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)

Inhibition of angiotensin converting enzyme by MK 421 (6 mg/kg/day ip) induced a significant increase in urinary kinin excretion in norepinephrine-infused rats (1.8 mg/kg/day ip), whereas it had no effect on urinary prostaglandin E2 excretion. In contrast, MK 421 did not induced any significant changes in urinary kinin and prostaglandin E2 excretion in vasopressin-infused rats (7.2 U/kg/day ip). The simultaneous administration of indomethacin (10 mg/kg/day sc), OKY 046 (12 mg/kg/day sc) or aprotinin (100,000 units/kg/day sc) did not affect the antihypertensive effect of MK 421 in rats made hypertensive by chronic infusion of norepinephrine or vasopressin. The present results suggest that the hypotensive effect of MK 421 may depend on a reduced sensitivity of the vasculature to vasoconstrictor substances. In addition, it is also suggested that neither the prostaglandin-thromboxane or kallikrein-kinin systems are essential for the antihypertensive effect of MK 421 in these models of hypertension.
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PMID:No evidence on significant roles of the prostaglandin-thromboxane and kallikrein-kinin system in the antihypertensive effect of MK 421 in rats made hypertensive by norepinephrine or vasopressin. 244 Jun 25

To assess possible roles of the renal kallikrein-kinin system in the development of spontaneous hypertension, we determined daily excretion of urinary total and active kallikrein in 6-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats for up to 2 weeks. We also evaluated the effect of aprotinin, a reversible inhibitor of kallikrein and other serine proteases, on the development of hypertension in the 6-week-old SHR on ordinary intakes of sodium or on sodium loading with 1% NaCl for up to 2 weeks. Active kallikrein was determined by its kininogenase activity, and the generated kinins were radio-immunologically measured. Total kallikrein was also determined by measuring kininogenase activity after inactive kallikrein had been activated with trypsin (200 micrograms/ml). Urinary active kallikrein excretion was significantly reduced in 7-week-old SHR (1.5 +/- 0.2 microgram/day compared to 2.8 +/- 0.3 micrograms/day in WKY, P less than 0.05) and in 8-week-old SHR (1.6 +/- 0.2 microgram/day compared to 3.2 +/- 0.4 micrograms/day in WKY, P less than 0.01). Urinary total kallikrein excretion was also reduced in the 7- and 8-week-old SHR whereas the ratio of active to total kallikrein did not change. In addition, renal contents of total and active kallikrein were significantly lower in the 8-week-old SHR than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal kallikrein activity in spontaneously hypertensive rats. 244 68

The main vasodepressor hormone systems are the kallikrein-kinin systems and the vascular prostacyclin. Kallikreins release kinins which are the biological active compounds of the kallikrein-kinin systems. Kinins are one of the most potent vasodilators reducing systemic blood pressure by diminution of vascular resistance. The reduction in blood pressure is strongly dose related. Prostacyclin develops similar effects on blood pressure as kinins. There is a close relationship between kinins and prostacyclin since kinins stimulate prostacyclin synthesis very effectively. In arterial hypertension there is a lack in kallikrein-kinin and prostacyclin activity. This could also be shown under experimental conditions in spontaneously hypertensive and in Dahl salt-sensitive rats. In clinical studies these experimental results were confirmed in primary hypertension. The blood pressure response to exogenous vasodepressor hormones is increased in hypertensives suffering from reduced endogenous vasodilator activity. In the knowledge of reduced vasodilator activities in primary hypertension the stimulation of kinins by prostacyclin will be of major interest in the management of primary hypertension. In the last years some drugs have been investigated with regard to their kinin prostacyclin stimulating effect, but only angiotensin converting enzyme inhibitors, linolenic acid and cicletanin seemed to induce therapeutic prostacyclin stimulation. However, it remains unclear whether these drugs develop their blood pressure lowering effect by stimulation of the discussed vasodilators or by some other effect.
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PMID:Role of kinins and prostacyclin in blood pressure regulation. 251 56

We performed an epidemiological study on the atrial natriuretic factor pattern in a young population. Subjects were recruited in the Ospedale Militare Principale of Rome among young men liable to conscription, whose hospitalization was due either to essential hypertension or to other pathologies (not influencing our study, such as headache etc.). The recruitment lead to the formation of three different groups: normotensives, normotensives with family history of hypertension (mother and/or father) and hypertensives. On the morning of the study (after 7 days of pharmacological wash-out, under a diet containing 120 mEq of Na+/die), blood samples were taken. Plasma atrial natriuretic factor, renin activity and aldosterone were assayed by RIA. Digoxin-like immunoreactive substance was assayed by a solid-phase radioimmunoassay, following the extraction of plasma. Serum creatinine, sodium, potassium and urinary sodium and potassium (24 h before the study) were assayed by standard methods. Urinary kallikrein was assayed by chromogenic substrate S-2266. So far, we have studied 60 subjects (26 hypertensives, 21 normotensives and 13 normotensives with family history) and we wish to discuss in this article the preliminary results concerning the atrial natriuretic factor and its relationship with renin activity, aldosterone and blood pressure. Our results show that the mean plasma levels of atrial natriuretic factor in the hypertensive group were higher, although not significantly, than those of the other two groups and that the normotensives with family history had slightly higher levels as compared to normotensives (Delta % = + 7.4).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Atrial natriuretic factor: an epidemiological study. Preliminary results]. 252 19

In order to further clarify the role of renal kallikrein-kinin (K-K) system in primary aldosteronism (PA), daily urinary excretions of renal K-K system components including kallikrein (KAL), kinin (KIN), total kininase (K-ase), K-ase I, K-ase II and neutral endopeptidase (NEP) were measured in PA and normotensives (NT). In this study, a new method for the simultaneous determination of human urinary K-ase I, II and NEP was established and employed. The daily excretions of KAL was significantly higher in PA than that in NT, while no difference was found in KIN between PA and NT. On the other hand, total K-ase in PA (897 +/- 258 micrograms/min/day) was significantly higher than that in NT (209 +/- 6). NEP was also significantly higher in PA (262 +/- 22 micrograms/min/day) than that in NT (127 +/- 6), whereas there were no differences in K-ase I and K-ase II between PA and NT. The relative contributions of K-ase I, II and NEP to total K-ase in NT were 14, 27 and 59%, while those in PA were 12, 17 and 36%, respectively. As a result, these three K-ase contributed only 64% to the total K-ase in PA. These findings suggested that 1) NEP may play a major role in the catabolism of renal KIN in human, 2) NEP is accelerated in PA, 3) unknown K-ase, different from K-ase I, II or NEP, may exist in PA, and 4) accelerated renal K-ase activity may play some role on the disorder of renal water-sodium metabolism and high blood pressure in PA.
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PMID:Renal kininases in primary aldosteronism. 255 6

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

We have explored the role of kallikrein-kinin system in essential hypertension using spontaneously hypertensive rats (SHR) as an animal model. A rat tissue kallikrein complementary (c) DNA (RSK 1105) was used as a probe in Southern blot hybridization to detect restriction fragment length polymorphisms (RFLPs) in SHR. Using 23 different restriction endonucleases, we have identified five RFLPs involving alterations in restriction fragment lengths for the restriction enzymes Bgl II, Dra I, Nde I, Sph I, and Bcl I. Three of the enzymes, Nde I, Sph I, and Bgl II, generate multiple polymorphic fragments. We have further mapped these RFLPs with two additional probes, both from the rat renal kallikrein gene RSKG 7. The 5' probe, consisting of sequences approximately 2000 base pair (bp) 5' of the first exon, recognizes RFLPs in DNA digested with Bcl I and Sph I. The 3' probe, approximately 4400 bp away from the fifth exon, recognizes polymorphic fragments in DNA digested with Bcl I, Dra I and Nde I. These findings indicate possible differences in tissue kallikrein genes or their regulatory regions in SHR that could contribute to the pathogenesis of hypertension in this animal model.
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PMID:Restriction fragment length polymorphisms mapped in spontaneously hypertensive rats using kallikrein probes. 257 14

Aprotinin, the serine protease inhibitor that also inhibits glandular (urinary) kallikrein, or vehicle was infused into the aorta above the renal arteries of anesthetized pigs. Renal hemodynamic and functional parameters were followed over time and during hemorrhagic hypotension. Both renal cortical blood flow and glomerular filtration rate were maintained in vehicle-treated animals at mean arterial pressures as low as 70 mm Hg. As long as renal cortical blood flow and glomerular filtration rate were maintained during the progressive hypotension, urinary excretion rate of kallikrein (as defined by kinin-generating activity) was increased. In contrast, all aprotinin-treated animals had a decreased excretion rate, and the renal cortical blood flow declined with the mean arterial pressure during hemorrhage. The pattern of glomerular filtration rate and plasma renin activity was comparable in both aprotinin-treated and vehicle-treated hemorrhaged animals. Our findings suggest that the endogenous renal kallikrein-kinin system is required for functional renal vasodilatation to maintain renal cortical blood flow during hemorrhage and is therefore directly or indirectly responsible for adjustment of preglomerular resistance.
Hypertension
PMID:Effect of the protease inhibitor aprotinin on renal hemodynamics in the pig. 257 4

Numerous studies have suggested that a functional relationship may exist between the kallikrein-kinin and the renin-angiotensin systems within the kidney. We investigated the effects of glandular kallikrein on renin release by using an in vitro preparation of isolated rat glomeruli with their attendant arterioles. The effect of kallikrein was studied in the presence or absence of 0.1% bovine serum albumin (BSA) in Krebs superfusion fluid. We also studied the effect of inactivating kallikrein by treatment with phenylmethylsulfonyl fluoride or by inhibiting it with aprotinin. In the absence of BSA, kallikrein caused a 12-fold increase in renin release, from 5.1 +/- 1.2 ng angiotensin I (ANG I)/min to 66.0 +/- 2.27 ng ANG I/min (p less than 0.025). In the presence of BSA, renin release increased twofold, from 13.0 +/- 1.8 ng ANG I/min to 24.3 +/- 4.8 ng ANG I/min (p less than 0.025). The basal level of renin measured when the glomeruli were superfused with BSA-Krebs was two to three times greater than when they were superfused with Krebs alone (p less than 0.001). This finding suggests that media protein inhibited renin loss during either the superfusion or storage of renin samples. Neither phenylmethylsulfonyl fluoride-inactivated nor aprotinin-inhibited kallikrein stimulated renin release. We propose that kallikrein can stimulate renin release in isolated glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Effect of glandular kallikrein on renin release in isolated rat glomeruli. 257 3

The effects of dietary K (food and tap water both containing 1% KCl) on blood pressure and renal prostaglandin-kallikrein-kinin system were investigated in Wistar rats made hypertensive by constriction of left renal artery. Dietary K attenuated the development of hypertension and increased urine volume accompanied by increased excretion of K, but by uninfluenced excretion of Na. Dietary K also increased the urinary excretion of kallikrein, PGE2 and aldosterone in Goldblatt hypertensive rats. There was no significant difference in the values of plasma Na between the two groups with and without dietary K. These results suggest that dietary K may attenuate the development of hypertension, increase urine volume via the mechanism of enhancing production of renal PGE2 and kallikrein in hypertensive rats.
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PMID:[Effects of dietary K on blood pressure, prostaglandin, and kallikrein in renovascular hypertensive rats]. 261 29


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