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

In the past, treatment of hypertension frequently involved bed rest, a procedure known to reduce the activity of the sympathetic nervous system (SNS), generally implied in the defense reaction of the organism that is elicited by salient, environmental stimuli. Evidence is presented that brain noradrenaline (NA) neurons in the locus coeruleus (LC) and major parts of the SNS respond by burst activation in concert to stressful stimuli implying novelty or fear. alpha-Adrenoceptor agonists such as clonidine exert a powerful inhibitory action on both LC neurons and the SNS, thereby reducing the impact of salient environmental events on the organism. Our most recent data suggest that clonidine can reduce burst firing of catecholamine neurons and cause a more regular firing pattern. This may explain reduced release of coexisting neuropeptides such as neuropeptide Y (NPY) in sympathetic nerves, which we have observed following clonidine treatment, since such neuropeptides are particularly effectively released in burst sequences. Coexisting neuropeptides have been thought to be involved in learning processes and the encoding of short-term memory. Consequently, treatment with alpha 2-adrenoceptor agonists may imply reduced engraving of stressful events, conveyed by central and peripheral catecholamine neurons.
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PMID:Stress, central neurotransmitters, and the mechanism of action of alpha 2-adrenoceptor agonists. 245 97

The effect of the intrathecal administration of neuropeptide Y (NPY) on blood pressure and heart rate of anesthetized normotensive and hypertensive rats was studied. Neuropeptide Y was observed to produce a decrease in the blood pressure of Sprague-Dawley, Wistar Kyoto (WKY), DOCA-salt, and DOCA-sham control rats. The maximum percent decrease in blood pressure of Sprague-Dawley rats was 12.8 and 15.2% in response to 0.1 and 1.0 nmol NPY, respectively. Similar changes in heart rate were observed. The depressor effect of intrathecal NPY was attenuated by prior treatment with yohimbine and propranolol but not prazosin. The depressor effect of intrathecal NPY observed in normotensive and DOCA-salt hypertensive rats was not seen in the spontaneously hypertensive rat (SHR). The studies extend to the spinal cord the list of regions and tissues where NPY can produce physiological effects. It is concluded that the effects of NPY are closely associated with sympathetic preganglionic neurons in the spinal cord that the depressor effect of NPY involves alpha 2 and beta adrenoceptors, and that a loss of the depressor effect of NPY may contribute to the development or maintenance of hypertension in the SHR.
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PMID:Alterations in blood pressure of normotensive and hypertensive rats following intrathecal injections of neuropeptide Y. 246 49

Noradrenergic neurons in the locus ceruleus contain neuropeptide Y and galanin, which project to the hypothalamic region. We have investigated the regulatory mechanisms of these peptides on norepinephrine release in rat hypothalamic slices in vitro. Neuropeptide Y and galanin significantly inhibited the stimulation-evoked [3H]norepinephrine release in a dose-dependent manner (1 Hz: S2/S1 ratio (mean +/- SEM), control 0.947 +/- 0.040, n = 11, neuropeptide Y 1 x 10(-8) M 0.509 +/- 0.013, n = 8, p less than 0.01, neuropeptide Y 1 x 10(-7) M 0.283 +/- 0.021, n = 8, p less than 0.01; galanin 1 x 10(-7) M 0.448 +/- 0.026, n = 8, p less than 0.01, galanin 1 x 10(-6) M 0.261 +/- 0.023, n = 8, p less than 0.01). The inhibition of norepinephrine release by the alpha-2 agonist UK 14,304 was potentiated by neuropeptide Y and galanin. The blockade of the alpha 2-adrenergic receptors by RX 781094 diminished the inhibitory effects of neuropeptide Y and galanin on norepinephrine release. Pretreatment of hypothalamic slices with islet activating protein (a toxin that interferes with the coupling of inhibitory receptors to adenylate cyclase) attenuated the suppression of norepinephrine release by UK 14,304, neuropeptide Y, and galanin. These results support the idea that neuropeptide Y and galanin are involved in the regulation of central adrenergic transmission partially mediated by alpha 2-adrenergic receptors and islet-activating protein-sensitive guanosine triphosphate-binding proteins in rat hypothalamus.
Hypertension 1989 Jul
PMID:Neuropeptide Y and galanin in norepinephrine release in hypothalamic slices. 247 59

Perivascular innervation of the mesenteric arteries of 7-week-old and 6-month-old spontaneously hypertensive rats and normotensive Wistar-Kyoto rats was examined. The densities of neuropeptide Y-containing nerve fibers and adrenergic nerve fibers were increased in the distal regions of mesenteric arteries of spontaneously hypertensive rats as compared with findings in Wistar-Kyoto rats. However, the densities of cholinergic nerve fibers, vasoactive intestinal polypeptide-containing, and substance P-containing nerve fibers in the mesenteric arteries of the spontaneously hypertensive rats were unchanged in comparison with findings in the Wistar-Kyoto rats. Thus, not only adrenergic nerve fibers but also neuropeptide Y-containing nerve fibers may play an important role in the development and maintenance of hypertension in spontaneously hypertensive rats.
Hypertension 1989 Dec
PMID:Perivascular innervation of the mesenteric artery in spontaneously hypertensive rats. 247 2

Secretory components of the adrenal medulla were compared in normotensive Wistar-Kyoto (WKY) rats and in stroke-prone spontaneously hypertensive rats (SHRSP) at both 4 and 12 months of age. Noradrenaline, adrenaline, dopamine, neuropeptide Y, and chromogranins A and B were significantly higher in adrenal glands of SHRSP than those of WKY rats at 4 months. At 12 months, the levels of these components in SHRSP had increased even more (about 200% in WKY rats). There was no change in the relative composition of the adrenal "secretory cocktail." Neither the chromogranin A/chromogranin B ratio nor their apparent proteolytic processing in chromaffin granules differed between SHRSP or WKY rats. The lack of a significant change in membrane-bound cytochrome b561 and the small increase in dopamine beta-hydroxylase suggest that the higher levels of secretory components in SHRSP are not simply caused by an increase in the number of chromaffin granules, but possibly by a selective increase in the secretory content of these organelles providing a larger package for quantal release by exocytosis. This may be relevant for the elevation of blood pressure in this strain. The immunological methods described in this paper allow for the first time a determination of the secretory quantal levels in catecholamine storage. This should be useful for further studies in hypertensive models.
Hypertension 1989 May
PMID:An increased pool of secretory hormones and peptides in adrenal medulla of stroke-prone spontaneously hypertensive rats. 256 78

Morbid obesity is a major health problem in this country and throughout the world. In addition to its social stigma (in the western world), obesity exacerbates several disease states such as diabetes, hypertension, cardiac disease and restrictive lung disease. When effective medical treatment of obesity becomes available, it will depend in part upon understanding the physiologic factors that control satiety. This review summarizes the information available on brain and gut control mechanisms of satiety. Brain nuclei located in the lateral hypothalamus, ventromedial hypothalamus, and other paraventricular areas are the sites of action for potent neuropeptides, such as cholecystokinin (CCK) and neuropeptide Y, that appear to regulate feeding. Exogenous CCK has been used clinically to decrease meal size in obese patients. The sites of the satiety cascade that are most often manipulated are the gastric and intestinal phases. Physiologic gastric distension is a potent inhibitor of feeding, whereas the intermeal interval may be regulated by intestinal signals released by food in the gut. Jejunal-ileal bypass has fallen from favor and has been replaced by gastric restrictive procedures that create a small proximal gastric pouch that empties into the small bowel (gastric bypass) or the distal stomach (gastroplasty). These operations rely partially on their ability to produce gastric distension in the proximal gastric pouch at an early stage during a meal. Thus, failure results if the pouch compensates by distending or if the stoma widens with subsequent loss of slow emptying. Improved medical and surgical treatment will be designed to intervene at specific sites of the satiety cascade as knowledge of the physiologic control mechanisms of satiety increases.
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PMID:Physiologic approaches to the control of obesity. 229 39

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

High plasma concentrations of neuropeptide Y (NPY) were found in a patient with bilateral adrenal phaeochromocytomas and medullary thyroid carcinoma associated with MEN IIa (32 pmol/l, normal less than 3.5 pmol/l). Both adrenal tumours contained and secreted NPY. Manipulation at operation produced a remarkable increase in plasma NPY concentrations (peak = 1631 pmol/l) coinciding with increases in plasma levels of catecholamines and arterial pressure. NPY was also shown to be present in thyroid tumour tissue: the concentration of NPY in tumour was 50-fold higher (0.9 nmol/g vs 0.004 nmol/g) than in adjacent normal thyroid tissue. It is possible that NPY from some phaeochromocytomas may contribute to hypertension during surgery.
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PMID:Neuropeptide Y in multiple endocrine neoplasia: release during surgery for phaeochromocytoma. 287 55

Although the majority of extraadrenal paragangliomas are nonfunctional, some of these tumors are associated with hormone production and clinical symptoms, notably hypertension. The authors have investigated 22 paragangliomas, five of which were diagnosed as clinically functional in a light microscopic immunocytochemical and electron microscopic study (nine cases). Histologically, all the paragangliomas exhibited similar features, with a "Zellballen" pattern of polygonal cells. All 22 cases were strongly immunoreactive to protein gene product 9.5 (PGP 9.5) antisera and moderately reactive to antineuron-specific enolase (NSE) sera. Ten cases (five functional) were focally immunoreactive to antichromogranin sera. Seven cases (four functional) were immunoreactive to neuropeptide Y and enkephalin antisera, and six (five functional) to tyrosine hydroxylase antisera. The clinically functional tumors expressed at least two of the antigens, enkephalin, neuropeptide Y, or tyrosine hydroxylase, whereas none of the 17 nonfunctional possessed more than one of these. Electron microscopic study revealed cells from all the nine cases studied to contain secretory granules. Granule sizes ranged from 100 to 280 nm and the morphologic examination of the secretory granules generally showed a dense core with a membrane-bound halo of variable size. Secretory granules were observed in the five functional cases and these were larger (220-280 nm) than those seen in the nonfunctional tumor cells (100-180 nm). Also, tumor cells from the functional cases contained numerous dilated mitochondrial profiles.
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PMID:Extraadrenal paragangliomas. An immunocytochemical and ultrastructural report. 288 26

Studies of the roles played by neurotransmitters in the development of hypertension in the spontaneously hypertensive (SHR) rat are complicated by the presence of genetic differences between SHR and normotensive control rats, which are not related to differences in blood pressure. One approach that may be used in an attempt to overcome this difficulty is to study the manner in which neurotransmitter and metabolite levels change with age, and to relate these changes to alterations in blood pressure with ageing. Noradrenaline (NA) levels in the brainstem and spinal cord of SHR and Wistar Kyoto rats fell with age, while 3,4-dihydroxyphenylethyleneglycol (DHPG) levels (a neuronal metabolite of noradrenaline) remained constant. Similar changes were seen when NA and DHPG levels were measured in the discrete brainstem A1, A2, and C2 region, and when adrenaline, NA, and DHPG levels were examined in the C1 region. Differences in age-related changes of neuropeptide Y (NPY) levels were also found in the ventromedial nucleus of the hypothalamus and the locus coeruleus, and of beta-endorphin in the anterior hypothalamic nucleus, the paragigantocellular nucleus of the brainstem, and the locus coeruleus. These changes may indicate either a progressive increase in the activity of neurons in the sympathoexcitatory C1 region or a progressive reduction in the activity of vasodepressor A1, A2, and C2 regions with ageing, or both. However, changes in catecholamines and metabolites with age were similar in both strains and therefore cannot readily explain the more rapid rise in blood pressure with ageing in SHR rats.
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PMID:Neurotransmitters and neuropeptides in blood pressure regulation in the spontaneously hypertensive rat. 296 19


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