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)

Considerable neuroanatomical and pharmacological evidence suggests that preproenkephalin A-derived peptides, particularly methionine-enkephalin, are involved in regulation of the cardiovascular system in both physiological and pathological states. In this study, we used a rat preproenkephalin A complementary DNA to determine whether proenkephalin A-derived peptides participate in the pathogenesis of hypertension as reflected by brain regional messenger RNA levels. Complementary DNA clones of the rat preproenkephalin A mRNA and rat small myelin basic protein mRNA were hybridized to total RNA extracted from hypothalamus, pons-medulla, thoracic cord, midbrain, and cerebellum of 3 1/2-week-old and 12-week-old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. In 3 1/2-week and 12-week animals there were no differences in the levels of myelin basic protein messenger RNA between the two groups in any brain region. At 3 1/2 weeks, preproenkephalin A mRNA levels did not differ between normotensive and hypertensive strains. In contrast, at 12 weeks preproenkephalin A mRNA levels were increased in hypothalamus, midbrain, thoracic cord, and cerebellum of SHR relative to WKY. Preproenkephalin A mRNA was significantly reduced in the pons-medulla of SHR relative to WKY. Our findings provide evidence that alterations in brain regional preproenkephalin A mRNA levels are associated with the development of spontaneous hypertension in the rat.
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PMID:Rat brain regional preproenkephalin A messenger RNA levels are altered in genetic hypertension. 247 7

The present study was carried out to investigate the effects of enkephalins (methionine-enkephalin: Met-Enk, leucine-enkephalin: Leu-Enk) on the adrenergic neurotransmission in hypertension. Perfused mesenteric vasculatures were prepared in spontaneously hypertensive rats (SHR, Okamoto and Aoki strain, 7-10 weeks old) and age-matched Wistar Kyoto rats (WKY), and the effects of these peptides on vascular responsiveness as well as norepinephrine release from the sympathetic nerve endings were examined. Pressor responses to electrical nerve stimulation were inhibited in a dose-dependent manner by Met-Enk and Leu-Enk, and the inhibition was antagonized by naloxone. Norepinephrine release during electrical nerve stimulation was also suppressed by these peptides. In SHR, stimulation-evoked pressor responses and norepinephrine release were significantly enhanced compared to those in WKY, while the suppressive magnitudes of the responses by Met-Enk and Leu-Enk were smaller in SHR than in WKY. These results demonstrate that Met-Enk and Leu-Enk affected presynaptic sites of blood vessels and caused a decrease in electrically-stimulated norepinephrine release from the sympathetic nerve endings. The lower reduction in norepinephrine release and vascular responsiveness by Met-Enk and Leu-Enk in SHR suggests an insufficient regulation of the vascular adrenergic neurotransmission by the opioid peptides in this model of hypertension.
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PMID:Inhibition of adrenergic transmission by methionine- and leucine-enkephalins is impaired in the mesenteric vasculatures of spontaneously hypertensive rats. 254 37

1. We examined the preganglionic splanchnic nerve activity and postganglionic renal nerve activity before and after a local injection of naloxone (20 micrograms/kg) into the coeliac ganglion of anaesthetized rabbits. This was done during graded hypertension, induced by the administration of phenylephrine (0.5-10 micrograms/kg, i.v.) and with selective intraganglionic injection of methionine-enkephalin (ME) and bunitrolol, which is a beta-blocker. 2. During hypertension both pre- and postganglionic discharge decreased, but only postganglionic discharge was inhibited by naloxone treatment into the ganglion. 3. Local injection of ME (0.1-10 micrograms/kg) into the coeliac ganglion decreased postganglionic activity by 9.0 +/- 1.0 to 41.2 +/- 4.7% from control, and this decrease was inhibited by naloxone. 4. Administration of bunitrolol (1-300 micrograms/kg) decreased postganglionic discharge by 3.9 +/- 1.4 to 39.7 +/- 2.4% of the control and this decrease was also inhibited by naloxone. 5. These results suggest that opioid receptors in the coeliac ganglion play an inhibitory role in neural ganglionic transmission and that this inhibitory action reduces postganglionic sympathetic discharge.
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PMID:Opioid receptor modulation of neural transmission in the rabbit coeliac ganglion and ganglionic opioid receptor activation by bunitrolol. 257 65

Few studies have presented a thorough analysis of young adults with symptoms of arterial occlusive disease. To learn more about the possible risk factors of vascular disease playing a role in these young patients, we have reviewed all patients of 45 years of age and younger with symptoms of arterial occlusive disease who had been referred to our department between 1978 and 1987. Thirty-seven patients (28 males and 9 females) were included in the study. The mean age at which the first symptoms occurred was 34 years. Most patients presented with chronic arterial obliterations of the lower extremities (31/37, 84%). In addition, 4 patients showed signs of ischaemic heart disease. A strongly positive family history of arteriosclerosis was obtained from 13 patients (35%). Hypertension was present in 7 patients (19%), diabetes in three (8%) and nicotine abuse was found in 27 patients (73%). Fifty-four percent of the patients (20/37) had undergone vascular reconstructive surgery, 19% (7/37) underwent transluminal dilatation, and 3 had had subsequent treatment of newly developed lesions. For this study, all patients were recalled to the outpatient clinic. A complete case history was taken followed by a physical examination and ECG. Laboratory examinations were performed to analyse parameters of: (a) coagulation; (b) fibrinolysis; (c) fat- and (d) methionine metabolism. Clear-cut laboratory abnormalities were found in 33 patients (33/37, 89%). Coagulation parameters were abnormal in 11 patients (30%) (protein S deficiency: 3 pts). Fibrinolysis was impaired in 15 patients (40%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A prospective survey of risk factors in young adults with arterial occlusive disease. 274 53

Recently we reported that the contractile agonist angiotensin II induces hypertrophy, not hyperplasia, in cultured rat aortic smooth muscle cells (Geisterfer AAT, Peach MJ, Owens GK: Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res 1988;62:749-756). We have further explored the hypothesis that contractile agonists are important regulators of smooth muscle cell growth by examining the effects of another contractile agonist, arginine vasopressin, on growth of cultured rat aortic smooth muscle cells. Autoradiographic analysis as well as cell number determinations showed that arginine vasopressin (1 microM) did not stimulate proliferation in cells made quiescent in a defined serum-free media nor did it augment proliferation in 0.4% fetal bovine serum. However, flow cytometric analysis of cellular protein content demonstrated that arginine vasopressin (1 microM) did induce cellular hypertrophy in quiescent cultures after 4 days of treatment, increasing smooth muscle cell protein content by 35% as compared with vehicle-treated controls. The increase in protein content showed a concentration dependence. Cellular hypertrophy was accompanied by an increase in [35S]methionine incorporation, which was elevated 45% by 24 hours. Both the increase in [35S]methionine incorporation and the increase in protein content could be prevented by the specific arginine vasopressin receptor antagonist. [1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine] arginine vasopressin. An increase in [35S]methionine incorporation was observed between 12 and 24 hours after treatment of quiescent smooth muscle cells for only 5 minutes with arginine vasopressin (1 microM). Arginine vasopressin-induced increases in [35S]methionine incorporation was increased within 6 hours after treatment. These studies show that arginine vasopressin, like angiotensin II, induces hypertrophy but not hyperplasia of cultured rat aortic smooth muscle cells.
Hypertension 1989 Oct
PMID:Arginine vasopressin-induced hypertrophy of cultured rat aortic smooth muscle cells. 279 15

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

We investigated the effects on blood pressure of 5% taurine administered prenatally or postnatally via maternal parents in stroke-prone spontaneously hypertensive rats (SHRSP). Prenatal and/or postnatal administration of taurine produced a blood pressure reduction in the offspring until at least 3 months of age. Furthermore, offspring exposed to high concentrations of taurine through the placenta during the prenatal period and also for 1 month after birth via maternal milk, showed a greater reduction in blood pressure than the group given taurine prenatally but not postnatally. The stroke-prone SHR were fed a high-fat cholesterol and low-protein diet containing 1% methionine or with 3% lysine in drinking water, and effects of the dietary amino acids on the development of atherogenesis were investigated. Intake of additional 1% methionine or 3% lysine had marked preventive effects on atherogenesis in the cerebral and mesenteric arteries in SHRSP. Therefore, early dietary intake of sulphur amino acids delays the onset of hypertension and attenuates the development of both severe hypertension and atherosclerosis in SHRSP.
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PMID:Effects of sulphur amino acids on the development of hypertension and atherosclerosis in stroke-prone spontaneously hypertensive rats. 348 15

The effects of either hypotension induced by sodium nitroprusside or hexamethonium or hypertension produced by angiotensin II or noradrenaline on the circulating levels of methionine enkephalin ([Met]enkephalin)-like immunoreactivity (MLI), adrenaline and noradrenaline in anaesthetized greyhounds were examined. Nitroprusside infusions (200 and 400 micrograms min-1) induced a fall in blood pressure accompanied by significant rises in plasma MLI and catecholamine concentrations. Concomitant administration of a high dose of naloxone did not alter the fall in blood pressure produced by nitroprusside but was associated with greater rises in circulating MLI and catecholamines when compared to nitroprusside alone, suggesting that [Met]enkephalin is not involved in the hypotensive action of nitroprusside. Intravenous hexamethonium (2.5 mg kg-1) provoked a fall in blood pressure which was not associated with any changes in plasma MLI. However, it produced a fall in plasma noradrenaline and a rise in plasma adrenaline. Thus it appears that neural mechanisms are required, at least in part, for the release of MLI. Angiotensin II (1.25 micrograms kg-1 min-1) and noradrenaline (8 micrograms kg-1 min-1) infusions produced an elevation in blood pressure without altering the circulating MLI levels. Study of the molecular forms of circulating MLI, before and during hypotension, revealed that the large molecular weight enkephalin-containing peptides with approximate molecular sizes of 18kD and 8kD were the predominant forms both in the basal and stimulated states. It is concluded that circulating [Met]enkephalin is not involved in the tonic control of blood pressure but it may modulate catecholamine release following hypotension as part of the stress response.
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PMID:Circulating [Met]enkephalin and catecholamine responses to acute hypotension and hypertension in anaesthetized greyhounds. 359 68

Autonomic dysfunction, including arrhythmias, has been shown to be associated with epileptogenic activity. This study examines the potential role for enkephalins in this process. A long lasting elevation of immunoreactive methionine (met)-enkephalin content in the septum, hypothalamus, amygdala, and hippocampus of rats occurs after pentylenetetrazol-induced convulsions (Brain Research 297: 121-125, 1984). Brennan et al (Life Sciences 27: 1097-1101, 1980) reported a greater percent inhibition of potassium-stimulated GABA release with increasing concentrations of met-enkephalin. Snead and Bearden (Science 210: 1031-1033, 1980) found that leucine-enkephalin in the central nervous system may induce epileptogenic activity. In addition, (d-alanine2) met-enkephalin has been shown to produce a centrally mediated vasopressor response as well as attenuation of the baroreceptor reflex in conscious cats (Hypertension 3: 395-407, 1981), possibly leading to autonomic imbalance. The latter may precipitate arrhythmias and sudden unexplained death in the epileptic patient. Resolution of the question of whether enkephalins elicit epileptogenic activity and autonomic dysfunction via inhibition of GABA release is important since an understanding of this mechanism should eventually allow the design of pharmacologic agents to prevent the epileptogenic activity, autonomic dysfunction and the associated sudden death.
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PMID:The role of enkephalins in the production of epileptogenic activity and autonomic dysfunction: origin of arrhythmia and sudden death in the epileptic patient? 361 1

Enkephalins are found in the posterior pituitary, can alter vasopressin secretion, and have greater pressor effects in spontaneously hypertensive rats (SHR) than in Wistar-Kyoto (WKY) rats. Measurement of the plasma methionine-enkephalin concentration (PMet-Enk) has provided equivocal results in humans and has not been reported in rats. We have developed a highly specific and sensitive Met-Enk radioimmunoassay and determined that Met-Enk circulates in rats but that PMet-Enk is no different between SHR and WKY rats (7.6 +/- 0.8 and 9.2 +/- 0.8 pg/ml, respectively). Water deprivation for 48 h increased the plasma vasopressin concentration (PADH) and 24-h urinary vasopressin excretion (UADHV) in SHR and WKY rats, but PMet-Enk was not altered. There were no differences in PADH and UADHV between SHR and WKY rats in either the euhydrated or dehydrated state. These results suggest that it is unlikely that circulating Met-Enk contributes importantly to the maintenance of hypertension in SHR. There was also no evidence for a greater secretion of vasopressin in SHR than in WKY rats, in contrast to previous reports.
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PMID:Methionine-enkephalin and vasopressin in SHR: effects of dehydration. 371 73


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