein and kinin excretions as indices of the renal kallikrein-kinin system. When 6 mg/kg/day of MK-421 was administered simultaneously with 1.8 mg/kg/day of NE, the systolic blood pressure of conscious rats rose on Day 1 to only 122.6 +/- 3.4 mm Hg compared with the rise to 146.3 +/- 1.6 mm Hg when NE alone was infused (p less than 0.001). Similarly, when the same dose of MK-421 was administered simultaneously with 7.2 U/kg/day of vasopressin, the systolic blood pressure of conscious rats rose on Day 1 to only 117.4 +/- 3.8 mm Hg compared with the rise to 141.6 +/- 3.4 mm Hg when vasopressin alone was infused (p less than 0.01). The antihypertensive effect of MK-421 was sustained for 6 days in rats infused with NE or vasopressin. Infusion of NE alone resulted in a small but significant increase in urinary kallikrein excretion and no change in urinary kinin excretion. The combined administration of NE with MK-421 induced additional increases in urinary kallikrein and kinin excretions. Vasopressin alone resulted in marked decreases in urinary kallikrein and kinin excretions. The combined administration of vasopressin with MK-421 induced no additional changes in urinary kallikrein and kinin excretion. These results indicate that the hypotensive effect of MK-421 may depend on a reduced sensitivity of the peripheral arteries to vasoconstrictor substances.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Antihypertensive effect of MK-421 in rats. Role of the renal kallikrein-kinin system. 632 17

To clarify the possible risk factors for the development of hypertension, we examined the influences of heredity and environment on blood pressure regulation and whether or not the physiological condition differed in high school students with different levels of blood pressure. A borderline hypertensive (BH) group, consisting of 75 male students with systolic blood pressure (SBP) consistently above 140 mmHg on two separate occasions, was compared to a normotensive (N) group of 84 male students with SBP below 130 mmHg. In the BH group, 43% of students had a family history of hypertension within two generations of relatives, while 18% had one in the N group (p less than 0.05). The BH group was characterized by a gain in weight, a slight increase in 24-hour urinary sodium excretion, a higher heart rate, elevated values of plasma renin and urinary aldosterone, and an elevated sodium concentration in erythrocytes. Nevertheless, urinary excretion of potassium and kallikrein did not differ between the two groups. In each group, students with familial hypertension had a significantly (p less than 0.05) lower 24-hour urinary kallikrein excretion than those without it. Although kallikrein excretion correlated fairly well with aldosterone excretion (r = 0.47, p less than 0.01) or creatinine clearance (r = 0.59, p less than 0.01) in the BH students without familial hypertension, no such correlations were found in those with familial hypertension. These results indicate that the abnormal relationships of aldosterone to kallikrein metabolism and of kallikrein to renal function control may be involved as hereditary factors in the development of hypertension.
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PMID:Environmental and physiological characteristics in adolescents genetically predisposed to hypertension. 633 71

The present study was performed to investigate the roles of renal kallikrein and prostaglandin (PG) E in the mechanism of the exaggerated fractional Na excretion in hypertensive patients with advanced renal disease by means of the determination of urinary excretion of kallikrein and PGE, and fractional Na excretion in 20 healthy volunteers and 41 patients with chronic glomerulonephritis (14 normotensive patients; 9 borderline hypertensive patients; 18 sustained hypertensive patients). Urinary excretion of kallikrein and PGE was significantly decreased in patients with sustained hypertension as compared with healthy volunteers, while not decreased in those with normotensive or borderline hypertensive patients. Four times higher values for the fractional Na excretion and four or five times higher values for the urinary excretion of PGE corrected for creatinine clearance, were found in patients with borderline or sustained hypertension. There was a significant positive correlation (r = 0.6777) between the two. These results suggest that PGE in the renal tubular compartment may be involved in the mechanism of the exaggerated fractional Na excretion in patients with advanced renal disease. The urinary excretion rate of kallikrein corrected by creatinine clearance was three times greater in patients with borderline hypertension, but no significantly increase in those with sustained hypertension compared with that in healthy volunteers. There was no significant correlation between the fractional Na excretion and urinary kallikrein excretion corrected for creatinine clearance.
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PMID:Renal kallikrein and PGE in the exaggerated fractional Na excretion in patients with chronic renal failure. 634 85

Urinary kallikrein excretion was studied in 34 patients with mild, normal-renin, essential hypertension without evidence of target organ damage and in 23 normotensive controls, using assays that measure both active (kininogenase activity) and total (active plus inactive) kallikrein. There was no significant difference in either active or total kallikrein excretion between the two groups. However, the ratio of active-to-total enzyme was decreased in the hypertensives (0.83 +/- 0.03 units/micrograms) compared to the normotensives (1.00 +/- 0.05 units/micrograms) (p less than 0.002). The active-to-total ratio was inversely related to sodium excretion in both groups, indicating that the proportion of active to inactive enzyme increased in response to reduced sodium intake. We conclude that, although absolute excretion of active and total kallikrein is not decreased, enzyme activity per microgram of total kallikrein excreted is reduced in mild, normal-renin essential hypertension. This abnormality may be due to a defective enzyme, or to a reduced excretion of active relative to inactive kallikrein. The latter could result from the presence of a urinary kallikrein inhibitor or to reduced activation of a proenzyme.
Hypertension
PMID:Reduced ratio of active-to-total urinary kallikrein in essential hypertension. 634 66

Urinary kallikrein excretion was measured in 46 young patients with borderline hypertension and 28 age-matched normotensive subjects. Hypertensives excreted greater amounts of kallikrein than normotensives (2.31 +/- 0.20 units/day vs. 1.56 +/- 0.17 units/day, p less than 0.01). Plasma renin activity (PRA) was also increased in hypertensives. Moreover, urinary kallikrein was increased in hypertensive patients with high PRA (PRA greater than or equal to mean + 1SEM in normotensives; n = 25) as compared to patients with normal PRA (PRA less than mean + 1SEM; n = 21). In hypertensives with normal PRA, urinary aldosterone correlated to urinary kallikrein (r = 0.478, p less than 0.05), as in normotensives (r = 0.451, p less than 0.02). But, no correlation was found in patients with high PRA. Therefore, the results of the present study do not confirm the hypothesis that the deficiency of the kallikrein-kinin system is the primary cause of hypertension. In hypertensives with high PRA, there may be abnormality of the interaction between the renin-angiotensin-aldosterone system and the kallikrein-kinin system, whereas it may be normal in hypertensives with normal PRA as well as normotensives.
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PMID:Increased urinary kallikrein excretion in young borderline hypertensive patients. 634 68

The effect of the potassium-sparing diuretic, amiloride, was studied in conscious rabbits bearing chronic indwelling cannulas to assess whether its reported in vitro kallikrein-inhibiting activity may produce a suppressive effect on furosemide-induced renin secretion similar to that previously demonstrated with another kallikrein inhibitor, aprotinin. Furosemide elicited a rapid and persistent rise in plasma renin activity (PRA), but pretreatment of the same rabbits with a 15-minute intravenous infusion of amiloride, which amounted to 1 mg/kg and commenced at 30 minutes before furosemide, completely prevented this rise. Amiloride also prevented furosemide-induced kaliuresis without an attenuation of the diuretic or natriuretic response and did not alter plasma potassium concentration in the absence of any change in external potassium balance, indicating that suppression of the PRA response is due neither to prevention of extracellular fluid volume contraction nor to the known suppressive effect of hyperkalemia. Mean arterial pressure tended to fall slightly but not significantly with or without amiloride pretreatment. On the basis of these findings and those of our antecedent study with aprotinin, we conclude that the striking similarity between the suppressive effects of two dissimilar inhibitors of kallikrein on pharmacologically evoked renin secretion is consistent with the hypothesis that renal kallikrein participates in the mechanism of renin secretion in vivo.
Hypertension
PMID:Inhibition of furosemide-induced increases in plasma renin activity by amiloride. 635 81

Urinary excretion of kallikrein (UKal), sodium, potassium, protein, and creatinine, as well as the kidney content of kallikrein and renin, was studied in spontaneously hypertensive FH/Wjd (FH) male and female rats and in age- and sex-matched normal Wistar rats. With the exception of 1-month-old rats UKal excretion was significantly lower in FH rats than in Wistar rats. FH females also excreted less UKal than Wistar females. No UKal inhibitor or increased degradation of this enzyme in the urine of FH rats was detected. There was no difference in creatinine clearance, blood urea nitrogen, or serum electrolytes, and calcium between 5-month-old FH and Wistar males. Wistar rat kidneys contained about twice as much kallikrein as FH rat kidneys. From the age of 2 months FH males excreted more sodium, as well as urine, than all other groups. No differences in potassium excretion were observed. Only FH males, 4 months and older, developed proteinuria. FH males and females became hypertensive at the ages of 2 and 4.5 months, respectively. Plasma renin activity, as well as renal renin activity, was significantly lower in FH than in Wistar males. In conclusion, the decrease in UKal activity which precedes the onset of hypertension suggests that the abnormality in the renal kallikrein system may be involved in the pathogenesis of hypertension in FH rats.
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PMID:Urinary and renal kallikrein in hypertensive fawn-hooded (FH/Wjd) rats. 636 17

A 47-year-old woman with normotensive primary aldosteronism is reported. In this case, hypopotassemia was found, but the patient's blood pressure was within the normal range. Her condition was diagnosed as primary aldosteronism without hypertension, which is very rare, based on an increased level of plasma aldosterone concentration, low plasma renin activity, and a typical finding of aldosterone-producing adenoma by adrenal scintigraphy. In the present case, similar values for urinary volume, renal function, plasma aldosterone concentration, plasma renin activity, plasma volume, total exchangeable sodium, urinary kallikrein excretion and a similar weight of the resected adenoma, but a shorter duration between the onset of symptom and hospital admission were observed as compared with those in 13 previously experienced cases of primary aldosteronism with hypertension. Thus, a shorter duration of primary aldosteronism appears to be an important factor in explaining the mechanism of normotension. However, we were unable to reach a definite conclusion and this is only a hypothesis. Further investigation will be required to clarify the mechanism of normotension in primary aldosteronism.
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PMID:A case of normotensive primary aldosteronism--comparison with 13 previously experienced cases with hypertension. 637 8

Dahl salt-sensitive (S) rats which are susceptible to hypertension have lower urinary kallikrein excretion than salt-resistant (R) rats which are not susceptible. Some physicochemical characteristics of partially purified urinary kallikrein were compared between the S and R strains. The isoelectric focusing pattern of S kallikrein was shifted so that a higher proportion of enzyme was present in isoelectric forms that had higher pI values compared to the pattern for R kallikrein. This strain difference was unique to urinary kallikrein; it was not seen in kallikrein extracted from salivary glands. The isoelectric focusing pattern for R urinary kallikrein could be converted to an S-type pattern by treatment with neuraminidase, which suggests that the differing isoelectric focusing patterns arose from differences in the sialic acid content of the kallikrein. The S kallikrein was slightly more heat-labile than R kallikrein, which was also compatible with the lower sialic acid content of the S enzyme. Tests involving the active site of the enzyme (Km values, pH curves, and heat of activation) were identical for the S and R strains. It was concluded that the structural differences observed in urinary kallikrein between S and R strains were compatible with strain-specific posttranslational processing of the enzyme.
Hypertension
PMID:Isoelectric focusing patterns of urinary kallikrein in Dahl salt-hypertension susceptible and resistant rats. 637 89

In vitro studies were performed to investigate the direct effects of the cyclooxygenase inhibitors (COI), meclofenamate, imidazol, acetylsalicylic acid (ASA), indomethacin, and acetaminophen on the plasma kallikrein system and on urinary kallikrein excretion. Biological (guinea pig ileum) and colorimetric (synthetic substrate) methods were used. Results showed that all COIs except ASA affected both the activation of pre-kallikrein in plasma and the direct activity of plasma kallikrein, but none of the COIs tested was able to alter the urinary kallikrein excretion. Additionally, in Wistar rats we studied the effects of chronic administration of ASA, meclofenamate, and indomethacin on the plasma kallikrein system and urinary kallikrein excretion. In contrast to the in vitro studies, administration of these COIs reduced the amount of total 24-hour urinary kallikrein excretion. Moreover, the pre-plasma kallikrein and total plasma kallikrein levels were diminished in all experimental groups. However, only ASA and meclofenamate increased the free-plasma kallikrein levels despite the fact the three COIs used reduced the high molecular weight kininogen. Thus, in vitro data suggest an important and direct effect of meclofenamate, imidazol, indomethacin, and acetaminophen on the plasma kallikrein system, without any effect on urinary secretion. ASA was the only COI that showed no direct effect in these experiments. Chronic COI administration in Wistar rats suggests that ASA, meclofenamate, and indomethacin affect both the plasma kallikrein-kinin system and kallikrein excretion. When these drugs are used to evaluate the interactions between prostaglandins and the kallikrein-kinin system, their possible effects through both mechanisms, directly or via prostaglandin inhibition, should be considered.
Hypertension
PMID:Effects of cyclooxygenase inhibitors on plasma and urinary kallikrein. 641 49


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