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

Our study examines the long-term cardiovascular effects after a brief period of angiotensin converting enzyme (ACE) inhibitor treatment in young spontaneously hypertensive rats (SHR). SHR were treated with perindopril (3 mg/kg/day) by gavage from 2 to 6, from 6 to 10, or from 2 to 10 weeks of age. Systolic blood pressure was measured in the tail weekly until 25 weeks of age. Corresponding control groups received distilled water for the same periods. In each treatment group blood pressure was reduced significantly during treatment, rose when treatment stopped, but plateaued significantly below control SHR thereafter. This difference in blood pressure at 25 weeks of age was due to reduced total peripheral resistance as determined by microsphere methods, but plasma renin activity and angiotensin II concentrations were not different. Cardiac hypertrophy was also reduced in treated SHR. In a separate experiment, perindopril treatment from 6 to 10 weeks of age resulted in a significant reduction in the media/lumen ratios of mesenteric resistance vessels at 32 weeks of age. Concomitant administration of angiotensin II with perindopril from 6 to 10 weeks of age not only prevented the long-term effects on blood pressure seen with perindopril treatment alone but was associated with cardiovascular hypertrophy in excess of untreated control SHR. Finally, perindopril given for a shorter period (6 to 7 weeks) or later in life (20 to 24 weeks) had no significant long-term effects on blood pressure. These results demonstrate that a 4-week period of ACE inhibitor treatment in young SHR is sufficient to prevent the full expression of genetic hypertension and cardiovascular hypertrophy and that angiotensin II might be important in the development of hypertension in this model, its role in later life being less important.
Hypertension 1990 Dec
PMID:Brief angiotensin converting enzyme inhibitor treatment in young spontaneously hypertensive rats reduces blood pressure long-term. 224 28

Erythrocyte Na-K cotransport is high and genetically correlated to hypertension in Milan hypertensive strain (MHS) rats. In man there is a substantial overlap of individual values between essential hypertensives and controls. However, the findings in rat strains with different types of genetic hypertension suggest that Na-K cotransport studies may throw light on the different pathogenetic mechanisms of the human disease. In 28 normotensive and 22 hypertensive families the midparent-offspring correlation of Na-K cotransport values was significant only in hypertensive families (r = 0.48) and not significant in normotensive ones (r = 0.06), indicating genetic polymorphism for its phenotypic expression only in the hypertensives. In 189 essential hypertensives and 109 normotensives carefully selected from a population-based screening in order to exclude uneven sampling bias, analysis for the bimodality of the distribution of Na-K cotransport clearly showed that normotensives are distributed unimodally and hypertensives bimodally, with nadir of the distributions at about 450 mumols (1 RBC/h). Dividing the hypertensives according to Na-K cotransport value, the high Na-K cotransport subgroup has lower fractional percent excretion of uric acid and plasma renin activity. These data suggest that the high Na-K cotransport subgroup has peculiar characteristics of greater proximal tubular reabsorption (lower fractional excretion of uric acid) that may cause body volume expansion (lower plasma renin activity).
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PMID:Genetic polymorphism of Na-K cotransport in essential hypertension. 225 61

To investigate the brain stem monoamine mechanism in the development and maintenance of hypertension of spontaneously hypertensive rats (SHR), we determined monoamine contents and norepinephrine turnover in discrete brain stem nuclei which are known to relate with cardiovascular control. Specific areas and brain stem nuclei were dissected from serial frozen slices of 300 microns thickness according to the atlas of Palkovits and Jacobowitz. The dissected tissues were homogenized, centrifuged and the supernatants were injected into high performance liquid chromatography with electrochemical detection (HPLC-ECD). Norepinephrine (NE), dopamine (DA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) contents were determined. NE turnover was also determined 2 hour after alpha-methyl-p-tyrosine administration (250 mg/kg, i.p.). In 4-week old SHR, the only significant change observed was decreased NE contents in the nucleus tractus solitarii (NTS). Such decreases in NE contents of the NTS were also found in 8- and 16-week old SHR. However, there were no differences in NE turnover in the NTS between SHR and WKY. Increased NE contents were found in the A1, A5, and nucleus reticularis gigantocellularis (RG) in the later stages (8 and 16 weeks) in SHR. Furthermore, increased NE turnover was seen in the RG of SHR at 16-week old, indicating increased neuronal activity. Dopamine, 5-HT and 5-HIAA showed no consistent changes between SHR and WKY. Increased NE levels were observed in later stages after development of hypertension, suggesting the increased NE in adult SHR may represent a central adaptive change secondary to the established hypertension. Since increased NE levels were consistently found in or around the regions which are known as vasomotor centers, we assume that these increased NE might serve to maintain hypertension or to inhibit a further increase in blood pressure. In contrast, the NE contents were decreased with constant turnover in NTS of SHR aged 4, 8, and 16 weeks. Constant turnover in NE could not compensate for reduced NE in NTS and may lead to a functional reduction or reduced noradrenergic activity. This defect in intrinsic noradrenergic neurons in NTS may trigger the development of genetic hypertension in SHR. In conclusion, the present results demonstrate that NE levels of SHR in the NTS were consistently decreased compared with those of WKY in all age groups. In later stages, increased NE levels were observed in A1, A5 and RG of SHR. These results indicate that brain stem monoamine system, especially noradrenergic neurons, contributes to the development and maintenance of hypertension in SHR.
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PMID:[Monoamine contents and norepinephrine turnover in brain stem nuclei of young and adult spontaneously hypertensive and Wistar-Kyoto rats]. 227 99

To gain further insight into the possible generalized nature of intracellular calcium-related alterations in hypertension we measured free cytosolic calcium (iCa2+) in lymphocytes obtained from the spleen and the blood of the spontaneously hypertensive rat (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats. By monitoring Fura-2 fluorescence at an excitation wavelength of 340 nm and an emission wavelength of 510 nm we estimated; Ca2+. In peripheral lymphocytes from the SHR iCa2+ was increased as compared to those from WKY rats (146 +/- 14 and 112 +/- 6.0 nm, respectively, P less than .025). In contrast, in lymphocytes obtained from the spleen, iCa2+ was not different between SHR and WKY rats (93 +/- 7.0 and 96 +/- 8.0 nm, respectively). When spleen cells were subjected to selective B lymphocyte depletion to generate a preparation of predominantly T lymphocytes, iCa2+ was found to be higher in SHR than in WKY rats (149 +/- 23 and 89 +/- 12 nm, respectively, P less than .05). The finding that iCa2+ is elevated in peripheral lymphocytes and spleen cells subjected to B cell depletion but not in untreated spleen cells indicates that T, but not B, lymphocytes have increased iCa2+ in the SHR. This observation may be related to existing evidence that T lymphocyte function is impaired in the SHR. An increase in iCa2+ is not a phenomenon generalized to all cells of this model of genetic hypertension.
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PMID:Cytosolic calcium in T lymphocytes from the spontaneously hypertensive rat. 235 Apr 73

gamma-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter and has been shown to exert considerable influence on the neural control of the cardiovascular function. It is not clear, however, which GABAergic systems are involved in salt-induced hypertension. This study was designed to investigate the GABAergic neurons in specific regions of the brain possibly linked to salt-induced hypertension. After 4 weeks of deoxycorticosterone acetate (DOCA) and salt treatments, the rats developed cardiac hypertrophy. All of the animals were sacrificed for immunocytochemical localization of GABAergic terminals using specific antibodies to glutamic acid decarboxylase (GAD). GAD-positive GABAergic terminal densities in discrete regions of the brain were determined by using morphometric quantitation. Results showed that GABAergic terminal densities in the medial preoptic nucleus and the area lateral to the paraventricular hypothalamic nucleus were significantly increased in DOCA-salt-treated rats 4 weeks after the experiment as compared with 4 week controls. This study provides new evidence to support further the idea that central GABAergic neurons are closely associated with pathogenesis of salt-induced hypertension. Different hypertensive mechanisms between salt-induced hypertension and genetic hypertension are also discussed.
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PMID:Increased density of glutamic acid decarboxylase-containing terminals in the medial preoptic nucleus and the area surrounding the paraventricular hypothalamic nucleus is associated with deoxycorticosterone acetate (DOCA)-salt hypertension. 239 3

Alterations in the relationship between the degree of left ventricular hypertrophy and the maximum pressure generating capacity were assessed in two models of genetic hypertension in rats. Both the spontaneously hypertensive rat (SHR) and the Dahl salt-sensitive (DS) rat developed systemic hypertension and progressive increases in left ventricular mass. In the DS rat, the magnitude of the hypertension and ventricular hypertrophy produced was in direct relation to the level of dietary sodium intake. At 6 months of age, the pressure generating capacity of all hypertensive rats was directly related to the left ventricular weight/body weight ratio. With the moderate level of hypertrophy observed in the 12-month-old SHRs and DS rats on a low salt diet, the correlation between left ventricular weight and augmented pressure generating capacity during isovolumic contractions was maintained. With the more severe degrees of left ventricular hypertrophy observed in 18- and 24-month-old SHRs and 12-month-old DS rats on a moderate salt diet, the further addition of ventricular mass was no longer associated with a proportional augmentation in maximal pressure development. These studies suggest that in genetic hypertension in rats, both the magnitude and duration of the hypertension are important determinants of the degree of hypertrophy and the functional status of the ventricle.
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PMID:Left ventricular hypertrophy and pressure generating capacity in aging genetically hypertensive rats. 240 68

In this article, we review the data about Na+ and K+ lymphocyte content in young subjects with borderline hypertension. These data indicate that many borderline subjects have an abnormally high lymphocyte Na+ content (Nai) and that their pressor response to stress and exercise is directly related to Nai. Lymphocyte K+ content (Ki) is increased in about 50% of borderline subjects. Subjects in whom Ki is high, in comparison with those having a normal Ki, have a lower Nai and lower diastolic blood pressure. This suggests that these subjects have an activation of some compensatory mechanism, possibly an increase in sodium pump function. A humoral factor causing an increase in Nai was detected not only in the plasma from essential hypertensives, but also in the plasma from borderline subjects and from normal subjects with familial hypertension having high Nai. This indirect evidence of a plasma factor impairing Na+ transport was confirmed by direct measurements of the plasma ability to inhibit Na+/K+ adenosine triphosphate. Moderate short-term dietary salt restriction reduces Nai and, proportionally, pressor response to stress. In the long-term, resting blood pressure is also reduced. Dietary K+ supplementation reduces pressor response to handgrip but not resting blood pressure. Intralymphocytic Na+ content is a good predictor of future sustained hypertension, since subjects with normal Nai do not develop hypertension within 5 years, whereas subjects with high Nai develop hypertension in 31% of cases. These subjects also have an altered pressor response to mental stress and do not respond to the low-salt diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cellular and humoral factors in borderline hypertension. 242 78

Adult cardiac myocytes are incapable of mitosis. Dead cells are replaced by connective tissue so that after myocardial infarction (MI), function can only be restored by compensatory hypertrophy of the surviving myocardium. In physiological hypertrophy in response to exercise, high altitude, or mild hypertension, additional myoplasm expands cell diameter in an orderly fashion; Z-lines are in register and the normal ratio of volume densities of contractile elements, mitochondria, and capillaries is conserved. In hypertrophy induced by aortic or pulmonary artery banding or by experimental or congenital hypertension, the borderline between physiological and pathological hypertrophy may be crossed, causing disorganization of fibers and an unfavourable contractile element to capillary ratio. There was, therefore, a need for a graded model of hypertrophy, which involves simulating an altitude of 6,000 m at sea level by supplying rabbits with appropriate nitrogen/oxygen mixtures. In this environment, 50% right ventricular hypertrophy can be achieved without alteration of left ventricular weight or hematocrit. Longer exposures produced 100% right ventricular hypertrophy, with only moderate increases in hematocrit and left ventricular weight. It is well known that adrenergic stimulation causes cardiac hypertrophy, and it has been suggested that release of a trophic factor from sympathetic nerves, either noradrenaline or a protein, might be a necessary stimulus for growth. If so, long-term treatment of post-MI patients with beta-adrenergic blocking agents could inhibit a desirable compensatory hypertrophy of the surviving myocardium. In the above model it has been found, however, that neither beta-blockade nor chemical sympathectomy with guanethidine or 6-hydroxydopamine had any effect on the hypertrophy, nor did treatment with verapamil or nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ventricular hypertrophy--physiological mechanisms. 242 5

Recent studies in essential hypertensive patients and rats with genetic hypertension strongly suggested that the development of primary hypertension takes place by a transient and chronic "cascade" of events (i) excess Na+ intake, (ii) secretion of natriuretic factors, (iii) abnormal cells Na+ homeostasis in the vascular wall, due to the presence of inherited abnormalities in different Na+ transport systems, and (iv) increase in cytosolic free Ca2+ content and catecholamines. Canrenone, an antihypertensive drug, behaves like a partial agonist at the digitalis-receptor site of the Na+, K+ pump. We observed here that (i) a 4 hr preincubation of human red cells with this compound increases its antagonistic properties against ouabain, (ii) in cultured smooth muscle cells, canrenone counterbalances the increase in cytosolic free Ca2+ induced by ouabain, and (iii) in a model of experimental hypertension with increased endogenous "ouabain-like" factors (rats with reduced renal mass), the administration of canrenone tends to normalize Na+, K+-pump activity and decrease blood pressure.
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PMID:Involvement of natriuretic hormones and Na+ transport in the antihypertensive action of canrenone. 242 26

Passive and active carrier-mediated transport of sodium across vascular muscle membranes has been suggested to be more important in the increased total peripheral resistance found in genetic hypertension. Using manipulations of ion gradients and recordings of ion currents, membrane potentials, and tension, I have found evidence for calcium regulation as the central pathophysiological mechanism in spontaneously hypertensive rats. Increased sodium pump activity, which may be a partial compensation for the increased sodium influx in hypertension, may thus be secondary to altered calcium channel regulation in hypertension. The calcium channel, and the membrane potentials governing it, seem to be the most immediately important membrane mechanisms for hypertension research.
Hypertension 1987 Nov
PMID:Vascular muscle membrane cation mechanisms and total peripheral resistance. 244 79


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