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

Previous studies have focused on the role of the central nucleus of the amygdala (CeA) in cardiovascular and other amygdaloid functions. The combined retrograde tracing/immunohistochemical method was used to test for the presence of enkephalin, neurotensin, neuropeptide Y, and catecholamine neurons within the nucleus of the solitary tract that send efferents to the CeA. After injections of retrograde tracer into the CeA, retrogradely labeled neurons were observed within the caudal, medial nucleus of the solitary tract. Most CeA-projecting neurons were located ipsilaterally within the medial nucleus of the solitary tract at the level of the area postrema. Retrogradely labeled enkephalin- and neurotensin-immunoreactive neurons were found within the medial nucleus of the solitary tract at this level, while retrogradely labeled neuropeptide Y-immunoreactive neurons were found within the medial nucleus of the solitary tract rostral to the area postrema. About 60-74% of CeA-projecting cells were also immunoreactive for tyrosine hydroxylase. Approximately 9% of retrogradely neurons were phenylethanolamine-N-methyltransferase immunoreactive. The results provide evidence that within the nucleus of the solitary tract, peptidergic CeA-projecting neurons have a topographic distribution. In addition, noradrenergic neurons within the A2 group, rather than adrenergic neurons of the C2 group, provide the bulk of catecholaminergic input to the CeA from the nucleus of the solitary tract. Cell counts indicate that each of these peptides may be colocalized (to varying extents) within catecholamine-producing neurons. Also the catecholaminergic and enkephalinergic contribution to the ascending pathway from the nucleus of the solitary tract to the CeA distinguishes it neurochemically from the descending pathway. Thus, although there are afferent and efferent connections between the nucleus of the solitary tract and CeA, their peptidergic/neurotransmitter connections are not necessarily reciprocal. Input from nucleus of the solitary tract peptidergic and catecholaminergic neurons to the CeA may be important in the etiology of a number of pathophysiological conditions including hypertension, gastric ulcers, and schizophrenia.
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PMID:Organization of peptidergic and catecholaminergic efferents from the nucleus of the solitary tract to the rat amygdala. 198 Nov 74

DuP 532 is a novel nonpeptide angiotensin II (AII) receptor antagonist under development for the treatment of hypertension. DuP 532 is a more potent antihypertensive agent in renal hypertensive rats (ED30 = 0.042 mg/kg, i.v.) and displays a similar or longer duration of action than the previously described AII antagonist, DuP 753. DuP 532, in contrast to DuP 753, is a noncompetitive antagonist of AII-induced contractions of rabbit aortic strips (KB = 1.1 x 10(-10) M). However, the inhibition of AII binding by DuP 532 in rat adrenal cortex does not correlate with either the aortic contractile response or with the hypotensive response. Assay conditions were evaluated and the presence or absence of BSA was shown to markedly affect the apparent binding affinity of DuP 532 and other 5-carboxylic acid derivatives. DuP 753 and other compounds were much less affected. The IC50 for DuP 532 was 4.7 x 10(-6) M with and 3 x 10(-9) M without BSA. The IC50s for DuP 753 were 1.7 x 10(-8) M with and 5 x -9 M without BSA. Both compounds with or without BSA did not completely inhibit AII binding which is characteristic of AT1 selectivity. BSA also reduced the effect of DuP 532 on the AII-induced contractions of rat main pulmonary artery preparations and the AII-induced Ca2+ mobilization in rat aortic smooth muscle cells. DuP 532 was very specific for AT1 receptors and did not interfere with receptors associated with neurotensin, prazosin, bradykinin, nitrendipine, or vasopressin. It is concluded that DuP 532 represents a new class of specific, but noncompetitive. AII receptor antagonists whose binding characteristics may provide new insight into AII receptor function.
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PMID:DuP 532: a second generation of nonpeptide angiotensin II receptor antagonists. 204 7

The role of the brain kallikrein-kinin system in the regulation of arterial blood pressure of normotensive and spontaneously hypertensive rats was evaluated. Intracerebroventricular administration of the kinin antagonist [DArg0]Hyp3-Thi5,8[DPhe7]bradykinin caused no change in mean blood pressure in Wistar-Kyoto, Sprague-Dawley, or spontaneously hypertensive rats. The antagonist proved to be very potent in blocking the pressor effect of intracerebroventricular bradykinin (32 +/- 3 vs. 3 +/- 1 mm Hg, p less than 0.01). It was specific, as the pressor effect induced by other unrelated peptides was similar during the infusion of either vehicle or kinin antagonist (angiotensin II, 25 +/- 4 vs. 26 +/- 2 mm Hg; prostaglandin E2, 48 +/- 3 vs. 47 +/- 8 mm Hg; norepinephrine, 17 +/- 2 vs. 18 +/- 2 mm Hg; leucine-enkephaline, 15 +/- 2 vs. 16 +/- 1 mm Hg; neurotensin, 18 +/- 2 vs. 19 +/- 1 mm Hg; substance P, 19 +/- 2 vs. 19 +/- 2 mm Hg). Intracerebroventricular administration of 1 mg captopril, an inhibitor of kininase II (one of the enzymes responsible for kinin degradation), caused no change in mean blood pressure in normotensive rats, whereas it increased mean blood pressure by 44 +/- 9 mm Hg (p less than 0.01) in spontaneously hypertensive rats. This increase in mean blood pressure was blocked and then reversed into a hypotensive effect (22 +/- 6 mm Hg, p less than 0.05) during the infusion of kinin antagonist. Our data suggest that the pressor effect induced by intracerebroventricular captopril is due to a transient elevation in endogenous brain kinin levels, supporting the hypothesis that the brain kallikrein-kinin system plays a role in the central regulation of blood pressure in spontaneously hypertensive rats.
Hypertension 1990 Apr
PMID:Brain kinins are responsible for the pressor effect of intracerebroventricular captopril in spontaneously hypertensive rats. 218 Aug 19

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

The purpose of the present study was to investigate the effects of vasoactive neuropeptides, such as substance P or neurotensin, on vascular adrenergic neurotransmission in hypertension. In perfused mesenteric vasculatures prepared from spontaneously hypertensive rats (SHR), we examined the effects of substance P and neurotensin on vascular responsiveness and noradrenaline release from the sympathetic nerve endings. Stimulation-evoked noradrenaline release and pressor responses were inhibited by substance P and neurotensin. In SHR, the noradrenaline release and pressor responses during electrical nerve stimulation were significantly greater than in Wistar-Kyoto rats (WKY). The inhibitory effects of these responses by substance P and neurotensin were attenuated in SHR compared with WKY. These results showed that substance P and neurotensin could affect the presynaptic site of the blood vessels and cause a decrease in electrically stimulated noradrenaline release from the vascular adrenergic neurons. The reduction of noradrenaline release and pressor responses by substance P and neurotensin in SHR might suggest insufficient regulation of the vascular adrenergic transmission by these vasoactive peptides in hypertension.
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PMID:Role of substance P and neurotensin in the regulation of neurosecretion and vascular responsiveness in hypertension. 246 74

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

The present study attempts to compile information on the possible physiologic role of the endogenous peptide neurotensin (NT) as a hormone and/or neurotransmitter. The methodological approach is immunohistochemical localization of NT in the entero-endocrine system as well as in the central and peripheral nervous systems. The results found in the three systems are first related to the pharmalogical and physiological findings in the literature. Subsequently their significance is discussed for each organ separately before attempting a final overall interpretation. Briefly, the present study reveals the following essential findings: The occurrence and distribution of NT-IR entero-endocrine cells (N-cells) in different mammals including man, as well as in representative members of all classes of vertebrates and higher invertebrates, are analyzed and evaluated morphometrically. The NT-IR cells in all investigated species are demonstrated to be of the open type. The innervation of paravertebral and prevertebral ganglia by NT-IR fibers is described; at least a portion of these fibers is thought to originate in NT-IR perikarya of the substantia intermedia of the spinal cord. The involvement of these NT-IR fibers in the regulation of systemic blood flow (hypertension) is suggested. The existence of NT-IR innervation of the gastro-intestinal tract is considered to be a general phenomenon. This notion is reaffirmed by phylogenetic investigation of the NT-IR enteric nerves. The pharmacological effects of NT in different portions of the gastro-intestinal tract, reported in the literature are related to the immunohistochemical localization of NT. In light of the present results, some of the effects of NT which were previously considered to be of an endocrine or paracrine nature - such as contraction of the guinea-pig ileum - are interpreted as effects of NT of neuronal origin. The specific NT-IR innervation of target cells in the exocrine pancreas (vascular smooth muscle, acinar cells) is demonstrated, and participation of NT-IR nerve fibers in regulation of the secretion of pancreatic juice is postulated. The innervation of the heart (coronary vasculature, myocardium, conduction system) by NT-IR fibers is demonstrated in various mammals and for the first time also in man. The cardiac NT-IR nerve fibers are thought to be the cytological substrate for different NT effects on heart action (coronary vasoconstriction, positive inotropy and chronotropy) reported in the literature.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurotensin. Immunohistochemical localization in central and peripheral nervous system and in endocrine cells and its functional role as neurotransmitter and endocrine hormone. 285 33

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

The occurrence of neuropeptide Y (NPY)-like immunoreactivity (LI) in the adrenal gland of several species as well as in tumor tissue and plasma from pheochromocytoma patients was investigated. NPY-LI was present in chromaffin cells of the adrenaline type in all species investigated except in the pig, as demonstrated by a colocalization of NPY-LI and the adrenaline-synthetizing enzyme phenylethanolamine N-methyltransferase (PNMT). NPY-LI in the adrenaline cells of the cat was clearly separated from the neurotensin-LI in the noradrenaline dopamine-beta-hydroxylase-positive, PNMT-negative cells. NPY-LI seems to co-exist with enkephalin-like material in the chromaffin cells. In addition, NPY-LI was present in nerves both within the adrenal cortex and medulla. The highest levels of NPY-LI were found in mouse and cat, while only a very low amount of NPY-LI was present in the pig adrenal. Characterization of the adrenal NPY-LI by reversed-phase high-performance liquid chromatography revealed that the main peak was similar to porcine NPY. In addition, two minor peaks of NPY-LI were present. High levels of NPY-LI were found in plasma and tumors from the pheochromocytoma patients. During manipulation of the tumors upon surgical removal, there was a marked increase in plasma NPY-LI in parallel with the raise in catecholamines and in blood pressure. At least two forms of NPY-LI were present in plasma and tumor extracts from pheochromocytoma patients with the main peak corresponding to porcine NPY. Since NPY exerts vasoconstrictor effects, it may be postulated that NPY contributes to the adrenal cardiovascular response and to the hypertension seen in pheochromocytoma patients.
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PMID:Neuropeptide Y-like immunoreactivity in adrenaline cells of adrenal medulla and in tumors and plasma of pheochromocytoma patients. 351 67

Polypeptides are endogenous agents, involved in the regulation of many physiologic functions and the pathogenesis of several diseases. Polypeptide antagonists form a group of new chemical entities which may provide valid therapeutic agents. Some polypeptides (angiotensin, kinins) are released through the action of proteolytic enzymes (renin, kallikreins) and act as hormones or autacoids; others (substance P, neurotensin) are synthetized by nervous cells to serve as neurotransmitters or neuromodulators. The main homeostatic role of the renin-angiotensin system is to uphold high systemic arterial blood pressure. Overproduction of renin and insufficient checking of renin secretion are among the most common causes of arterial hypertension. Several forms of arterial hypertension (neurovascular, idiopathic) benefit from a reduction in renin-angiotensin system activity. This is achieved either through decreasing renin secretion, by inhibiting conversion of angiotensin I into angiotensin II, or through blocking the peripheral actions (at the receptor sites) of angiotensin II. Renin secretion is very significantly reduced by beta-blocking agents (propranolol); conversion of angiotensin I into angiotensin II is inhibited by teprotide, captopril and their derivatives; peripheral actions of angiotensin II are blocked by saralasin. Bradykinin and related agents produce vasodilation, increase vascular permeability and stimulate pain fibers. Kinins thus reproduce the cardinal features of inflammation and are held to be mediators of the inflammatory reaction. The substance P neuropeptide is found in the brain and bowel; it may act as a transmitter of the sensation of pain at the spinal cord and central nervous system sites. Among other effects outside of the brain, substance P is a potent vasodilator and inhibits renin secretion. Neurotensin is a neuropeptide which produces hypothermia, muscular relaxation and analgesia. Outside of the brain, this peptide is involved in the regulation of gastric secretion, intestinal motility and insulin and glucagon secretion. The vasoactive intestinal peptide, found in certain cholinergic nerve endings, is a large peptide which inhibits gastric secretion, intestinal motility and vascular tone.
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PMID:[Polypeptides and antagonists]. 620 6


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