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)

During the study of an inbred strain of Wistar rats which spontaneously develop hypertension when they reach a weight of approximately 150 g, it was found that these animals also develop an erythrocytosis. A significant increase in red cell count was observed in spontaneously hypertensive (SH) rats (8-11 x 10(6) RBC/mm(3)) when compared with normotensive rats (6-7 x 10(6) RBC/mm(3)) of the same strain. This increase in red cell count paralleled the increase in body weight and the rise in blood pressure. Since the plasma volume, as measured with labeled albumin was normal, there was an absolute increase in red cells. The hematocrit and hemoglobin content of the blood measured in SH rats were only slightly greater than those found in normotensive rats. However, the mean cell volume (MCV) of the red cells in the SH rats was 45-47 mu(3) as compared with 51-53 mu(3) in normotensive rats.A fourfold increase in 24 hr (59)Fe incorporation into the red cells was found in the SH rats when compared with normotensive controls. The bone marrow of the SH rats showed erythroid hyperplasia. When the SH rats were treated with alpha-methyldopa (Aldomet 200 mg/kg daily, i.p.) the red cell count fell in parallel with the drop in blood pressure. No change in red cell count or blood pressure was observed in normotensive rats treated in the same manner. The erythropoietin titer was high in SH rats, and was undetectable in normotensive rats. These observations suggest a direct relationship between the hypertension and the erythrocytosis mediated by erythropoietin; both are genetically controlled.
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PMID:Erythrocytosis in spontaneously hypertensive rats. 501 Nov 7

Overall, the worldwide experience on enalapril to date is very encouraging. The drug produces good to excellent responses in 54 to 66 percent of patients with essential hypertension and is at least as effective as either diuretics or beta blockers. The effects of enalapril compared with those of diuretics confirm that patients more dependent upon the renin-angiotensin system respond better. When hydrochlorothiazide is administered concomitantly with enalapril, almost all patients respond, with good long-term maintenance. In patients with severe hypertension, Blocadren or Aldomet may be added in addition to hydrochlorothiazide and will produce additional benefit. Enalapril attenuates the adverse metabolic effects of hydrochlorothiazide, particularly hypokalemia. Overall, although the efficacy of enalapril and that of captopril are similar, enalapril is better tolerated and does not appear to be associated with any significant occurrence of captopril-type side effects, particularly the skin rash and loss of taste. As expected, enalapril and other converting inhibitors may be associated with azotemia in patients with bilateral renovascular hypertension.
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PMID:Enalapril worldwide experience. 608 56

Clonidine (Catapres, Catapresan), guanfacine (Estulic), and methyldopa (Aldomet) are the prototypes of centrally acting antihypertensive drugs. Clonidine and guanfacine are lipophilic drugs that readily penetrate into the brain, where they stimulate alpha-adrenergic receptors in the pontomedullary region. The stimulation of these central alpha-adrenergic receptors has been shown to activate an inhibiting neuron, which causes a reduction of peripheral sympathetic tone and a subsequent fall in arterial blood pressure and heart rate. Both a centrally initiated reduction of vagus reflex activity and the activation of presynaptic alpha 2-adrenergic blocking agents in the heart may contribute to the bradycardia. Studies indicate that methyldopa also penetrates into the brain, where it is converted into alpha-methylnorepinephrine. This amine may stimulate the same central alpha-adrenergic receptors as those activated by clonidine, which will result in a hypotensive effect. Possibly, alpha-methyldopamine might also play a role. Accordingly, the modes of action of clonidine and alpha-methyldopa probably are very similar at a basic level. The central adrenergic receptors probably are located postsynaptically. Their receptor demand corresponds more closely to that of the alpha 2-subtype. Central alpha 1-adrenergic receptors might possibly play a part in the modulation of vagally induced baroreflex bradycardia. A discussion on the pharmacological basis of the side effects of the centrally acting antihypertensives has been limited to those adverse reactions that are somehow related to alpha-adrenergic receptors. Sedation, a common side effect, appears to be mediated by central alpha 2-adrenergic receptors, at least in animal models.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:The hypotensive activity and side effects of methyldopa, clonidine, and guanfacine. 609 46

Serial blood samples were obtained throughout pregnancy from 11 women with essential hypertension (EHT). Seven were treated with labetalol (Trandate) and 4 with alpha -methyl dopa (Aldomet). Nine patients were well-controlled throughout pregnancy. Their mean plasma renin concentrations (PRC) followed the profile determined in 18 normal patients studied serially. They remained in the upper normal range until the last month, when both treatment groups showed a fall in PRC. Mean plasma aldosterone (ALD) also followed a normal profile until late gestation when it too showed a sharp fall. Of the two patients who developed superimposed PIH, one, who received labetalol, developed severe hypertension at 35 weeks, requiring delivery. Although PRC increased early in this pregnancy, ALD did not, remaining low throughout. Serum potassium [K+] measurements were also very low in this patient. The second patient only became hypertensive at 40 weeks and had PRC and ALD profiles resembling those in the successfully treated EHTs. There was a strong positive correlation throughout between serum potassium and ALD measurements (p less than 0.001) but none between PRC and ALD. This latter agrees with the known lack of correlation between PRC and ALD in normal pregnancy and may suggest that changes in electrolyte balance are more important stimuli to ALD secretion during pregnancy.
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PMID:Renin and aldosterone concentrations in pregnant essential hypertensives - a prospective study. 634 44

Blood pressure; extracellular fluid volume; renal plasma flow; glomerular filtration rate; plasma concentrations of renin, angiotensin, aldosterone, desoxycorticosterone, and prostaglandins; responses to infused angiotensin; and many other factors are altered during normal and hypertensive gestation. The diagnosis of the exact disease process responsible for hypertension in pregnancy in an individual patient is extremely difficult if based solely on clinical criteria. The American College of Obstetricians and Gynecologists has suggested the following clinical classifications: (1) preeclampsia-eclampsia, (2) chronic hypertension of whatever cause, (3) chronic hypertension with superimposed preeclampsia, and (4) late or transient hypertension. The three broad categories of renal disease responsible for these clinical syndromes are: (1) preeclampsia-eclampsia, (2) hypertensive changes, and (3) various primary renal diseases. Controversy abounds regarding the aggressiveness of therapy in this syndrome. We prefer a middle-of-the-road approach, bringing blood pressure down to the range of 95 to 100 mm Hg. Hydralazine and Aldomet are the usual drugs of choice. Any intervening nervous system hyperexcitability suggests impending eclampsia and should be immediately treated with magnesium sulfate. The long-term prognosis for the mother with pure preeclampsia appears to be excellent. Most infants born of hypertensive gestations are small for date, with a prognosis that is also affected by the underlying disease of the mother.
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PMID:Hypertension in pregnancy. 655 34

We present the case of a 28-year-old man being treated with Nardil for chronic depression who developed a hypertensive crisis and a severe occipital headache one hour after ingesting an over-the-counter appetite suppressant. The adverse reactions between MAO inhibitors and phenylpropanolamine and discussed, as are the dangers of using Demerol to treat the headache and Aldomet to treat the hypertension.
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PMID:Hypertensive crisis resulting from an MAO inhibitor and an over-the-counter appetite suppressant. 711 95

Twentysix women with pregnancy-induced hypertension have been randomly treated with either labetalol or Aldomet. A more satisfactory control of blood pressure was obtained with labetalol with minimal side-effects. After two weeks of treatment with labetalol renal function had significantly improved with a markedly lower incidence of proteinuria. More patients went into spontaneous labour following labetalol than following Aldomet; the Bishop score was also higher in this group. No adverse effects attributable to labetalol were noted in the baby either ante- or post-natally.
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PMID:Comparison of the alpha and beta blocking drug, labetalol, and methyl dopa in the treatment of moderate and severe pregnancy-induced hypertension. 742 66

Aromatic alpha-amino-alpha-methyl acids and alpha-hydrazino-alpha-methyl acids are known aromatic amino acid decarboxylase inhibitors. Specific derivatives such as 2-amino-2-methyl-3-(3,4- dihydroxyphenyl)propanoate, Aldomet, and 2-hydrazino-2-methyl-3-(3,4- dihydroxyphenyl)propanoate, Lodosyn, have been developed as therapeutic agents to treat hypertension and Parkinson's disease, respectively. We recently reported a method for the kinetic resolution of the racemic esters of such compounds using a crude preparation of a novel enzyme catalyst from the yeast Candida lipolytica (Yee, C.; Blythe, T.A., McNabb, T.J.; Walts, A.E. J. Org. Chem. 1992, 57, 3525-3527). Here we report the purification and initial characterization of the active enzyme component, an enzyme given the name Candida lipolytica ester hydrolase (CLEH). CLEH was purified to > 95% homogeneity by chromatography on Matrex Blue B resin. The enzyme was found to be a glycoprotein with M(r) = 80,000-300,000. In addition to esterolytic activity, the enzyme was found to catalyze the hydrolysis of amides, anilides and peptides. Sequence analysis of internal peptides of CLEH revealed striking homology to a number of enzymes belonging to the group of serine carboxypeptidases (E.C. 3.4.16.1). One peptide aligned with the canonical serine carboxypeptidase active site sequence, GESYAG. Based on the structural relationship of CLEH to serine carboxypeptidases, three representative serine carboxypeptidases were evaluated for their utility in resolving racemic alpha-tertiary ester substrates and compared with the activity of CLEH. All enzymes revealed similarly high activity and enantioselectivity towards the alpha-hydrazino-alpha-methyl ester precursor of the Parkinson-drug Carbidopa. However, differences in enantioselectivity were observed with other alpha-tertiary-substituted ester substrates. Serine carboxypeptidase-catalyzed ester resolutions thus offer a new route to many sterically hindered homochiral alpha-amino, alpha-hydrazino and alpha-hydroxy carboxylic acids.
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PMID:Enzymes for the resolution of alpha-tertiary-substituted carboxylic acid esters. 785 60

QuestionQuite a few of my pregnant patients have hypertensive disorders. What is the threshold for treating hypertension during pregnancy? Which of the various antihypertensive agents are considered safe during pregnancy?AnswerPharmacologic therapy could benefit mother and baby when diastolic pressure exceeds 110 mm Hg. Preeclampsia must be followed closely. Methyldopa (eg, Aldomet) and hydralazine (eg, Apresoline) are still the drugs of choice during pregnancy, although the safety and efficacy of calcium channel blockers and Beta-blockers appear well established.
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PMID:Therapeutic approach to hypertension during pregnancy. 964 May 15

The incidence, pathogenesis and management of hypertension in 1600 pregnant women admitted to El-Hussein University Hospital, Cairo, in 1980 was studied. A total of 100 women had pregnancy related hypertension, e.g.: 67 or 4.18% had pre-eclampsia, 7 or .44% had eclampsia, 25 or 1.56% had essential hypertension, and 1 or .06% had chronic nephritis. Total fetal mortality was 18%. Maternal mortality was 2% in all cases. Maternal complications or morbidity was 14: 10 in pre-eclampsia; 1 in eclampsia; and 3 in essential hypertension. From all pathological states 54 patients ended with spontaneous vaginal delivery. Termination of pregnancy occurred only in 2 patients, one with severe pre-eclampsia and the other with severe essential hypertension. Induction of labor was done in different weeks of gestation according to the severity or complications discovered. Caesarean section was done in 12 patients, 7 of them for hypertension and in the remaining 5 for other reasons. Management of hypertension at the hospital consisted of 3 approaches: 1) rest in bed and sedation such as pethidine, valium or Algafan; 2) a combination of sedatives and hypotensives such as Brinerdin, Serpasil and Aldomet; and 3) a combination of sedatives, hypotensives and diuretics.
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PMID:Al-Azar experience in pregnancy associated hypertension. 1226 17


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