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)

In the present study, the mean arterial pressures (MAP) and heart rates (HR) were measured in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) that had received a 10-day continuous subcutaneous infusion of either saline or the centrally acting alpha-adrenoceptor agonist clonidine (10 micrograms/kg/h). In separate groups of similarly treated rats, the concentrations of neurotensin (NT), vasoactive intestinal polypeptide (VIP), cholecystokinin octapeptide (CCK-8), calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY) were measured in the cortex (COR), hypothalamus (HYP), medulla oblongata/pons (MO/P), and cervical (CSC) and thoracic (TSC) spinal cord. In comparison to the WKY rats, the SHR had significantly lower neuropeptide concentrations within the COR (NPY, CCK-8), HYP (NT), MO/P (NPY, NT, and CCK-8), CSC (all neuropeptides), and TSC (NPY, NT, CCK-8, and VIP). The infusion of clonidine lowered the MAP of the WKY and SHR rats (-10 and -35 mm Hg, as compared with respective saline controls) and HR in the WKY rats (-45 beats/min). In general, the infusion of clonidine produced decreases in neuropeptide levels within the CNS of the WKY rather than the SHR strain. When there was a strain difference (i.e., SHR less than WKY), it was evident, particularly within the spinal cord, that clonidine reduced the levels of the neuropeptides in the WKY rats to those levels in the SHR. These findings suggest that the reduced neuropeptide concentrations of the SHR (particularly those within the CSC) and TSC may be a result of, rather than a causal factor in, hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional brain concentrations of several putative peptide neurotransmitters in normotensive and spontaneously hypertensive rats: effects of continuous (10-day) clonidine infusion. 245 67

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

1. Spontaneously hypertensive rats (SHR) are useful for investigating the possible pathophysiological and neurochemical basis of human essential hypertension. 2. The accepted pathogenic mechanism of hypertension in SHR is an increased central sympathetic drive which results in an increased peripheral resistance. 3. The neurochemical basis of the increased sympathetic drive is unknown. The observation that there are reduced levels of neuropeptides (vasoactive intestinal peptide, neuropeptide Y, cholecystokinin octapeptide, neurotensin and calcitonin gene related peptide) in the spinal cord in SHR rats compared with age and gender matched Wistar-Kyoto normotensive rats could provide a basis for understanding the mechanism of hypertension in SHR.
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PMID:Altered levels of neuropeptides in the medulla and spinal cord of spontaneously hypertensive rats. 307 73

Changes in dopamine neurotransmission in the nucleus accumbens of the spontaneously hypertensive rat (SHR) may be involved in the pathogenesis of hypertension. This investigation tested the hypothesis that the sulfated octapeptide cholecystokinin (CCK8S) induced release of dopamine is greater in the SHR than in its normotensive control, the Wistar-Kyoto rat (WKY). Dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were sampled using microdialysis in the caudal half of the nucleus accumbens of 10-week-old anesthetized SHRs and WKYs. Samples were collected in the following order: 3 baseline, 3 CCK8S (10 mumol/l), and 3 postdrug samples. The samples were then analyzed using high pressure liquid chromatography with electrochemical detection. CCK8S increased dopamine and DOPAC levels in both the SHR and WKY with a larger increase in basal dopamine in the SHR (greater than 200%). Perfusion of the nucleus accumbens with 1 mumol/l of CCK8S or the nonsulfated form of CCK8 (CCK8US, 10 mumol/l) produced no significant increase in the release of dopamine in the SHR. These results indicate that CCK8S-induced release of dopamine in the nucleus accumbens is greater in the SHR. Changes in CCK8S neurotransmission/receptor function may be responsible for the alterations in dopaminergic function of the SHR and the pathogenesis of hypertension.
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PMID:Cholecystokinin-induced release of dopamine in the nucleus accumbens of the spontaneously hypertensive rat. 758 28

We employed receptor autoradiography to test the hypothesis that changes in cholecystokinin neurotransmission in the striatum of the young spontaneously hypertensive rat (SHR) is involved in the development of hypertension. The binding density of 125I-Bolton Hunter labelled cholecystokinin octapeptide (125I-BH-CCK8) in the striatum of 5-week-old prehypertensive SHRs and its normotensive control the Wistar-Kyoto rat (WKY) was determined using computer-assisted densitometry. We found a significant increase in 125I-BH-CCK8 binding density in the nucleus accumbens of the SHR. No difference between the binding density of 125I-BH-CCK8 was found in the caudate-putamen and the prefrontal cortex of SHRs and WKYs. These results suggest that changes in CCK8S neurotransmission or receptor function are not secondary to an increase in arterial blood pressure and, therefore, may be involved in the development of hypertension.
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PMID:Up-regulation of cholecystokinin receptors in the nucleus accumbens of the young prehypertensive spontaneously hypertensive rat. 764 45

The possibility that cholecystokinin in the striatum may be involved in hypertension was investigated using in vitro receptor autoradiography. The binding density of 125I-Bolton Hunter labeled cholecystokinin octapeptide (125I-BH-CCK8) was determined using computer-assisted densitometry in the striatum of the spontaneously hypertensive rat (SHR) and its control the Wistar-Kyoto rat (WKY). A significant increase in 125I-BH-CCK8 binding density was found in the lateral part of the caudate-putamen of the SHR. In contrast, a significant decrease in 125I-BH-CCK8 binding density was found in the posteromedial nucleus accumbens of the SHR. These results indicate that CCK8 receptor density is altered in the striatum of the SHR and suggest a role for CCK8 receptors in the pathophysiology of hypertension.
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PMID:Cholecystokinin receptor density in the striatum of the spontaneously hypertensive rat. 845 62

The effect of i.v. infusion of gastrin (CCK-4), cholecystokinin (CCK-8) and pancreatic polypeptide (PP), 20 and 200 ng/kg/min for 1 h, on gastrointestinal electrical activity and arterial pressure was studied in conscious miniature pigs. During infusion of CCK-8 a transient hypertension was observed. In the antrum, the 3 peptides provoked an increase in slow wave activity and a decrease in spike activity. In the intestine, CCK-8 induced an increase in ileal spiking activity, whereas infusion of PP resulted in an increased frequency of long spike bursts in the caecum.
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PMID:Effect of some gastrointestinal hormones on antral, small intestinal and caecal myoelectrical activity in the conscious miniature pig. 979 67

D(1)-like (D(1), D(5)) and D(2)-like (D(2), D(3), D(4)) dopamine receptors interact in the kidney to produce a natriuresis and a diuresis. Disruption of D(1) or D(3) receptors in mice results in hypertension that is caused, in part, by a decreased ability to excrete an acute saline load. We studied D(1)-like and D(2)-like receptor interaction in anesthetized spontaneously hypertensive rats (SHR) by the intrarenal infusion of Z-1046 (a novel dopamine receptor agonist with rank order potency of D(3)> or =D(4)>D(2)>D(5)>D(1)). Z-1046 increased glomerular filtration rate (GFR), urine flow, and sodium excretion in normotensive Wistar-Kyoto rats but not in SHRs. The lack of responsiveness to Z-1046 in SHRs was not an epiphenomenon, because intrarenal cholecystokinin infusion increased GFR, urine flow, and sodium excretion to a similar extent in the two rat strains. We conclude that renal D(1)-like and D(2)-like receptor interaction is impaired in SHRs. The impaired D(1)-like and D(2)-like receptor interaction in SHRs is not caused by alterations in the coding sequence of the D(3) receptor, the D(2)-like receptor expressed in rat renal tubules that has been shown to be involved in sodium transport. Because the diuretic and natriuretic effects of D(1)-like receptors are, in part, caused by an interaction with D(2)-like receptors, it is possible that the decreased Z-1046 action in SHRs is secondary to the renal D(1)-like receptor dysfunction in this rat strain.
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PMID:Impaired renal D(1)-like and D(2)-like dopamine receptor interaction in the spontaneously hypertensive rat. 1155 12

To explore the mechanism underlying cholecystokinin octapeptide (CCK-8) induced attenuation in pulmonary arterial hypertension (PAH) in endotoxic shock (ES), the effect of CCK-8 on the changes in rabbit pulmonary arterial reactivity induced by tumor necrosis factor-alpha (TNF-alpha) was observed with isolated arterial ring technique and by examination of nitric oxide synthase (NOS). The contractile response to 10(-6) mol/L phenylephrine (PE) and the endothelium dependent relaxation response to 10(-6) mol/L acetylcholine (ACh) were not affected by TNF-alpha (4000 U/ml) after incubation for 2 h; the relaxation response was decreased significantly when the incubation was prolonged to 7 or 14 h, which, however, could be reversed by a concomitant exposure to CCK-8 (0.5 microgram/ml), but the incubation of pulmonary arterial rings with CCK-8 (0.5 microgram/ml) alone did not bring out any contractile responses. The endothelium dependent relaxation response to 10(-6) mol/L ACh was restored by L arginine in the TNF-alpha group which had been incubated for 7 h, but was not affected by AG in each group, while the contractile response to 10(-6) mol/L PE increased significantly in the TNF-alpha group. The relaxant response to 10(-6) mol/L ACh changed into a contractile response after preincubation with L-NNA in each group, while the contraction response to 10(-6) mol/L PE increased significantly. The NOS activity increased in the TNF-alpha and the TNF alpha+CCK-8 groups, while no significant difference was observed between the vehicle and the CCK-8 groups. These results suggest that CCK-8 prevents TNF-alpha induced impairment in endothelium dependent relaxation response, and the effects of both CCK-8 and TNF-alpha are related to NO.
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PMID:[Role of nitric oxide in cholecystokinin octapeptide alleviation of tumor necrosis factor alpha induced changes in rabbit pulmonary arterial reactivity]. 1193 Feb 30


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