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

We studied the role of the sympathetic nervous system in the antihypertensive actions of taurine in DOCA (deoxycorticosterone acetate)-salt hypertensive rats. Supplementation with 1% taurine could moderate the development of the DOCA-salt hypertension. Norepinephrine turnover was measured from the rate of decline of tissue norepinephrine concentration after the administration of alpha-methyl-p-tyrosine. Cardiac and splenic norepinephrine turnover was markedly accelerated in the DOCA-salt rats compared with the vehicle-treated control rats, but the 1% taurine supplements could normalize this. These results suggest that the normalization of the increased sympathetic activity may be involved in the antihypertensive actions of taurine in DOCA-salt hypertensive rats.
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PMID:The antihypertensive effect of taurine in DOCA-salt rats. 615 84

Rabbit brain endo-oligopeptidase B inactivates angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) and angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) by hydrolysis of the Pro7-Phe8 peptide bond. The site of hydrolysis was determined in preparative and analytical experiments in which both products were recovered in a molar ratio of 1:1, and the sum of the products plus unhydrolyzed substrate accounted for the starting material. The enzyme has a Km of 6.3 x 10(-5) M for angiotensin II at pH 8.3 and is activated 30-fold with 4.8 mM dithiothreitol. BPP9a ( less than Gln-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, SQ 20,881) inhibits the inactivation of angiotensin II with an I50 of 5 x 10(-5) M. BPP5a (less than Gln-Lys-Trp-Ala-Pro, SQ 20,475) is less active and D-3-mercapto-2-methylpropanoyl-L-proline (captopril, SQ 14,225) has essentially no activity. These endo-oligopeptidase B in angiotensin I and II metabolism remains to be established.
Hypertension
PMID:Brain endo-oligopeptidase B: a post-proline cleaving enzyme that inactivates angiotensin I and II. 617 71

Arginine-vasopressin (AVP), the antidiuretic hormone, not only regulates water balance but may also exert direct and indirect effects on blood pressure by influencing systemic vascular resistance and body fluid volumes. Recently, specific competitive antagonists of AVP at its vascular and tubular receptors have been described. We used d(CH2)5Tyr(Me) AVP, a vascular (V1) antagonist, and d(CH2)5-D-Tyr(Et) VAVP, a vascular and tubular (V1V2) antagonist, for studies on the role of AVP in deoxycorticosterone acetate (DOCA)-salt hypertension. The antagonists were infused intravenously via osmotic minipumps in unilaterally nephrectomized rats for 6 weeks after the beginning of the DOCA-salt treatment. At the end of the experiment, blood pressure was 15 mm Hg lower in the rats receiving the V1 antagonist than in those in which the vehicle was infused. In the rats receiving the V1V2 antagonist, blood pressure was reduced by 38 mm Hg. However, these rats were in poor general condition and gained no body weight. Their plasma sodium concentration was markedly increased throughout the duration of the experiment. These results suggest that AVP contributes to the development of DOCA-salt hypertension not only through its vascular but also through its renal tubular effects. Thus AVP may act as an impormediator of volume changes associated with alterations in sodium intake or excretion and thereby affect blood pressure.
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PMID:Endocrine control of salt and water excretion: the role of vasopressin in DOCA-salt hypertension. 620 39

The antidiuretic hormone, arginine-vasopressin (AVP), may participate in the regulation of blood pressure (BP) through its vasoconstrictor effects. In anesthetized rats, exogenous AVP induced stronger vasoconstriction in the mesenteric than in the renal vascular bed. Conversely, mesenteric but not renal vascular resistance was reduced by a vascular antagonist of AVP, d(CH2)5 VDAVP, in rats with increased endogenous AVP after anesthesia, dehydration, or injection of glycerol. Another vascular AVP-antagonist, d(CH2)5 Tyr (Me) AVP, induced a transient fall in BP in conscious primates (marmosets) after diuretic-induced volume depletion. In conscious rats with established deoxycorticosterone acetate (DOCA)/salt hypertension, d(CH2)5 Tyr (Me) AVP decreased systolic BP after acute administration. After chronic administration of this antagonist during 6 weeks after the beginning of DOCA/salt treatment, the severity of hypertension was reduced. When another, AVP-antagonist, d(CH2)5-D-Tyr (Et) VAVP, which blocks vascular and renal tubular AVP-receptors, was administered chronically, the development of DOCA/salt hypertension was prevented at the expense of severe and persistent hypernatremia. These results demonstrate that under certain conditions the vascular effects of AVP may contribute to the maintenance of BP, AVP appears to participate in the pathogenesis of DOCA/salt hypertension through both its vasoconstrictor and its antidiuretic effects.
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PMID:The significance of vasopressin as a pressor agent. 620 52

We have studied inhibition of homogeneous human converting enzyme by a new inhibitor, a ketomethylene derivative of the blocked tripeptide substrate, Bz-Phe-Gly-Pro (ketoACE). KetoACE inhibited the hydrolysis of Hip-His-Leu and Hip-Phe-Arg at different concentrations (I50 values were 4 X 10(-8) M and 2 X 10(-7) M, respectively). Kinetic studies indicated that ketoACE inhibits the hydrolysis of both substrates by a similar, non-competitive mechanism. At the lowest enzyme concentration tested, using 3H-Hip-Gly-Gly as substrate, the I50 of ketoACE was 6 X 10(-9) M. KetoACE protected a functional tyrosine residue in the active site of human converting enzyme from modification with N-acetylimidazole. It is proposed that there are alternate (hydrophobic) binding sites for both inhibitors and substrates in the active site of human converting enzyme. It should be possible to develop other high-affinity inhibitors of this class that bind to hydrophobic sites and do not require metal binding via a sulfhydryl group.
Hypertension
PMID:Inhibition of human converting enzyme in vitro by a novel tripeptide analog. 626 59

The widespread clinical study of converting-enzyme inhibitors has shown that they are effective antihypertensive drugs even in patients who may manifest either normal or decreased plasma renin activity. This suggests either that renin in a site other than plasma may play a contributory role in essential hypertension or that the hypotensive effect is caused by increased concentrations of kinins and prostaglandins, both demonstrated consequences of converting-enzyme inhibitor administration. Specific renin inhibitors appropriate for studies in humans would aid in the resolution of this question. Four classes of compounds have been demonstrated to be renin inhibitors of high potency: specific antibody, general peptide inhibitors of acid proteases, analogs of angiotensinogens, and peptides that are related to the amino-terminal sequence of prorenin. With the purification of renin, specific polyclonal or monoclonal antibodies have become available. The former have already been used extensively in physiologic studies in intact animals. Pepstatin is an inhibitor of many acid proteases. Its in vivo application has been retarded by its relative insolubility, but recent chemical modifications, particularly the addition of charged amino acids at the carboxy terminus, have rendered it more useful. The minimal substrate for renin is an octapeptide segment of the protein substrate: His-Pro-Phe-His-Leu-Leu-Val-Tyr. Variants of this sequence have resulted in competitive inhibitors that are useful in vivo. Recently, remarkably active inhibitors have been synthesized by reducing the peptide bond that is cleaved by renin, producing what may be a transition state inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Is renin a factor in the etiology of essential hypertension? 641 50

Renal denervation has been shown previously to lower the increased arterial pressure as well as the increased hypothalamic and peripheral noradrenergic activity found in neurogenic and Goldblatt models of experimental hypertension. In the present study conscious Wistar rats with or without renal nerves were subjected to 60 min of saline infusion (controls), hypotension (intravenous sodium nitroprusside), or hypertension (intravenous phenylephrine HCl). Changes in the turnover of norepinephrine (NE) in the anterior hypothalamus, posterior hypothalamus, kidney, intestine, and skeletal muscle were assessed by measuring the decline of NE concentration 90 min after administration of alpha-methyl tyrosine. There was a significant increase in NE turnover in the posterior hypothalamus and all peripheral organs examined in the nitroprusside-infused group with intact renal nerves. In renal-denervated animals, acute hypotension produced similar changes in NE turnover in peripheral organs, but no significant change was observed in the posterior hypothalamus. In the acutely hypertensive group with intact renal nerves, there was no significant change in NE turnover in the hypothalamic sections or the peripheral organs; however, the turnover of NE was significantly decreased in both the anterior and posterior hypothalamus of the renal-denervated hypertensive group. Overall these studies suggest the presence of an interaction between inhibitory influences from baroreceptor afferents and excitatory influences from renal afferents on noradrenergic activity in the hypothalamus and changes in noradrenergic activity in hypothalamic structures may not be directly related to changes in sympathetic outflow.
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PMID:Influence of renal nerves on noradrenergic responses to changes in arterial pressure. 649 10

To examine the hypothesis that abnormalities of noradrenergic innervation of hypothalamic pressor areas influence the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR), the norepinephrine content of individual hypothalamic and brainstem nuclei was determined in SHR and control Wistar-Kyoto (WKY) rats at 5, 7, and 11 weeks of age. At 5 and 7 weeks of age, the norepinephrine content of the posterior hypothalamic area (PHA) of SHR was significantly greater than that of WKY controls. These changes occurred at a time when blood pressure was not significantly different between the two groups. The increase in the norepinephrine content of the PHA was accompanied by increases in the norepinephrine content of the A1 region and locus coeruleus in 5-week SHR. In seven week old animals, studies of norepinephrine turnover using alpha-methyl-p-tyrosine revealed no differences between SHR and WKY in turnover in the PHA. The increase in norepinephrine content of the PHA in the absence of changes in turnover is interpreted to indicate increased noradrenergic input to the PHA of SHR and supports the hypothesis that noradrenergic pathways to the PHA are important in the development of hypertension in this model.
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PMID:The role of the posterior hypothalamic area in the pathogenesis of hypertension in the spontaneously hypertensive rat. 651 92

Experimental evidence indicates that arginine vasopressin (AVP) may contribute to the rise of blood pressure (BP) in hypertension induced by renal failure and sodium overload. We studied the AVP inhibitor [1-(B-mercapto-B,B-cyclopentamethylenepropionic acid)-2-(O-methyl)tyrosine] AVP in 12 normal and seven hypertensive subjects with end-stage renal disease. To test the agent's capacity to block the pressor action of exogenous AVP In humans, we constructed a dose-response curve with AVP doses of 1 to 20 mU/kg, raising BP by up to 30 mm Hg. Subsequently, five volunteers receive intravenous (i.v.) doses of 0.1 mg, and five volunteers received 0.5 mg of the inhibitor. The dose-response curve was then repeated with AVP doses up to 200 mU/kg. Both doses of the inhibitor shifted the curve to the right and downward, with the BP response to 20 mU/kg AVP being inhibited by 23% and 80% respectively. The duration of action of the compound was tested in two additional subjects, and was found to be over 3 hours. We then tested the compound in seven hypertensive patients with end-stage renal failure. Two days before dialysis, patients received a 150 mEq/day Na diet. After an additional Na load of 180 mEq via i.v. saline over 3 hours under constant BP and ECG monitoring, they received an i.v. bolus of 0.5 mg AVP inhibitor. A moderate BP fall occurred in five patients; it was maximal at 45 to 60 minutes and returned to baseline by 70 to 90 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Effects of a specific inhibitor of the vascular action of vasopressin in humans. 654 12

Apart from the problems of preparation for surgery, the difficulties lie mainly in general anaesthesia. Blood pressure variations and cardiac arrhythmias must be prevented. Anaesthesia must be given with a lot of care and must be deep, and some stages are particularly dangerous: induction, intubation (it is best to give a local anaesthetic with lignocaine), manipulation during dissection which should be very gentle, ablation of the tumour or clamping the draining veins. Treatment of the arrhythmias detected on ECG monitoring is based mainly on the use of lignocaine. Continuous monitoring of intra-arterial pressure is used to detect any variation. Only the severe bouts of hypertension need correction with phentolamine or nitroprussiate. In cases of shock, the essential point of management is to reestablish an adequate circulating volume: intravenous fluids are best given with control of pulmonary pressures which allows dangerous overload to be avoided. The specific problem of malignant pheochromocytoma is two-fold: treatment of the hypertension, at best with alpha-methyl-tyrosine or otherwise, with labetolol or prazosine, and treatment of the tumour, which has still not been resolved, and for which trials of chemotherapy are in progress.
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PMID:[Treatment of pheochromocytoma]. 662 24


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