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

Wistar rats were selectively bred over 10 generations for differences in performance in a footshock-motivated brightness discrimination (BD) test in a Y-maze. High behavioral performance (Wis/HBP) and low behavioral performance (Wis/LBP) rat lines were obtained which differ significantly in all behavioral components tested: frequency of correct responses, number of trials to criterion, response latency (HBP less than LBP), and frequency of freezing behavior (HBP less than LBP), the latter suggesting differences in emotionality. In Wis/LBP rats, furthermore, the normal increase in behavioral performance between the training and the relearning session, which indicates the formation of a memory trace, disappeared during selection. In male breeders sampled during selection of the two lines (Wis/HBP: n = 17; Wis/LBP: n = 21), both arginine vasopressin (AVP) and oxytocin (OXT) contents were measured by radioimmunoassay in the motor cortex, septum/striatum, hippocampus, hypothalamus, medulla oblongata and posterior pituitary. Compared with the Wis/HBP rats, the Wis/LBP rats contained less AVP in the hippocampus (3.1 +/- 0.58 vs 8.3 +/- 1.4 pg/mg wet wt., mean +/- S.E.M., P less than 0.001), but more AVP in the medulla (1.7 +/- 0.20 vs 1.1 +/- 0.18 pg/mg, P less than 0.05). In contrast, no significant differences between the lines were detected with respect to OXT concentrations. In the Wis/LBP rats, moreover, the hippocampal AVP content decreased during selection (r = -0.645, P less than 0.01), while the acquisition response latency increased (r = 0.549, P less than 0.01). As a consequence, a significant, albeit weak, negative correlation (r = -0.483, P less than 0.05) was observed between the individual hippocampal AVP content and the response latency during acquisition. Thus, the results confirm the view that genetically determined differences in the hippocampal content of endogenous AVP may contribute to an individual's level of emotionality and behavioral performance.
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PMID:Vasopressin and oxytocin in brain areas of rats selectively bred for differences in behavioral performance. 161 70

The effect of endothelin (ET)-1 was investigated on resistance arteries of less than 300-microns lumen diameter from the mesenteric circulation, mounted on a wire myograph, in deoxycorticosterone acetate (DOCA)-salt hypertensive rats within 2 wk of developing hypertension and in uninephrectomized controls. Arteries from DOCA-salt hypertensive rats presented a significantly reduced external and lumen diameter and increased media width and wall cross-sectional area. Vessels from DOCA-salt hypertensive rats responded to ET-1 with lower active wall tension and media stress. Because the lumen diameter was significantly decreased in DOCA-salt hypertensive rats, the active pressure developed in response to ET-1 was similar in both groups. In contrast, the maximal tension response to arginine vasopressin was enhanced in DOCA-salt hypertensive rats. The sensitivity to both peptides and norepinephrine (NE) was similar in both groups. After removal of endothelium by exposure to the nonionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, ET-1 elicited tension responses that were also lower in DOCA-salt hypertensive rats, whereas NE responses were similar in both groups. These results demonstrate significant morphological and functional changes in small arteries of DOCA-salt hypertensive rats within 2 wk of developing hypertension and blunted reactivity to ET-1. Because similar results were found after removal of endothelium, it is likely that neither prior receptor occupation by endogenous ET nor acute effects of other endothelial cell products play a role in the reduced responsiveness to ET of vascular smooth muscle of small resistance arteries of DOCA-salt hypertensive rats.
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PMID:Effects of endothelin on resistance arteries of DOCA-salt hypertensive rats. 162 36

The aim of the present study was to examine the involvement of the sympathetic nervous system in the generation or release of vascular nitric oxide. In urethane-anesthetized rats, the administration of the novel nitric oxide synthesis inhibitor L-N-nitro arginine (LNA) (0.02 mmol/kg i.v.) increased mean arterial pressure and renal, mesenteric, and hindquarter vascular resistances. The intravenous administration of L-arginine (60 mg/kg plus 12 mg/kg/min i.v.) produced small reductions in arterial pressure and vascular resistances and abolished the hemodynamic effects of LNA. Pretreatment with the ganglion blocking agent chlorisondamine lowered mean arterial pressure and vascular resistances, abolished the LNA-induced pressor and renal vasoconstrictor response, and attenuated the increases in mesenteric and hindquarter resistances. In contrast, the vasodilator hydralazine lowered mean arterial pressure and vascular resistances to levels equivalent to that of ganglionic blockade; however, the subsequent administration of LNA still produced significant increases in arterial pressure and regional vascular resistances. In ganglion-blocked rats in which pressure and vascular resistances were returned to normal levels by infusion of arginine vasopressin or phenylephrine, the pressor and vasoconstrictor effects of LNA were restored. However, phenylephrine was significantly more efficacious and markedly exaggerated the action of LNA. These results suggest that the sympathetic nervous system plays an important role in modulating the synthesis or release of vascular nitric oxide through the effects of 1) normal sympathetic discharge, 2) humoral activation of alpha-adrenergic receptors, and 3) vascular tone per se.
Hypertension 1991 Jun
PMID:Role of sympathetic nerve activity in the generation of vascular nitric oxide in urethane-anesthetized rats. 167 5

Endothelial cells can produce contracting factors; endothelin, a 21-amino acid peptide that can control local vascular tone, is the most potent of these factors. Of the three isoforms of endothelin, endothelial cells appear to release primarily endothelin-1. The peptide is formed from its precursor big endothelin via the activity of the endothelin converting enzyme. The basal production of the peptide is stimulated by epinephrine, angiotensin II, arginine vasopressin, transforming growth factor beta, thrombin, interleukin-1, and the calcium ionophore A23187. In vascular smooth muscle cells, endothelin binds to a specific receptor that activates phospholipase C and leads to the formation of inositol trisphosphate, diacylglycerol, and increased intracellular calcium levels. In certain blood vessels, the endothelin receptor is linked to a voltage-operated calcium channel via a Gi protein. This may explain why calcium antagonists inhibit endothelin-induced contractions only in certain blood vessels. In the human forearm circulation, calcium antagonists of different classes prevent endothelin-induced contractions. In hypertension, the circulating endothelin levels appear to be normal, whereas the vascular sensitivity to the peptide is reduced in most vascular tissues, but normal and enhanced responses have also been reported. In atherosclerosis and other forms of vascular disease, circulating endothelin levels are augmented, a phenomenon that may be related to an increased formation of the peptide induced by modified forms of low-density lipoproteins.
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PMID:Endothelin. 172 99

One of the mechanisms of glucocorticoid-induced hypertension has been thought to be the enhancement of vascular responsiveness to vasoconstrictors. In this regard, the effects of glucocorticoids on inositol trisphosphate production in vascular smooth muscle cells were studied. Angiotensin II and arginine vasopressin transiently increased inositol trisphosphate formation in a dose-dependent manner. Pretreatment with dexamethasone for 48 hours shifted the dose-response trisphosphate curves of angiotensin II- and arginine vasopressin-induced inositol trisphosphate production to the left, that is, it significantly reduced the half-maximal effective concentrations of angiotensin II (from 25 nM to 5 nM) and arginine vasopressin (from 50 nM to 25 nM). These effects of dexamethasone required a minimum of 12 hours of incubation; maximum effect was observed after 24 hours of treatment. A glucocorticoid antagonist, RU 38486, completely blocked these effects. To elucidate the interaction with prostaglandin, we used indomethacin, a potent inhibitor of prostaglandin synthesis. Treatment with indomethacin shifted the dose-response curves of angiotensin II- and arginine vasopressin-induced inositol trisphosphate production to the left. However, this shift was less than that seen after dexamethasone treatment. Indomethacin alone did not completely reproduce dexamethasone effects, and no additive effect between indomethacin and dexamethasone was observed. These results suggest, at least in part but not entirely, that the effects of dexamethasone depended on prostaglandin synthesis inhibition. We concluded that glucocorticoids altered the responsiveness of vascular smooth muscle cells to angiotensin II and arginine vasopressin through a glucocorticoid-specific receptor. These actions strongly support the mechanism by which the glucocorticoid induced hypertension through the increased sensitivity to vasoconstrictors.
Hypertension 1992 Jan
PMID:Potentiation of inositol trisphosphate production by dexamethasone. 173 Apr 35

Details of the interdependent, trophic relation between smooth muscle and its neural innervation are not well known despite suggestions that neural influences may contribute significantly to hypertensive and other cardiovascular disease. Vascular smooth muscle is a major target of innervation by neurons of the sympathetic nervous system. Sympathetic neurons depend on a constant supply of the potent neurotrophic peptide nerve growth factor. Nerve growth factor regulates an impressive list of neuronal and perhaps muscle properties, yet its source in vessels and the determinants of its synthesis are not known. We have taken advantage of the cytoarchitecture of the aorta to demonstrate that vascular smooth muscle cells synthesize nerve growth factor. The survival of cultured sympathetic neurons is supported in a nerve growth factor-dependent manner by co-culture with pure rat aortic vascular smooth muscle cells. Furthermore, pure smooth muscle cell cultures contain nerve growth factor-specific messenger RNA. Levels of messenger nucleic acid coding for nerve growth factor in smooth muscle are regulated by contractile agonists (angiotensin II, arginine vasopressin) and the adrenergic agonist phenylephrine. This suggests a link between muscle activity and growth factor production. Secretion of nerve growth factor protein by vascular smooth muscle was measured using a sensitive two-site immunoassay. Secretion is highest during muscle growth. Secretion is elevated by angiotensin II and arginine vasopressin but slightly inhibited by phenylephrine. These results suggest that cultured vascular smooth muscle can serve as a useful model in which to study the cellular regulation of trophic factor synthesis in health and disease.
Hypertension 1991 Dec
PMID:Nerve growth factor synthesis in vascular smooth muscle. 174 54

An orally effective, nonpeptide, vasopressin V1 receptor antagonist, OPC-21268, has been identified. This compound selectively antagonized binding to the V1 subtype of the vasopressin receptor in a competitive manner. In vivo, the compound acted as a specific antagonist of arginine vasopressin (AVP)-induced vasoconstriction. After oral administration in conscious rats, the compound also antagonized pressor responses to AVP. OPC-21268 can be used to study the physiological role of AVP and may be therapeutically useful in the treatment of hypertension and congestive heart failure.
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PMID:OPC-21268, an orally effective, nonpeptide vasopressin V1 receptor antagonist. 185 May 53

Release of endothelin-1, a novel potent vasoconstrictor peptide originally isolated from endothelial cells, from cultured bovine endothelial cells has been shown to be stimulated by arginine vasopressin and angiotensin II. To elucidate the cellular mechanism by which endothelin-1 is released by these vasoconstrictors, we tested the effects of several compounds on the agonist-induced endothelin-1 release and studied the changes of cytosolic free Ca2+ concentrations and phosphoinositide breakdown by these agonists in cultured bovine endothelial cells. Protein kinase C inhibitors (H-7, staurosporine), an intracellular Ca2+ chelator, and an inhibitor of phospholipase C (neomycin), all abolished the agonist-induced endothelin-1 release, whereas the Ca2+ channel blocker nicardipine was ineffective. Although synthetic 1,2-diglyceride (diolein) dose dependently stimulated endothelin-1 release, downregulation of protein kinase C after pretreatment with phorbol ester resulted in decreased effects to increase endothelin-1 release by the agonists. Both arginine vasopressin and angiotensin II induced immediate and transient increases in intracellular Ca2+ levels of fura-2-loaded endothelial cells as well as formation of inositol trisphosphate; the agonist-induced intracellular Ca2+ increases were not affected either by nicardipine or by chelating extracellular Ca2+. The arginine vasopressin- and angiotensin II-induced intracellular Ca2+ increases, inositol trisphosphate formation, and endothelin-1 release were completely abolished by V1-receptor antagonist and saralasin, respectively. It is concluded that arginine vasopressin and angiotensin II stimulate the release of endothelin-1 by a common mechanism, involving receptor-mediated mobilization of intracellular Ca2+ and activation of protein kinase C in endothelial cells.
Hypertension 1991 Aug
PMID:Cellular mechanism of endothelin-1 release by angiotensin and vasopressin. 190 4

We investigated the structure and reactivity of small resistance arteries of two-kidney, one-clip (2K,1C) and one-kidney, one-clip (1K,1C) Goldblatt hypertensive rats within 4-6 wk of development of hypertension. Blood vessels from the mesenteric vascular bed with lumen diameter less than 300 microns were mounted on a wire myograph. The media of the vessel wall was significantly increased and lumen diameter was decreased in 2K,1C and 1K,1C rats. External diameter of blood vessels was reduced in both 2K,1C and 1K,1C rats, whereas cross-sectional area of the wall was increased significantly in 1K,1C rats. Wall tension in response to KCl was significantly lower in 2K,1C and 1K,1C hypertensive rats, whereas tension in response to norepinephrine (NE) was reduced in 1K,1C hypertensive rats but was similar in 2K,1C rats and controls. Active tension in response to arginine vasopressin (AVP) was similar in all groups. As a consequence of the reduced lumen circumference of small arteries, effective pressure in response to NE was similar in hypertensive and control rats, whereas effective pressure in response to AVP was exaggerated in the hypertensive rats. The sensitivity to NE and AVP was similar in all groups. These results show the rapid development of functional and structural changes in small resistance arteries in renal hypertensive rats within 4-6 wk of hypertension, with significant reduction in external and lumen diameters, increased media width, and increased media-to-lumen ratio, which enhance vascular reactivity to vasoconstrictors, in particular NE and AVP.
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PMID:Morphological and functional alterations of mesenteric small resistance arteries in early renal hypertension in rats. 192 99

The serial changes in systemic and renal hemodynamics, water and electrolyte balances and various vasoactive hormones were examined in 12 conscious dogs before, during (10 days) the administration of dexamethasone (DEX: 0.5 mg/kg/day) and after the cessation of DEX. In addition, during the administration of DEX, pressor responses to angiotensin II, norepinephrine, an angiotensin II analogue, saralasin, and an alpha-1-blocker, prazosin, were studied. Abrupt elevation of blood pressure to 106 +/- 5 mmHg on Day 1 (vs. 91 +/- 6 mmHg control: P less than 0.05) associated with marked increases in total peripheral resistance (P less than 0.01) was shown in DEX treated animals. Accompanied with these changes, renal blood flow increased to 146 +/- 12 ml/min (vs. 103 +/- 8 ml/min control: P less than 0.05) on Day 1 and maintained. In contrast, the results of serial alterations in hormones could not show any significant changes except significant elevations in atrial natriuretic peptide and reductions of cortisol and arginine vasopressin. Also, marked natriuresis and diuresis were observed in DEX administration dogs. Pressor response to norepinephrine was significantly increased and administration of either saralasin and prazosin significantly reduced the blood pressure of DEX treated animals. These results in DEX-treated conscious dogs confirmed our previous findings in human and rats. Glucocorticoid-induced hypertension mainly depends on the increases in total peripheral resistance but not volume factors.
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PMID:Characterization of alterations of hemodynamics and neuroendocrine hormones in dexamethasone induced hypertension in dogs. 193 41


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