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)

It is documented that the number of leukocytes in peripheral blood increases considerably during pregnancy. We observed that the range of leukocytosis differs in normal pregnancy differs from that in cases with severe pregnancy induced hypertension (PIH). The data obtained in our university hospital, for example, give the number of leukocytes after twenty-four weeks of gestation as 9,000 +/- 1,600/mm3 (mean +/- SD) for normal cases (93 measurements in 37 cases) and 6,600 +/- 1,100/mm3 for PIH (72 measurements in 18 cases; p less than 0.001). To elucidate the cause and relation to PIH, we studied changes in the activity of leukocytes during pregnancy by means of a modified Nuclepore filtration method (Kikuchi et al., 1983). The time required for leukocytes to squeeze through filter pores under constant suction varies greatly depending on their active states; more active cells show greater resistance to pore passage, which can be clearly shown by exposing cells to various stimuli. The filtration time for 0.5ml blood containing 5,000/mm3 leukocytes minus that of leukocyte poor blood with the same hematocrit was taken as an index of the activity, which we called the rheological activity of leukocytes (RAL). RAL values for blood taken at delivery were 3.4 +/- 1.5 sec for normal cases and 5.0 +/- 2.1 sec for PIH (N.S.). RAL values obtained after the addition of a chemotactic stimulant FMLP (formyl-methionyl-leucyl-phenylalanine) (10nM) to the same samples were 21 +/- 10 sec for normal cases and 405 +/- 265 sec for PIH (p less than 0.001). Leukocyte activity, particularly, response to chemotactic stimulation, was the before thought to be considerably increased in PIH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Rheological analysis of suppressed leukocytosis in patients with pregnancy induced hypertension (PIH)]. 227 6

Angiotensin II has been reported to have both a positive inotropic effect and a coronary constrictor action in the hamster heart. To study the contribution to these responses of phenylalanine in position 8, we assessed the direct cardiac effects of angiotensin-(1-7), which lacks phenylalanine in position 8. Syrian hamsters were used to determine the effects of angiotensin-(1-7) on cardiac performance in the diseased and normal hearts. We used the isolated isovolumic heart preparation perfused either at a constant pressure of 50 mm Hg or at a constant coronary (myocardial) flow rate of 7 ml/min (seven cardiomyopathic hamsters [CMH] and seven normal hamsters [NH] in each subgroup). At constant perfusion pressure, coronary (myocardial) flow rate decreased (p less than 0.01) in both CMH and NH (-31 +/- 8% vs. -39 +/- 4% of baseline, respectively); but the percent decrease in left ventricular pressure and the first derivative of left ventricular pressure over time (LV + dP/dt) was significant only in NH (-8 +/- 1% and -9 +/- 4%) but not in CMH (-14 +/- 5% and -21 +/- 8%). On the other hand, at a constant coronary (myocardial) flow rate, left ventricular pressure and LV + dP/dt tended to increase in both CMH and NH (+10 +/- 3% and +6 +/- 2% of baseline vs. +7 +/- 7% and +7 +/- 5%, respectively) but these changes were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Feb
PMID:Biological activity of angiotensin-(1-7) heptapeptide in the hamster heart. 229 73

Pro-His-Pro-Phe-His-Statine-Ile-Phe-NH2 (R-Pep-27), a potent renin inhibitory peptide, was infused into the conscious, sodium-depleted Macaca fascicularis at doses of 0, 0.1, 1, 4, 16, and 32 micrograms/kg/min for 10 minutes. At all doses greater than 0.1 microgram/kg/min, there was a parallel decrease in mean arterial pressure (MAP), plasma renin activity, and plasma angiotensin II (Ang II) concentration. On the other hand, assays with monoclonal antibodies specific for total renin and active renin demonstrated that the peptide's inhibition of circulating active renin stimulated the release of both. The maximal effective R-Pep-27 dose was approximately 16 micrograms/kg/min, which reduced MAP by an average of 15.8 +/- 1.4 mm Hg (n = 14) and plasma renin activity and plasma Ang II concentration to 3% (n = 9) and 15% (n = 5), respectively, of the pretreatment values. At 0.1 microgram/kg/min, there was no significant decrease in MAP; however, measurement of plasma renin activity showed an average decrease in activity of 42% (n = 3). No significant change in the heart rate was observed at all the doses studied. For comparison, intravenous captopril (400 micrograms/kg bolus) was administered after the MAP of the monkeys had recovered from the peptide experiments, and it reduced MAP by 25.1 +/- 2.4 mm Hg (n = 10) without significantly changing plasma renin activity. As anticipated, injection of angiotensin I (80-160 ng/kg bolus) into sodium-depleted monkeys during peptide infusion caused a transient rise in MAP of 14.8 +/- 5.4 mm Hg (n = 4) above the mean pretreatment value.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1989 Nov
PMID:Effects of renin inhibition in the conscious primate Macaca fascicularis. 268 Sep 62

Earlier studies from this laboratory had indicated that there is a selective increase in the density of brain kappa opioid receptors labeled with [3H]ethylketocyclazocine in spontaneously hypertensive (SHR) rats in comparison to normotensive Wistar-Kyoto rats. The binding of a mu-ligand, [3H]naltrexone, and a delta-ligand, [3H]Tyr-D-Ser-Gly-Phe-Leu-Thr, to brain membranes of hypertensive and normotensive rats did not differ. The present studies were undertaken to determine further the role of kappa opioid receptors in hypertension. The binding of [3H]ethylketocyclazocine to brain membranes of hypertensive rats was much greater than those of normotensive rats. The density of kappa receptors was significantly higher in hypothalamic membranes of hypertensive rats as compared to normotensive rats. In order to determine the functional significance of the increased density of brain kappa opioid receptors in SHR rats, the effect of the kappa receptor agonists, tifluadom, U-50,488H and bremazocine, on two known actions associated with kappa receptors, namely analgesia and diuresis, were determined in SHR and normotensive rats. All three kappa agonists produced dose-dependent analgesia as measured by the tail-flick test. The intensity of the analgesic responses at each dose of the drugs in SHR rats was much greater than in normotensive Wistar-Kyoto rats. The kappa drugs also produced dose-dependent diuretic effects when the rats were loaded with 5% saline intragastrically. The increases in the volumes of urine produced by kappa drugs were much greater in SHR rats in comparison to normotensive rats. The basal tail-flick reaction time or urinary output in the two strains did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kappa opioid receptor activity in spontaneously hypertensive rats. 283 73

Specific atrial natriuretic factor (ANF) analogues have been found to have inhibitory activity in vitro in a calmodulin-dependent, human red blood cell membrane Ca2+-adenosine triphosphatase (ATPase) model. Studied at 10(-8) to 10(-6) M concentrations, atriopeptin I (residues 127-147 of rat prepro-ANF sequence) and atriopeptin III (residues 127-150) progressively inhibited Ca2+-ATPase activity by up to 20% (p less than 0.001). This degree of inhibition was consistent with activities of other (calmodulin-independent) enzyme inhibitors in this model. Therefore, the C-terminal Phe-Arg-Tyr sequence (residues 148-150) is unnecessary for atriopeptin action on Ca2+-ATPase. Human and rat atrial peptides with amino acids 123-150 were inactive, indicating that the 123-126 sequence (Ser-Leu-Arg-Arg) must be cleaved to activate atriopeptins in this system. Human ANF fragment 129-150 also had no effect on Ca2+-ATPase, defining the importance of residues 127-128 (Ser-Ser) proximal to the disulfide bridge (joining 129 to 145). The addition of purified calmodulin to red blood cell membranes in the presence of inhibitory ANF did not restore Ca2+-ATPase activity to normal levels, indicating that the ANF effect on this enzyme is calmodulin-independent. Atriopeptin I and atriopeptin III had no effect on red blood cell Na+, K+-ATPase activity in vitro. Thus, the structure-activity relationships of ANF analogues in this novel human cell membrane model are highly specific. Although the inhibitory action of ANF analogues on Ca2+-ATPase, a calcium pump-associated enzyme, may be unique to the red blood cell, the calcium dependence of the gluconeogenic effects of ANF in the kidney would be supported by inhibition of this ATPase.
Hypertension 1988 Oct
PMID:Analogue-specific action in vitro of atrial natriuretic factor on human red blood cell Ca2+-ATPase activity. 284 69

These experiments were designed to assess the interaction of bradykinin and its antagonist (Arg-Pro-Hyp-Gly-Phe-Ser-DPhe-Phe-Arg-trifluoroacetic acid) with the sympathoadrenal system. Three groups of male Wistar rats received 5-minute intra-arterial infusions of either dextrose (Group 1, n = 6), bradykinin, 250 micrograms/min (Group 2, n = 5), or bradykinin, 25 micrograms/min (Group 3, n = 4). Six other groups received a similar infusion of the bradykinin antagonist at 250 micrograms/min. They were either intact rats (Group 4, n = 10) or rats previously submitted to chemical sympathectomy (Group 5, n = 17), to adrenal enucleation (Group 6, n = 8), to combined alpha-adrenergic and beta-adrenergic blockade (Group 7, n = 7), to alpha 1-adrenergic receptor blockade (Group 8, n = 8), or to alpha 2-adrenergic receptor blockade (Group 9, n = 8). Bradykinin infusion produced a sustained fall in mean arterial pressure (MAP) in Groups 2 and 3 (by -48 +/- 3 and -36 +/- 7 mm Hg, respectively) associated with similar increases in plasma epinephrine levels (100-fold), and norepinephrine (sevenfold) as compared with Group 1. The bradykinin antagonist infusion in intact rats produced a 23 +/- 4 mm Hg rise in MAP associated with a sixfold increase in epinephrine and a twofold increase in norepinephrine. Group 5 rats with lower baseline catecholamine levels had an even larger MAP rise (30 +/- 6 mm Hg) accompanied by a rise in epinephrine and norepinephrine proportionally similar to that of intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1988 Jun
PMID:Vascular and sympathoadrenal responses to bradykinin and a bradykinin analogue. 289 59

The renal and hypotensive responses to intravenous infusions of 10, 50, 100, and 200 pmol/kg/min of synthetic rat atrial natriuretic factor (Arg101-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile110-Asp-Arg-Ile-G ly-Ala-Gln-Ser-Gly -Leu-Gly120-Cys-Asn-Ser-Phe-Arg-Tyr; disulfide bond between cysteines) were compared with those produced by synthetic human atrial natriuretic factor (Met110) in five conscious dogs. Increasing doses of rat or human atrial natriuretic factor lowered mean arterial pressure in a dose-related manner. At 200 pmol/kg/min, the maximally effective dose for both peptides, mean arterial pressure was reduced from 116 +/- 4 to 96 +/- 5 mm Hg and from 117 +/- 5 to 100 +/- 3 mm Hg (p less than 0.01), respectively. Neither peptide affected heart rate. Fractional sodium excretion increased from 0.69 +/- 0.22 to 3.95 +/- 1.23% and from 0.69 +/- 0.16 to 4.62 +/- 0.72% during infusions of 200 pmol/kg/min of rat and human atrial natriuretic factor, respectively. Urine volume and fractional chloride excretion rose during infusions of rat or human atrial natriuretic factor in a manner that resembled the elevation in sodium excretion. The stimulation of fractional potassium excretion by both rat and human peptides was more variable and not as clearly dose-dependent. Glomerular filtration rate was enhanced by both rat and human atrial natriuretic factor, while neither peptide significantly changed renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1986 Mar
PMID:A comparison of synthetic rat and human atrial natriuretic factor in conscious dogs. 293 82

alpha-Human atrial natriuretic peptide (hANP) is secreted by the heart and acts on the kidney to promote a strong diuresis and natriuresis. In vivo it has been shown to be catabolized partly by the kidney. Crude microvillar membranes of human kidney degrade 125I-ANP at several internal bonds generating metabolites among which the C-terminal fragments were identified. Formation of the C-terminal tripeptide was blocked by phosphoramidon, indicating the involvement of endopeptidase-24.11 in this cleavage. Subsequent cleavages by aminopeptidase(s) yielded the C-terminal dipeptide and free tyrosine. Using purified endopeptidase 24.11, we identified seven sites of hydrolysis in unlabelled alpha-hANP: the bonds Arg-4-Ser-5, Cys-7-Phe-8, Arg-11-Met-12, Arg-14-Ile-15, Gly-16-Ala-17, Gly-20-Leu-21 and Ser-25-Phe-26. However, the bonds Gly-16-Ala-17 and Arg-4-Ser-5 did not fulfil the known specificity requirements of the enzyme. Cleavage at the Gly-16-Ala-17 bond was previously observed by Stephenson & Kenny [(1987) Biochem. J. 243, 183-187], but this is the first report of an Arg-Ser bond cleavage by this enzyme. Initial attack of alpha-hANP by endopeptidase-24.11 took place at a bond within the disulphide-linked loop and produced a peptide having the same amino acid composition as intact ANP. The bond cleaved in this metabolite was determined as the Cys-7-Phe-8 bond. Determination of all the bonds cleaved in alpha-hANP by endopeptidase-24.11 should prove useful for the design of more stable analogues, which could have therapeutic uses in hypertension.
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PMID:Hydrolysis of alpha-human atrial natriuretic peptide in vitro by human kidney membranes and purified endopeptidase-24.11. Evidence for a novel cleavage site. 297 76

Synthetic atrial natriuretic factor (Arg-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly -Leu- Gly-Cys-Asn-Ser-Phe-Arg-Tyr-COOH [disulfide bond between cysteines]) was infused intravenously into conscious normotensive and deoxycorticosterone, one-kidney, one-clip, and two-kidney, one-clip hypertensive rats. Mean arterial pressure, urine volume, and electrolyte excretion rates were measured during a 20-minute infusion of a single dose (ranging from 0-1520 pmol/min) into each animal; 95 to 380 pmol/minute of synthetic atrial natriuretic factor maximally reduced mean arterial pressure by -20 +/- 4, -29 +/- 2, and -39 +/- 7 mm Hg in normotensive, one-kidney, one-clip, and two-kidney, one-clip hypertensive rats, respectively. In deoxycorticosterone rats, a dose of 760 pmol/minute was required to produce the largest depressor response (-58 +/- 12 mm Hg). Sodium excretion increased to 8.8 +/- 2.5 muEq/minute at 760 pmol/minute in normotensive rats, to 6.5 +/- 1.1 muEq/minute at 50 pmol/minute in deoxycorticosterone rats, and to 5.8 +/- 1.5 muEq/minute at 95 pmol/minute in one-kidney, one-clip animals. The natriuretic effect was consistently greater at all doses of synthetic atrial natriuretic factor in the two-kidney, one-clip hypertensive model, in which the maximum response was 15.3 +/- 4.7 muEq/minute at 190 pmol/minute. The changes in urine volume and excretion rates of potassium and chloride tended to parallel the increases in sodium excretion in each model. Interestingly, the maximally effective hypotensive dose of synthetic atrial natriuretic factor was different from the maximally effective natriuretic dose in all four groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Synthetic atrial natriuretic factor in conscious normotensive and hypertensive rats. 298 24

In 15 patients with mild-to-moderate essential hypertension a new orally active angiotensin converting enzyme inhibitor, 1-(D-3-acetylthio-2-methylpropanoyl)-L-prolyl-L-phenylalanine (Alacepril), was administered with a single oral dose of 50 mg to evaluate its antihypertensive effect. Following Alacepril plasma angiotensin converting enzyme (ACE) activity was inhibited by approximately 75% within 2 h. Plasma renin activity increased slightly whereas plasma levels of aldosterone decreased significantly. Blood pressure fell markedly not only in patients with high renin levels but also in those with low renin levels. Nevertheless, the magnitude of blood pressure reduction was correlated with the pre-treatment plasma renin values (r = -0.602, p less than 0.05 systolic, r = -0.667, p less than 0.01 diastolic). No relevant changes in pulse rate was observed. These findings demonstrate that in essential hypertension the novel orally active ACE inhibitor Alacepril exerts marked antihypertensive effect, which may offer a new effective approach to treatment of hypertension.
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PMID:Acute effects of the new oral angiotensin converting enzyme inhibitor 1-(D-3-acetylthio-2-methylpropanoyl)-L-prolyl-L-phenylalanine (Alacepril) in essential hypertension. 299 86


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