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)

1. A pulmonary chemodectoma/glomangiosarcoma that had metastasized from the thigh was studied after removal from a 22 year old Algerian patient with hypertension, high plasma prorenin and signs of secondary aldosteronism. 2. Renin and renin mRNA were localized in sections of the tumour tissue using monoclonal anti-human renin antibody and human renin cDNA probe, respectively. 3. The cells grew prolifically in culture, but, even though their renin content was similar to that of transfected human juxtaglomerular cell tumour cells (approximately 1 pg/microgram DNA), their rate of secretion of renin was much lower (0.05-0.15 cf. 0.5-1.5 pg/h per microgram DNA). 4. Forskolin (10 mumol/l for 24 h) increased secretion of renin from 1.9 +/- 0.36 to 4.1 +/- 0.64 pg/ml per h of culture (P less than 0.001, n = 11), consistent with cAMP being a second messenger in the secretory mechanism. 5. The cells should provide valuable information about intracellular mechanisms for the regulation of renin synthesis and secretion.
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PMID:Renin secretion from malignant pulmonary metastatic tumour cells of vascular origin. 282 9

The quantitatively most important noradrenergic cell group of the brain is the locus coeruleus. Significantly increased cAMP concentration could be measured in spontaneously hypertensive rats in comparison to normotensive Wistar-Kyoto control rats at every stage investigated. Furthermore, both the basal activity and maximal stimulation of Ca++- and GTP-dependent adenylate cyclase as well as phosphodiesterase activity were significantly decreased in the spontaneously hypertensive rats at 14 weeks of age. The possible role of the locus coeruleus in spontaneous hypertension is presumed in counterregulatory mechanisms against rising blood pressure.
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PMID:Alterations in the adenylate cyclase-cAMP-phosphodiesterase system in the locus coeruleus during the development of spontaneous hypertension of the rat. 283 Apr 11

The deoxycorticosterone acetate (DOCA)-Na model of hypertension requires the presence of vasopressin for expression of high blood pressure. In the present study, the effects of vasopressin V2-receptor stimulation were examined in kidneys from rats receiving 1 wk of DOCA-Na or control (olive oil-tap water) treatment. The dose response to vasopressin (10(-10) to 10(-6) M) was tested in microdissected cortical collecting tubule (CCT) segments and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was significantly increased in segments from DOCA-Na rats vs. controls, confirming our previous study. In other experiments, kidneys from DOCA-Na and control rats were perfused with a modified Krebs-Henseleit buffer (37 degrees C, pH 7.4) and treated with either vehicle or 0.21-2.1 pM 1-desamino-8-D-arginine vasopressin (DDAVP). DDAVP caused significant (P less than 0.05) dose-related reductions in urine excretion (UV) and urinary sodium excretion (UNaV) in both DOCA-Na and control kidneys in the absence of changes in renal hemodynamics. However, DDAVP produced earlier and significantly greater reductions in UV and UNaV in kidneys from DOCA-Na vs. control rats. Percent fractional excretion of sodium was reduced significantly only in the DOCA-Na group (2.1 pM DDAVP). A small degree of antikaluresis was seen with DDAVP in both groups. Thus, DOCA-Na treatment augmented cAMP accumulation in the CCT, accompanied by a significant enhancement of DDAVP-stimulated urinary sodium and water reabsorption at the level of the intact kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhanced vasopressin (V2-receptor)-induced sodium retention in mineralocorticoid hypertension. 283 67

The parotid excretion of cAMP was measured in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in this study. In addition, adenylate cyclase activity in parotid gland tissue was determined. The cAMP excretion rate was increased immediately after isoproterenol infusion. This elevation was more pronounced in young (6-8 weeks) than in older (16-18 weeks) animals, both in WKY and in SHR. These data demonstrate a diminished cAMP response to isoproterenol application with respect to the age of the animals. This could indicate that there is an age-dependent functional alteration of the beta-adrenoceptor-adenylate cyclase complex. In agreement with the results of these in vivo studies, the stimulation of adenylate cyclase activity of the parotid gland by isoproterenol or fluoride was enhanced in young SHR and lowered in old SHR when compared to their normotensive controls of the same age. One may conclude that the sympathetic activity is enhanced in young SHR, and that the beta-adrenoceptor system is hypersensitive to adrenoceptor agonists. This might contribute to the development of hypertension in SHR. Sixteen to eighteen weeks old SHR showed a diminished cAMP output following isoproterenol application when compared to normotensive control rats of the same age. The reduction of the response to isoproterenol stimulation in old SHR seems to be related to a reduced sensitivity to catecholamine stimulation.
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PMID:Glandular adenylate cyclase system in genetic hypertension: age-dependent response to catecholamines. 283 96

The hormone-sensitive adenylate cyclase system of plasma membrane is composed of at least three types of proteins: hormone receptors, activatory (Gs) and inhibitory (Gi) guanine nucleotide-regulatory proteins and the catalytic unit (C). Abnormal hormonal regulations of platelet adenylate cyclase in both humans and experimental animals have been reported to occur in hypertension. However, little is known about the mechanisms for these alterations. The aim of the present study was to compare the activity of C and the inhibitory capacity of Gi in platelet membranes from spontaneously hypertensive rats (SHR) and their normotensive controls (WKY). Adenylate cyclase activity of 40,000 g membranes was assessed at pH 7.5 with 0.1 mM (alpha-32P) ATP and an appropriate bivalent cation (Mn2+ or Mg2+). Under incubation conditions that uncoupled C from Gs and Gi (25 mM MnCL2, 100 microM forskolin), a significantly lower adenylate cyclase activity was measured in membranes from SHR rats (2.07 +/- 0.12 vs 2.36 +/- 0.1 nmol cAMP/mn/mg of protein, p less than 0.05). This difference between the two strains was also observed in platelet homogenates. In a second kind of experiments, membranes were incubated with 2.1 mM MgCl2 instead of MnCl2. In both strains of rats, low concentrations of Gpp (NH)p (10 to 300 nM) inhibited adenylate cyclase activity when stimulated by 50 microM forskolin. However, the maximal extent of inhibition was significantly reduced in hypertensive rats (49.7 +/- 2.4 vs 60.5 +/- 2.3 p. 100, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Anomalies of the adenylate cyclase system in platelets of the SHR rat]. 284 72

In recent research a new series of specific drugs, one of which is guanabenz (GBZ, 2,6(dichlorobenzyliden)-aminoguanidine) has been introduced into the clinical treatment of centrally mediated hypertension. Guanabenz (GBZ) is considered to be among the most specific alpha 2-adrenergic agonists, acting similarly to clonidine by decreasing the sympathetic outflow from the brain to the peripheral circulatory system. In the present report we show that GBZ displays a significant affinity for beta-adrenoceptors. In displacement studies of the iodinated beta-antagonist [125I]cyanopindolol (CYP) from turkey erythrocyte membranes, the dissociation constant of GBZ was 3.8 microM. Inhibition of the (-) epinephrine induced adenylate cyclase activity by GBZ is competitive, with an apparent dissociation constant of 30 microM. A similar value was obtained by studies of GBZ's effect on the (-) epinephrine-induced [3H]cAMP accumulation in intact turkey erythrocytes. In view of its unexpected affinity for beta-adrenoceptors, we examined the three-dimensional structure of crystalline GBZ. In these studies substantial differences between clonidine and GBZ were observed, despite their strong structural resemblance. These dissimilarities (angle of rotation phi = 39.7 degrees as compared to 76 degrees in clonidine, and the rotational restriction of clonidine as compared to the greater mobility in rotation of GBZ) could explain the difference of specificity between these two compounds.
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PMID:Beta-adrenergic activity and conformation of the antihypertensive specific alpha 2-agonist drug, guanabenz. 285 65

Twenty-five years after the discoveries of the existence of atrial granules and of volume receptors in the heart atria the search for natriuretic hormones has led to the isolation and identification of the atrial natriuretic factors (ANF) now considered as a hormonal system. These peptides are probably synthesized and stored in the Golgi apparatus of cardiac myocytes and are released in response to atrial wall stretch following acute plasma volume expansion and increased central blood volume, e.g., during head-out water immersion, in arterial hypertension, or increased left and/or right atrial pressure in cardiac failure, but also possibly in response to increased frequency of myocardial contractions, e.g. in paroxysmal tachycardia. The mechanisms of the renal action of these potent natriuretic hormones are not yet precisely known. Increased GFR may contribute to the initial rise in urinary sodium excretion and increased renal medullary blood flow to the later phase of natriuresis. The proximal tubule, the thin descending and the ascending limb of Henle's loop and especially the medullary collecting tubule were so far incriminated as tubular sites of action of ANF. Finally, recycling of sodium in medullary tissue and secretion of sodium via back-flux from the interstitium into the medullary collecting tubule are postulated to result in the hypernatric urine observed after ANF administration. Direct suppression of the secretion of renin, aldosterone, vasopressin, and vasopressin-stimulated cAMP synthesis may also contribute to its diuretic, natriuretic, and antihypertensive effects. The renal hemodynamic and tubular as well as the adrenal and systemic vascular effects are related to enhanced cGMP synthesis in medium-sized arterial vessels, in glomeruli and specific tubular segments, and in adrenal tissue, and may be calcium dependent. Specific ANF-binding sites were detected in these target organs. Although increased ANF release was observed in response to atrial distension in various disease states, which may contribute to renal sodium elimination in human hypertension and congestive heart failure, further studies are needed to identify its precise physiological and pathophysiological significance.
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PMID:Atrial natriuretic hormones--thirty years after the discovery of atrial volume receptors. 294 41

Functional modifications, such as a reduction in hormonal response, which occur in the cardiovascular system in hypertension, are reflected at the cellular level by anomalies in cyclic nucleotide and other messenger systems. To distinguish between primary and adaptive abnormalities, we pursued three research strategies. (i) Investigations on various models of hypertension. To be considered a primary defect, an abnormality should also be present in other genetically hypertensive models. Indeed, we have confirmed the occurrence of cellular hyperplasia in the heart of spontaneously hypertensive rats (SHR) as well as in spontaneously hypertensive mice (SHM). An increase of calmodulin levels in the heart and kidney is also observed in both the SHR and SHM. (ii) Studies on the evolution of hypertension with age. In humans, a decrease of cAMP levels in response to beta-adrenergic stimulation in older patients is contrasted with an excess in younger subjects. In the SHR, protein kinase activity of the heart is lower in the prehypertensive stages, whereas this defect appears much later in the aorta. (iii) Experiments on anomalies in newborns and cultured cells. The heart and kidney in the SHR exhibit significant hyperplasia at birth, and an abnormal growth continues in tissue culture. We hope that these strategies will eventually help to provide biochemical and functional markers for genetic analysis of factors which may be involved in the pathogenesis of hypertension.
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PMID:Primary versus secondary events in hypertension. 298 25

A total of 64 male patients with varying forms of coronary heart disease (CHD), aged 43 to 65 years, and free of diabetes mellitus, obesity and arterial hypertension symptoms, were studied in conditions of emotional stress simulated, using the method of mental calculations with shifts of attention under time shortage. Pre- and post-exercise blood levels of cyclic nucleotides (cAMP and cGMP), the somatotropic hormone and immunoreactive insulin were measured. Stress-induced decrease in platelet cAMP/cGMP ratios, indicative of further increase in the functional activity of platelets, was demonstrated in coronary patients with marked coronary atherosclerosis, as contrasted to normal subjects and patients with milder disease. They also showed a more considerable (sixfold) increase in the somatotropic hormone levels and a tendency to decreased levels of immunoreactive insulin under stress, apparently as a consequence of the prevailing activation of alpha-adrenoreceptor pathways.
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PMID:[Dynamics of cyclase systems and hormonal indices in patients with ischemic heart disease in a state of emotional stress]. 300 51

Variations in calcium alimentation influence the development of high blood pressure in genetic hypertensive rats. Different calcium feeding and changes in parathyroid hormone status cause altered cAMP-content in specific brain areas. All animals with high calcium diet show significant elevated cAMP-content in the locus coeruleus, irrespective of parathyroid status. These findings support the hypothesis that elevated cAMP-concentrations reflect an increased depressor activity of the locus coeruleus.
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PMID:Participation of various brain nuclei in the altered time course of genetic hypertension in SHR dependent on changes in calcium metabolism. 303 48


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