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)

The effects of leumorphin, a kappa-agonist derived from proenkephalin B (neoendorphin and dynorphin precursor), on vasopressin secretion were studied under basal and stimulated conditions in conscious, unrestrained rats. Intracerebroventricular injection of leumorphin (60 or 600 pmol) significantly inhibited basal vasopressin secretion. The vasopressin response induced by intracerebroventricular injection of angiotensin II (100 pmol) was significantly suppressed, in a dose-dependent fashion, by the simultaneous intracerebroventricular injection of leumorphin (6, 60, or 600 pmol). Intravenous pretreatment with naloxone (0.5 mg/kg body weight) diminished the inhibitory action of leumorphin (60 pmol) on vasopressin secretion. Moreover, naloxone (0.5 mg/kg body weight) prolonged the vasopressin secretion induced by intracerebroventricular injection of angiotensin II (100 pmol). These results indicate that leumorphin possesses a potent inhibitory effect on vasopressin secretion and that, alone or in combination with other endogenous opioid peptides, it plays an important role in the control of vasopressin secretion.
Hypertension 1988 Feb
PMID:Implication of leumorphin in inhibitory control of vasopressin secretion in conscious rats. 334 67

The tissue contents of catecholamines (CAs) and methionine-enkephalin-like immunoreactivity (Met-enk) were examined in 8 patients with phaeochromocytomas (Phs). In 6, Ph cells were cultured, and the modes of secretion of CAs and Met-enk were examined. Tissue contents of CAs and Met-enk varied from patient to patient, but larger amounts of Met-enk were found in medullary Phs than extramedullary ones, regardless of the secreting CA type. Three patients with extramedullary Phs had clinically showed a sustained hypertension, whereas five with medullary Phs were normotensive or had occasional paroxysmal hypertension. Nicotine (10(-7) M to 10(-4) M) stimulated simultaneous secretion of CAs and Met-enk from the cultured human Ph cells. Met-enk, however, was not secreted in proportion to either epinephrine (E), norepinephrine (NE) or total CAs (E + NE). Met-enk, FK33-824 (FK) (Met-enkephalin analogue), and dynorphin 1-13 (Dyn) significantly suppressed the secretion of CA evoked by 10(-5) M nicotine. The 50% inhibitory concentrations (IC50) of Met-enk, FK, and Dyn were 5 X 10(-6) M, 9.9 X 10(-5) M, and 9.0 X 10(-8) M, respectively, in one patient and 9.0 X 10(-6) M, 1.5 X 10(-7) M, and 1.4 X 10(-7) M in another. In one patient, 10(-5) M naloxone inhibited the CA secretion evoked by 10(-5) M nicotine and did not reverse the 10(-5) M FK-induced suppression of CA secretion in the presence of 10(-5) M nicotine. These results suggest that human Phs may be heterogeneous with regard to storage and secretion of CAs and opioid peptides.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Catecholamines and opioid peptides in human phaeochromocytomas. 378 13

A 42-year-old female with clinical and endocrine indications of Cushing's syndrome, as well as periodic hypertension and increased urinary catecholamines and their metabolites, benefitted from removal of a pheochromocytoma. Adrenocortical hyperplasia was present. Electron microscopy showed catecholamine-type granules in the tumor cells; in addition, immunoreactive ACTH, leu-enkephalin, somatostatin, and serotonin were identified. Such studies were performed for the first time in this unusual condition.
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PMID:Pheochromocytoma producing immunoreactive ACTH with Cushing's syndrome. 609 99

The putative transmitters, enkephalins and substance P, and their binding sites have been identified in the nucleus of the solitary tract. Their role in the modulation of baroreceptor reflex activity is the subject of this study in the rabbit. A stable decarboxy analog of leu-enkephalin, RX 783016, which has mu receptor specificity, was used to attenuate the baroreflex sensitivity to intravenous phenylephrine. RX 783016, 50 micrograms/kg intracisternally, did not alter resting heart rate of blood pressure. Intravenous administration of the opiate receptor antagonist, naloxone, prevented the effects of RX 783016. Naloxone given alone significantly increased reflex sensitivity. Substance P given intracisternally in low doses (1 to 10 ng/kg) caused a dose-dependent pressor response, which was reduced by pretreatment with morphine and enhanced by naloxone. Bilateral sinoaortic denervation also enhanced the pressor response to substance P, but after deafferentation, naloxone had no further effect. It is proposed that enkephalin-containing neurons, acting through mu receptors, and substance P neurons influence baroreceptor reflex activity by modulating respectively the primary and second order neurons of the baroreceptor reflex.
Hypertension
PMID:Opiate analogs, substance P, and baroreceptor reflexes in the rabbit. 616 14

The effect of dynorphin A-(1-13) (Dyn A-(1-13)) on [3H]norepinephrine ([3H]NE) uptake was examined in cardiac synaptosomal-mitochondrial fractions of control rats (Wistar, WR; Wistar-Kyoto, WKY) and spontaneously hypertensive rats (SHR). In adult WR, Dyn A-(1-13) caused naloxone-insensitive dose-dependent inhibition of [3H]NE uptake with an IC50 of 4.0 microM. The nonopioid Dyn A fragments Dyn A-(2-13) and Dyn A-(6-10) displayed 89 and 11% of the potency of Dyn A-(1-13), respectively, whereas Dyn A-(1-8), Leu-enkephalin, and the selective opioid agonists [D-Ala2, N-MePhe4, Glyol5]enkephalin (DAGO, mu), [D-Ser2, Thr6]Leu-enkephalin (DSLET, delta), and U-50488H (kappa) were inactive. The relative potency of various analogues and fragments of Dyn A in inhibiting [3H]NE uptake correlated well (r = 0.96) with their potency in inhibiting binding of [3H]Dyn A-(1-13) to nonopioid sites on cardiac membrane preparations. Dyn A-(1-13) showed the same potency in inhibiting [3H]NE uptake in prehypertensive (4-week-old) SHR as in age-matched WR and WKY. However, at ages 8 and 16 weeks Dyn A-(1-13) was twice as potent in SHR as in WR and WKY. The increased inhibitory potency of Dyn A-(1-13) in 8-week-old SHR was accompanied by a 1.3-fold increase in number of cardiac nonopioid [3H]Dyn A-(1-13) binding sites. Dyn A and related peptides inhibit [3H]NE uptake by cardiac synaptosomes by a nonopioid mechanism. The possible involvement of such a mechanism in development of hypertension in SHR is discussed.
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PMID:Inhibitory effects of dynorphin-A on norepinephrine uptake by cardiac synaptosomal-mitochondrial fractions. 759 17

Dentate granule cells can be selectively destroyed by intrahippocampal injections of colchicine. This study evaluates the consequences of granule cell destruction on blood pressure regulation in the normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR). Bilateral destruction of dentate granule cells at 6 weeks of age produced a significant increase in blood pressure in the WKY that lasted for approximately 3 weeks, and a biphasic effect (increase then decrease) in the SHR that resulted in a significant hypotensive period that persisted for 6 weeks. Granule cell destruction at 11 weeks produced a maximal hypertension in the SHR that preceded age-matched controls by 4 weeks, but produced only a small transient increase in WKY blood pressure. Dentate granule cells are the exclusive source of prodynorphin-derived peptides in the hippocampal formation and their synthesis is regulated by glucocorticoids. Evidence suggests glucocorticoids may be involved in the regulation of blood pressure and hypertension. We determined that chronic high levels of corticosterone significantly reduced hippocampal dynorphin B levels in normotensive Sprague-Dawley rats. In addition, we confirmed that naive SHRs also contain significantly lower levels of hippocampal dynorphin B. These results suggest (i) that dentate granule cells represent a discrete neural site that may exert a tonic inhibitory influence on blood pressure, (ii) that dentate granule cells are not required for the full expression of hypertension in the SHR, and (iii) that chronic high levels of corticosterone can reduce dynorphin B levels in the dentate granule cells of normotensive rats.
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PMID:Dentate granule cells as a central cardioregulatory site in the rat. 782 May 90

Previous studies by us established that dynorphin A-(1-8) concentration in the hippocampal formation of spontaneously hypertensive rat (SHR) brain was much less than in the hippocampus of normotensive controls. The connection between low dynorphins and SHR hypertension was unclear. The object of the present study was to determine (1) whether microinjections of dynorphin A-(1-8) into the hippocampus of anesthetized SHR would produce centrally mediated effects on arterial pressure and heart rate and (2) whether these responses would differ qualitatively or quantitatively from those elicited in normotensive Wistar-Kyoto (WKY) or Sprague-Dawley rats. A statistically significant elevation of arterial pressure was observed in SHR at 8, 12 and 16 weeks compared to WKY and Sprague-Dawley controls at similar ages. There were no significant changes in heart rate of SHR compared to WKY and Sprague-Dawley rats. Intra-hippocampal dynorphin A-(1-8) caused a dose-dependent (0.05, 0.5, 5.0 and 50.0 nmol) hypotension and bradycardia in all strains, and ages but the responses were quantitatively larger in SHR than in the normotensive strains. Nor-binaltorphimine, a selective antagonist for kappa-opioid receptor, pretreated into the hippocampus caused a significant blockade of the dynorphin A-(1-8) responses in all strains. The results established that (1) intra-hippocampal dynorphin A-(1-8) lowered the arterial pressure and heart rate by a central mechanism, in all strains, at all ages tested and (2) the responses were quantitatively greater in SHR than in WKY and Sprague-Dawley strains. The responses appear to involve activation of a kappa receptor in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiovascular responses to intra-hippocampal dynorphin A-(1-8) in spontaneously hypertensive rats. 791 47

A significantly lower level of preprodynorphin mRNA hybridization signal was found in hippocampal dentate granule cells of spontaneously hypertensive rats at 4 and 16 weeks old, before and after hypertension development respectively, when compared with preprodynorphin (PPD) mRNA level in the hippocampus of age-matched Wistar-Kyoto rats. The possible implications of disturbed PPD mRNA and dynorphin expression in the hippocampus are discussed with regard to pathophysiology of hypertension and central control of cardiovascular function.
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PMID:A deficit in preprodynorphin mRNA expression in hippocampus of spontaneously hypertensive rats. 791 41

1. A comparison of the effects of various opioid peptides on the heart rates of self-paced right atria was made, as taken from spontaneously hypertensive (SHR), Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats at 4, 8, 12 and 16 weeks of age. 2. Beta-endorphin, dynorphin, met-enkephalin, DAGO and DADLE slightly decreased the spontaneously beating rate of all rat strains and ages, at 0.1 microM. Leu-enkephalin at 0.2 microM increased the spontaneous beating rate of SHR atria, but not that of atria from normotensive strains. 3. SHR atria were somewhat more sensitive than WKY atria to norepinephrine (NE)-induced positive chronotropy, but the differences were not statistically significant. 4. In the presence of mu, delta or kappa opioid receptor agonists, SHR atrial sensitivity to NE-induced chronotropy was enhanced at all ages studied. By contrast, NE chronotropy was not significantly altered by the opioids in normotensive rat atria. 5. Based on the above results, all the three major opioid receptor subtypes (mu, delta and kappa) appear to be present in rat atria but the function of these receptors appears to be greater in SHR than in WKY and SD atria. 6. The results suggest a possible involvement of altered opioid responsiveness in atria during hypertension development in SHR but the nature of this involvement appears to be complex and is not readily understandable on the basis of the present study.
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PMID:Possible opioid receptor function changes in isolated atria of the spontaneously hypertensive rat. 811 24

To investigate the involvement of endogenous opioids in acute increases in blood pressure and their functional relationship with atrial natriuretic factor and endothelin-1, we assessed plasma levels of beta-endorphin, met-enkephalin, dynorphin B, catecholamines, atrial natriuretic factor, and endothelin-1 before and after administration of the opioid antagonist naloxone hydrochloride (8 mg i.v.) in 28 hypertensive patients with a stress-induced acute increase in blood pressure. Ten patients with established mild or moderate essential hypertension and 10 normotensive subjects served as control groups. Opioids, atrial natriuretic factor, and endothelin-I were radioimmunoassayed after chromatographic preextraction; catecholamines were determined by high-performance liquid chromatography with electrochemical detection. Patients with an acute increase in blood pressure (systolic, 203.2 +/- 2.2 mm Hg; diastolic, 108.4 +/- 1.3) had plasma opioid, catecholamine, and atrial natriuretic factor levels significantly (P < .01) higher than hypertensive control patients (systolic pressure, 176.4 +/- 1.0 mm Hg; diastolic, 100.0 +/- 1.4), who had a hormonal pattern similar to that of normotensive subjects (systolic pressure, 123.2 +/- 1.5 mm Hg; diastolic, 75.0 +/- 2.0). Endothelin-1 did not differ in any group. In patients with an acute increase in blood pressure, naloxone significantly (P < .01) reduced blood pressure, heart rate, opioids, catecholamines, and atrial natriuretic factor 10 minutes after administration. Naloxone effects on blood pressure, heart rate, opioids, and catecholamines wore off within 20 minutes. In control groups, naloxone failed to modify any of the considered parameters. Our findings suggest that pressor effects of opioid peptides mediated by the autonomic nervous system during stress-induced acute episodes of blood pressure increase in hypertensive patients.
Hypertension 1997 Jan
PMID:Pressor effects of endogenous opioid system during acute episodes of blood pressure increases in hypertensive patients. 903 88


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