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

The relationship of age-dependent changes in concentrations of various opioid peptides in the brain and pituitary to the development of hypertension was studied in the spontaneously hypertensive rat (SHR). Normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats served as controls. Opioids determined were dynorphin A (1-8) [DN-A(1-8)], beta-endorphin (BE) and Met-enkephalin (ME). Three approaches were used: (1) temporal correlations of opioid concentrations with the onset of hypertension in 4-, 8-, 12- and 16-week-old rats; (2) study of opioid changes when hypertension development was prevented with antihypertensive drugs and (3) determination of possible opioid peptide changes in another rat model of hypertension, the deoxycorticosterone acetate (DOCA) + salt model. Opioid peptide concentration differences (SHR/WKY) found were as follows. There were much lower DN-A(1-8) levels in the SHR hippocampus and hypothalamus at all ages studied. At 12 and 16 weeks, coincidently with the onset of hypertension, lower levels of BE were found in the anterior lobe of the pituitary, but there were higher BE and ME levels found in the neurointermediate lobe (NIL). Prevention of hypertension in SHR by 8 weeks of oral therapy with guanethidine and hydralazine reversed the BE and ME changes in the NIL but not in the anterior lobe. There were no brain or pituitary changes in opioid peptide concentrations associated with DOCA-salt hypertension. The results are interpreted as supporting a role for altered concentrations of brain and pituitary opioids in the genesis of SHR hypertension.
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PMID:Age-related changes in opioid peptide concentrations in brain and pituitary of spontaneously hypertensive rats. Effect of antihypertensive drugs and comparison with deoxycorticosterone acetate and salt hypertension. 135 4

Dynorphin receptor binding sites in hippocampal membrane preparations were assessed in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at 4, 8, 12 and 16 weeks of age. At 4 weeks of age, before hypertension is manifested, SHRs had significantly more hippocampal dynorphin receptor binding sites than WKY controls. At 8, 12 and 16 weeks of age, however, when hypertension is seen, SHRs showed significantly fewer hippocampal binding sites than WKY rats. No receptor affinity changes for dynorphin were seen between the two strains of rats at any age. These results suggest that hippocampal receptor changes involving the opioid system may play a role in the central component of blood pressure control.
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PMID:Dynorphin receptor changes in hippocampus of the spontaneously hypertensive rat. 135 77

Primary paraganglioma arises infrequently in the urinary bladder. We present the clinicopathologic, immunohistochemical, ultrastructural, and DNA flow cytometric findings in three cases (one man and two women). Ages at diagnosis were 19, 35, and 45 years. One female presented with paroxysmal headaches and hypertension that followed urination; the remaining two patients presented with hematuria. Immunohistochemical studies revealed positive reactivity for chromogranin (three patients), met-enkephalin (three), leu-enkephalin (three), vasoactive intestinal polypeptide (two), serotonin (one), and S-100 protein (one; sustentacular cells only). Neurosecretory granules were identified in all cases; in the patient with hypertension, the granules were small with eccentric cores similar to those of adrenal pheochromocytomas. A nondiploid DNA flow cytometric pattern was present in all three patients, an aneuploid pattern was present in two, and a tetraploid pattern was present in one. After diagnosis, one patient was alive without progression at 7 years, one died of an uncertain cause at 5 years, and one suffered multiple recurrences over a 24-year period before developing metastatic disease. While the presence of aneuploidy has been shown to be a predictor of malignant behavior in adrenal pheochromocytomas, our study illustrates that DNA ploidy cannot be used as a diagnostic criterion for malignancy in urinary bladder paraganglioma.
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PMID:Paraganglioma of the urinary bladder: immunohistochemical, ultrastructural, and DNA flow cytometric studies. 174 2

In order to investigate the pathophysiological role of heart dynorphin-A (Dyn-A) in genetic hypertension, immunoreactive (ir)-Dyn-A was measured in heart extracts of spontaneously hypertensive rats (SHR) and compared with that of age matched Wistar (WR) and Wistar Kyoto (WKY) rats. Heart ir-Dyn-A contents in 8 week-old WK (84 fmol/g tissue) were not significantly different from those of age matched WKY (109 fmol/g tissue). In control WKY, the levels of ir-Dyn-A did not significantly vary with the age (from 109 to 117 fmol/g) except in 16 week-old animals which displayed a significant increase (238 fmol/g tissue) compared to younger animals. In SHR, the heart content of ir-Dyn-A displayed a 6.5 fold increase at 8 weeks compared to age matched WKY. Older SHR showed a return of their heart ir-Dyn-A content to control (12 week-old) or below control values (16 week-old; 121 compared with 238 fmol/g tissue in WKY). Heart ir-Dyn-A in WKY and SHR eluted as a single peak on mu-Bondapak HPLC, corresponding with the retention time of synthetic Dyn-A. A local function for cardiac ir-Dyn-A is suggested by the presence in heart membrane preparations of a high affinity binding site for the kappa selective opioid ligand, [3H]U-69593, with KD of 6.4 (WKY) and 8.5 (SHR) nM and Bmax of 3.7 (WKY) and 3.6 (SHR) pmol/g protein. The alterations in the levels of cardiac ir-Dyn-A during the development of hypertension in SHR were analyzed in regard with the reported effects of Dyn-related peptides on heart natriuretic and sympathetic functions.
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PMID:Alterations of heart dynorphin-A in the development of spontaneously hypertensive rats. 197 Jan 35

In this study the possible role of hippocampal dynorphin in the development of hypertension in spontaneously hypertensive rats (SHR) was investigated by determining dynorphin A (1-8) (DN A (1-8] levels in hippocampus in 16 week old SRH, Wistar Kyoto (WKY) controls and SHR treated with antihypertensive drugs as well as DOCA-salt hypertensive Sprague Dawley (SD) rats, using radioimmunoassay (RIA). We found that DN A (1-8) was decreased significantly in both dorsal (-68%) and ventral (-58%) hippocampus in SHR compared with WKY rats. Treatment with hydralazine and guanethidine (25 mg/kg/24 hr of each drug in drinking water) for 8 weeks to prevent the development of hypertension in young SHR had no effect on this low hippocampal dynorphin level. We failed to find significant changes in hippocampal DN A (1-8) level in DOCA-salt hypertensive rats. The low level of hippocampal dynorphin existed before the development of hypertension in 6 day neonatal SHR (-73%). Hippocampal Met-enkephalin was unchanged in all experimental groups except for a slight decrease in neonatal SHR. The results establish a genetic difference in the hippocampal dynorphin system of SHR compared with WKY, the significance of which, for the development of hypertension, remains to be investigated.
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PMID:Hippocampal levels of dynorphin A (1-8) in neonatal and 16-week-old spontaneously hypertensive rats: comparisons with DOCA-salt hypertension. 198 62

The effect of intracisternal pretreatment with opiate antagonists or antisera against various opioid peptides on the hypotension and bradycardia induced by cumulative intracisternal administration of clonidine (0.02-2.5 microgram) was studied in conscious Wistar-Kyoto rats and in spontaneously hypertensive rats. No effect of any pretreatment on basal values of blood pressure and heart rate was detected in either of these strains. In spontaneously hypertensive rats intracisternal pretreatment with naltrexone resulted in a dose-dependent inhibition of clonidine-induced hypotension and bradycardia. DL-naloxone also antagonized the hypotension but not influence the hypotensive and bradycardic response to clonidine. In Wistar-Kyoto rats naltrexone and the beta-endorphin antiserum B4 failed to affect the cardiovascular effects of clonidine. B4 and an antiserum against dynorphin(1-13) inhibited clonidine-induced hypotension in spontaneously hypertensive rats, whereas a [Met5]enkephalin antiserum had no effect. Use of antisera specifically recognizing the C-terminus of beta-, alpha-, and gamma-endorphin, respectively, revealed that only the beta-endorphin antiserum inhibited the fall in blood pressure in spontaneously hypertensive rats after cumulative administration of clonidine. None of the antisera used affected clonidine-induced bradycardia. These results indicate that activation of stereospecific opiate receptors in spontaneously hypertensive, but not in Wistar-Kyoto rats, plays a role in the central hypotensive effect of clonidine. beta-Endorphin(1-31) and dynorphin(1-13) might be the endogenous ligands for these receptors.
Hypertension 1989 Jan
PMID:Possible involvement of brain opioid peptides in clonidine-induced hypotension in spontaneously hypertensive rats. 253 2

1. The effects of intracerebroventricular (i.c.v.) and intracisternal (i.c.) administration of a range of doses (0.01, 0.1 and 1.0 nmol kg-1) of specific mu- delta- and kappa-opioid agonists on cardiovascular and respiratory function and on plasma catecholamines have been studied in conscious rabbits. The distribution of mu- delta- and kappa-opioid receptors was localized in rabbit brain by in vitro autoradiography. 2. The mu-agonist [D-Ala2, MePhe4-Gly5-ol]enkephalin (DAGOL) given i.c.v. caused a large rise in plasma noradrenaline and adrenaline, hypertension accompanied by an initial bradycardia followed by tachycardia, respiratory depression and sedation. After i.c. administration there were similar changes in heart rate (HR) and respiration, but no significant changes in mean arterial pressure (MAP) or plasma catecholamines. 3. The delta-agonist [D-Pen2.5]enkephalin (DPDPE) increased MAP and HR after both i.c.v. and i.c. administration, caused a small increase in noradrenaline but had no effect on adrenaline and did not alter respiration rate or blood gases. After i.c.v. DPDPE the rabbits became more alert and active. 4. The kappa-agonist U69593 given i.c.v. or i.c. had no effect on MAP or HR. After i.c.v. U69593, PaCO2 fell, but there were no other respiratory effects. The responses to dynorphin 1-13, an endogenous kappa-agonist, were similar to those of U69593. 5. The opioid antagonist naloxone (30 nmol kg-1) given intravenously (i.v.) blocked the effects of i.c.v. DAGOL (1 nmol kg-1). A 100 fold higher dose of i.v. naloxone (3 mumol kg-1) was required to abolish the effects of i.c.v. DPDPE (1 nmol kg-1). 6. Autoradiographic studies demonstrated a high density of mu- and delta-opioid receptors in hypothalamic sites. In the brainstem mu-receptors were demonstrated in the nucleus tractus solitarius (NTS) and delta-receptors in the dorsal motor nucleus of the vagus. kappa-Receptors were not detected in either the hypothalamus or brainstem. 7. These findings demonstrate that DAGOL increases sympatho-adrenal outflow, probably by stimulation of hypothalamic mu-receptors. The effects on HR are probably partly through a baroreflex and partly through an action of DAGOL on mu-receptors in the dorsal motor nucleus of the vagus. DPDPE probably acts on delta-receptors in the NTS to increase MAP and HR. Respiratory depression resulted from stimulation of mu-receptors in the brainstem with no evidence of delta- or kappa-receptors being involved.
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PMID:Differential cardiovascular and respiratory responses to central administration of selective opioid agonists in conscious rabbits: correlation with receptor distribution. 255 6

Dynorphin A (1-8)-like immunoreactivity (DN-LI A(1-8] was determined by radioimmunoassay in the brains of age matched spontaneously hypertensive rats (SHR) and two normotensive control groups consisting of Wistar-Kyoto (WKY) and Sprague-Dawley (SD) strain rats. A significantly lower DN-LI A(1-8) was found in the hippocampus and hypothalamus of the SHR compared with the WKY groups. DN-LI A(1-8) was 24% of control WKY levels in hippocampus and 79% of that in WKY hypothalamus at 16 weeks. Similar lower levels of DN-LI A(1-8) were also observed in SHR at 4, 8, and 12 weeks during the development of hypertension when compared with both WKY and SD groups. We failed to find significant differences in brain stem DN levels between the groups. The relationship between the low hippocampal dynorphin levels in SHR and the hypertension is problematical because the differences were present before (4 wks), during (8 and 12 wks) and after (16 wks) its development.
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PMID:A low hippocampal dynorphin A (1-8) immunoreactivity in spontaneously hypertensive rats. 256 57

The occurrence and distribution of peptide-containing nerve fibers to the cerebral circulation are described. Immunocytochemical studies have revealed that cerebral blood vessels are invested with nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP). In addition, there are studies reporting the occurrence of putative neurotransmitters such as cholecystokinin, dynorphin B, galanin, gastrin releasing peptide, vasopressin, neurotensin, and somatostatin. The nerves occur as a longitudinally oriented network around large cerebral arteries. There is often a richer supply of nerve fibers around arteries than veins. The origin of these nerve fibers has been studied by retrograde tracing and denervation experiments. These techniques, in combination with immunocytochemistry, have revealed a rather extensive innervation pattern. Several ganglia, such as the superior cervical ganglion, the sphenopalatine ganglion, the otic ganglion, and small local ganglia at the base of the skull, contribute to the innervation. Sensory fibers seem to derive from the trigeminal ganglion, the jugular-nodose ganglionic complex, and from dorsal root ganglia at level C2. The noradrenergic and most of the NPY fibers derive from the superior cervical ganglion. A minor population of the NPY-containing fibers contains VIP instead of NA and emanates from the sphenopalatine ganglion. The cholinergic and the VIP-containing fibers derive from the sphenopalatine ganglion, the otic ganglion, and from small local ganglia at the base of the skull. Most of the SP-, NKA-, and CGRP-containing fibers derive from the trigeminal ganglion. Minor contributions may emanate from the jugular-nodose ganglionic complex and from the spinal dorsal root ganglia. NPY is a potent vasoconstrictor in vitro and in situ. VIP, PHI, SP, NKA, and CGRP act via different mechanisms to induce cerebrovascular dilatation. The sympathetic, the parasympathetic, and the sensory systems appear to be involved in modulating cerebrovascular tone in hypertension and in conditions of threatening vasoconstriction, e.g., subarachnoid hemorrhage and migraine.
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PMID:Neuropeptides in the cerebral circulation. 270 77

Though acute nicotine administration results in increased blood pressure and heart rate, previous work has shown that chronic nicotine treatment does not result in significant hypertension. In fact, surprisingly it has been shown to produce hypotension. We performed the present experiments to further analyze the effects of chronic nicotine treatment. In untreated dogs (n = 7) under pentobarbital anesthesia (with adrenal hormone release measured directly by cannulation of the adrenolumbar veins) cumulative nicotine infusions (1-24 micrograms/kg/min i.v.) caused dose-dependent release of epinephrine (from 3.0 +/- 0.7 to 111 +/- 30 micrograms/kg/min) and norepinephrine (from 0.4 +/- 0.1 to 11.2 +/- 3.1). However, significant release of leu-enkephalin and met-enkephalin immunoreactivity was observed only with the highest nicotine infusion (24 micrograms/kg/min). In untreated conscious dogs (n = 12), nicotine test infusions (3 and 10 micrograms/kg/min), 15 min, yielded smoking relevant plasma nicotine levels and augmented heart rate, mean arterial pressure, plasma catecholamine levels, and adrenal epinephrine release. Plasma-enkephalin immunoreactivities were only marginally elevated with the higher nicotine test infusion. Chronic nicotine treatment (1.5 micrograms/kg/min s.c. for 5 weeks, n = 7), only transiently (first 1-2 weeks) augmented mean arterial pressure, heart rate, and epinephrine release, but during the plateau phase of treatment, hemodynamics and catecholamine parameters were identical to the pretreatment period. Acute responses of hemodynamics and catecholamines to nicotine test infusions declined progressively during chronic treatment, but the time course of this attenuation seemed not related to the reversal of the transient hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sympathoadrenal activity and sympathoinhibitory hormones during acute and chronic nicotine application in dogs. 297 78


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