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

Changes in auditory brain-stem responses (BER's) and somatosensory evoked responses (SER's) were investigated to correlate mass volume, intracranial pressure, and neurological dysfunction in mass-induced intracranial hypertension in cats. As the intracranial pressure was raised by expansion of a supratentorial balloon, the late components of the SER's were suppressed first, followed by the early components of the SER's, then Wave V and Wave IV of the BER's, in that order. This suggests that the nonspecific reticular projections are most vulnerable to compression ischemia, and the specific somatosensory pathways are the next most vulnerable. Neural activity of the auditory pathways in the upper brain stem was also gradually suppressed, but less so than that of the somatosensory pathways. After complete transtentorial herniation, in spite of immediate mass evacuation, the function of the somatosensory pathways was greatly impaired, often irreversibly. The neural activity of the auditory pathways in the upper brain stem revealed progressive recovery during a 3-hour period. The measurements of BER Wave V is thought to be useful in predicting transtentorial herniation.
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PMID:Acute intracranial hypertension and auditory brain-stem responses. Part 1: Changes in the aduitory brain-stem and somatosensory evoked responses in intracranial hypertension in cats. 50 7

An investigation was carried out to ascertain whether erythro- and threo-alpha-methyl-dihydroxy-phenyl-serine were able of depleting cerebral and peripheral norepinephrine (NE) through their metabolization to alpha-mNE. The results show that the alpha-methyl-aminoacids were decarboxylated only at the periphery and that the threo-form caused depletion in cardiac NE. In any case, both isomers were unable to cross the blood-brain barrier leaving the cerebral NE unaffected. Consequently the use of alpha-mDOPS as alternative tool to alpha-mDOPA in the therapy for hypertension seems unlikely to occur. The results also provide evidence for differences in the pharmacokinetics of the two isomers.
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PMID:Lack of hypotensive and brain catecholamine depleting effects by erythro- and threo-alpha-methyl DOPS. 58 13

The 130 kDa atrial natriuretic factor receptor (ANF-R1) purified from bovine adrenal zona glomerulosa is phosphorylated in vitro by serine/threonine protein kinases such as cAMP-, cGMP-dependent and protein kinase C. This phosphorylation is independent of the presence of ANF (99-126) and there is no detectable intrinsic kinase activity associated with the ANF-R1 receptor or with its activated form. In bovine adrenal zona glomerulosa cells, TPA (phorbol ester) induces a marked inhibition of the ANF-stimulated cGMP accumulation as well as of the membrane ANF-sensitive guanylate cyclase catalytic activity without any change in the binding capacity or affinity for 125I-ANF. However, we have demonstrated a significant 32P incorporation in the ANF-R1 receptor of the TPA-treated cells. The effect of TPA on the zona glomerulosa ANF-R1 receptors was abolished by calphostin C, a specific protein kinase C inhibitor. Altered ANF actions due to blunted response of guanylate cyclase to ANF could be a consequence of the ANF receptor phosphorylation by excessive activity of protein kinase C and might be involved in the pathogenesis of hypertension.
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PMID:Phosphorylation of atrial natriuretic factor R1 receptor by serine/threonine protein kinases: evidences for receptor regulation. 128 Mar 21

The mature neutrophils in the circulation contain, besides the different proteases known for a long time, a recently discovered proteolytically inactive elastase homologue (HBP/CAP37/azurocidin). This homologue, which we have named HBP due to its strong affinity to heparin, is a chemoattractant for monocytes and has been shown to induce reversible detachment and contraction when added to monolayers of endothelial cells or fibroblasts. HBP may therefore play a pivotal role in leukocyte migration in response to inflammation. In this report a comparison of CH3O-Suc-Ala-Ala-Pro-Val-CH2Cl-inhibited elastase with HBP, its naturally occurring homologue selectively mutated in active serine and histidine, reveals that homotypic aggregation of monocytes and contraction of fibroblasts is specific for HBP. HBP induces thrombospondin secretion from monocytes four times as efficiently as the inhibited elastase, and the same molecule was found unable to compete for a specific saturable binding of HBP to monocytes with an apparent KD of 3 x 10(-8)M.
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PMID:Comparison of the effects of methoxysuccinyl-Ala-Ala-Pro-Val-chloromethyl ketone-inhibited neutrophil elastase with the effects of its naturally occurring mutationally inactivated homologue (HBP) on fibroblasts and monocytes in vitro. 149 75

This study was undertaken in order to investigate the newly discovered spontaneously hypertensive rat (SHR)-specific restriction fragment length polymorphism (RFLP) at the genomic locus of (poly)phosphoinositide-specific phospholipase C (PLC)-delta at a DNA sequence level. Our aim was to clone the PLC-delta complimentary DNA (cDNA) from SHR and analyse the genomic DNA obtained from two hypertensive rat strains such as SHR and its stroke-prone substrain (SHR-SP) and three normotensive rat strains such as Sprague-Dawley, Donryu and Wistar-Kyoto (WKY) by preparing an aortic cDNA library of SHR, hybridization cloning of PLC-delta cDNA and an analysis of the genomic DNA by polymerase chain reaction. By digesting with restriction enzyme XhoI, we discovered an RFLP band displaying only in SHR and SHR-SP, not in Sprague-Dawley, Donryu and WKY rats. DNA sequencing of PLC-delta cDNA cloned from an aortic cDNA library of SHR revealed a total of three SHR-specific point mutations, two of which resulted in amino acid substitutions. The first point mutation (A to T) was detected at the XhoI site, changing a threonine(ACG) to a serine(TCG), and the second point mutation (A to G) was discovered in the vicinity of the first one, changing an isoleucine(ATA) to a methionine(ATG). This is the first demonstration of the mutations in the SHR genome changing amino acid sequences. These amino acid substitutions, situated in the putative catalytic X domain of PLC-delta, may be the major cause of the augmented PLC activity observed in the SHR, possibly leading to hypertension-related phenonemoma such as abnormal calcium homeostasis and increased intracellular calcium ion concentrations.
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PMID:Phospholipase C-delta gene of the spontaneously hypertensive rat harbors point mutations causing amino acid substitutions in a catalytic domain. 168 14

The circulatory effects of intracisternal injections of amino acids were investigated in conscious normotensive control rats (NCR) and in two-kidney, one-clip renovascular hypertensive rats (RHR). Arterial pressure was measured with an indwelling catheter connected to a pressure transducer. Heart rate was counted from the arterial pulse. The intracisternal injection of glycine, gamma-aminobutyric acid (GABA), taurine, serine, alanine, and sarcosine decreased blood pressure by an average of 16-30 mmHg in NCR and by an average of 32-55 mmHg in RHR. Both absolute and percent changes of depressor effects by GABA, taurine, serine, and alanine were larger in RHR than in NCR. All these amino acids also showed similar bradycardiac effects in both NCR and RHR, when compared in absolute values. The percent change of bradycardia induced by taurine and sarcosine was larger in RHR than in NCR. However, the degree of bradycardia by serine was larger in NCR than in RHR. These results suggest that serine, alanine, and sarcosine in addition to glycine, GABA, and taurine, play important roles in blood pressure control in conscious normotensive rats via central neural mechanisms and that the hypertension in renovascular hypertensive rats may involve a central abnormality.
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PMID:Central depressor effects of amino acids in conscious normotensive and two-kidney, one-clip renovascular hypertensive rats. 180 55

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

A series of acetyl-peptidyl-amides containing the amino acid sequence around the Arg-Ser kallikrein cleavage site of bovine kininogen were synthesized and tested for their ability to inhibit both the kinin-releasing activity and the amidase activity of purified human urinary kallikrein. The substrate analogues were competitive inhibitors for human urinary kallikrein and the heptapeptides (P4-P3'), hexapeptides (P3-P3'), and pentapeptides (P2-P3') gave Ki values of 140, 64, and 18 microM respectively, while the tetrapeptides (P1-P3'), tripeptides (P1'-P3') and dipeptides (P2'-P3') had little or no inhibitory activity. The effective analogues had neither kinin-like nor kinin-blocking activity on the rat uterus either before or after exposure to human urinary kallikrein. The effective human urinary kallikrein inhibitors were further examined for their effect on other serine proteases, including human plasma kallikrein, plasmin, complement components (C1s, C1r), bovine coagulation factors (IIa, IXa, and Xa), elastase, and trypsin. These peptides showed little inhibition of the circulating serine proteases but yielded a Ki for the nonspecific protease trypsin in the microM range. These results should provide the basis for the development of highly specific tissue kallikrein inhibitors to aid in elucidating the in vivo role(s) of tissue kallikreins.
Hypertension
PMID:Specificity of substrate analogue inhibitors of human urinary kallikrein. 384 67

The effects of furosemide and captopril were studied in nephrectomized rats with and without submaxillary gland. Captopril increased blood flow, but did not modified blood pressure. Furosemide plus captopril decreased significantly blood pressure. These results suggest a release of kallikrein by furosemide and probably a formation of kinin from plasma kininogen. On the other hand, rats sialodectomized showed no alterations in blood pressure in response to both drugs. These data suggest that submaxillary gland kallikrein participates in the mechanism of blood pressure regulation and blood flow of the gland at least in our experimental conditions. Glandular kallikreins are serine proteases which release kinins from substrates called kininogen. They are found in extracts and secretions of all exocrine glands. This proteases have been implicated in the regulation of exocrine glands and kidney blood flow, in water and electrolyte balance, in blood pressure regulation and in the pathogenesis of experimental and clinical hypertension (Carretero et al., 1978; Martinez Seeber et al., 1982). Glandular kallikreins of exocrine glands and kidney are secreted into the exocrine secretions and urine and also into the vascular compartment, where a local blood flow could be affected. According to Gautvik et al. (1980), rat submandibular gland is an organ rich in kallikrein, and significants amounts of the gland enzyme are release into the circulation after stimulation (Orstavik et al., 1982). Hilton and Lewis (1956) first proposed that glandular kallikrein-kinin system in salivary glands regulates vasodilation, probably through the effect of kallikrein on plasma kininogen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of furosemide and captopril on submaxillary gland blood flow and arterial pressure. 390 Oct 42

We studied the effect of aprotinin, a reversible inhibitor of kallikrein and other serine proteases, upon urinary kallikrein and kinin excretion, renal function and hemodynamics, blood pressure, and plasma renin activity (PRA). When aprotinin was administered to anesthetized rats at 10,000 KIU/kg as a bolus, and at 1000 KIU/kg/min infusion for 60 minutes, urinary kininogenase activity and immunoreactive kallikrein, kinins, sodium, potassium, and water excretion, and PRA decreased significantly. Aprotinin also caused a 36% decrease (p less than 0.001) in renal blood flow (RBF), and a 37% decrease (p less than 0.001) in glomerular filtration rate (GFR), although neither blood pressure nor cardiac output changed. The effect of aprotinin on PRA was further studied in conscious rats before and after stimulation of renin release by isoproterenol or furosemide. Aprotinin (5,000 KIU/kg bolus and 1000 KIU/kg/min infusion for 60 minutes) did not alter basal or isoproterenol-stimulated PRA, but it blunted the increase in PRA as stimulated by furosemide. Aprotinin at a higher dose (20,000 KIU/kg bolus and 5000 KIU/kg/min infusion for 60 minutes) significantly lowered blood pressure and increased hematocrit and PRA. These effects may be due to inhibition of serine protease(s) or to other as yet unrecognized properties of this peptide resulting from its highly cationic nature. In conclusion, aprotinin at a low dose decreased kallikrein, kinin, sodium, and water excretion. These decreases may be due to the inhibition of kallikrein and/or other serine proteases or may be secondary to the renal hemodynamic changes.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:The effect of aprotinin (a serine protease inhibitor) on renal function and renin release. 619 74


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