Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 40 male patients with established essential hypertension (P diastolic greater than mmHg) the density and responsiveness of platelet alpha 2-adrenoceptors and lymphocyte beta 2-adrenoceptors were measured and compared with those in 40 male age-matched normotensive subjects (P diastolic less than 90 mmHg). The mean densities of platelet alpha 2-adrenoceptors (assessed by 3H-yohimbine binding) and of lymphocyte beta 2-adrenoceptors (assessed by (+/-) 125 iodocyanopindolol binding) were significantly increased in essential hypertensive patients (P less than 0.01). If data from all 80 subjects were combined there were significant positive correlations between mean arterial blood pressure of the subjects and alpha 2-adrenoceptor density (r = 0.591, P less than 0.001) and beta 2-adrenoceptor density (r = 0.648, P less than 0.001), respectively. The increases in and beta-adrenoceptor densities in essential hypertension were accompanied by enhanced responsiveness alpha- of platelets to 10 microM adrenaline to adrenergic stimulation: the aggregatory response via alpha 2-adrenoceptor stimulation) was increased, and in lymphocytes isoprenaline (0.01 - 100 microM) produced (via adrenoceptor stimulation) greater increases in cyclic AMP at each concentration than in control. Furthermore, activation of platelet adenylate cyclase by prostaglandin E1 was exaggerated in essential hypertensive patients. It is concluded that the increased density and responsiveness of alpha- and beta-adrenoceptors in essential hypertension may reflect enhanced sympathetic activity, and may contribute to the elevation of blood pressure.
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PMID:Increased density and responsiveness of alpha 2 and beta-adrenoceptors in circulating blood cells of essential hypertensive patients. 610 Jul 31

The effects of somatostatin on plasma renin activity (PRA) and blood pressure were evaluated in patients with essential hypertension (EH) and in normotensive subjects. All subjects examined were hospitalized and placed on a diet containing 7-8 g/day sodium chloride and received an intravenous infusion of somatostatin (500 microgram/20 ml of saline, for 60 min) in the basal condition. During somatostatin infusion, the mean blood pressure (MBP) remained unaffected in all patients with EH and the normotensive subjects, while the PRA decreased slightly in the EH group. When the patients with EH were classified according to their renin levels (low, normal and high), parallel significant decreases in MBP and PRA were found only in the high renin group during the somatostatin infusion. No significant change in MBP and PRA was observed in the other groups including the normotensive subjects. To assess the activity of synthetic somatostatin, the plasma levels of growth hormone (GH) and cyclic AMP were measured. These levels were lowered significantly during the infusion and the GH levels showed a rebound 15 min after cessation of the infusion. The cyclic AMP returned to the basal levels, but no rebound was observed. The above data indicate that the fall in blood pressure in the high renin group in the basal condition was probably due in part to reduced renin release by somatostatin, and the maintenance of high blood pressure especially in high renin EH.
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PMID:Effect of somatostatin on plasma renin activity and blood pressure in patients with essential hypertension. 610 26

In order to define the alteration of the function of the adrenergic system in hypertension, we studied directly the receptor-cyclase coupling protein (N protein), which is one of the components of the enzyme adenylate cyclase. N protein was determined in erythrocyte membranes of patients with essential hypertension and normal subjects, with a complementation assay in vitro. Fifteen normal subjects and 18 patients with essential hypertension (eight untreated and ten treated with beta-adrenoreceptor blocking drugs alone or in combination with other antihypertensive drugs), and two patients with pseudohypoparathyroidism type Ia (known to have deficient N protein activity), were studied. Erythrocyte N protein activities in the various groups expressed as percentages of the means +/- SD of normals were: normal subjects 100 + 13.7, untreated hypertensive 108.9 +/- 20.4, treated hypertensive 104.3 +/- 11.3 and pseudohypoparathyroidism type Ia 43%. The difference between N protein activity in the hypertensive patients and normals was not statistically significant. We suggest that the molecular basis for the altered sympathetic responsiveness in essential hypertension may reside in other components of the cyclic AMP protein kinase effector system.
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PMID:Receptor-cyclase coupling protein in erythrocytes of patients with essential hypertension. 614 35

We studied plasma levels of cyclic nucleotides and their responses to submaximal exercise as an endogenous adrenergic stimulation in normal subjects, untreated and treated patients with essential hypertension to assess the roles of various hormones and the autonomic nervous system in essential hypertension. Plasma c-AMP level was significantly higher in untreated, diuretic-treated patients and those treated with propranolol than in normal subjects, but plasma c-GMP level was comparable in normal subjects and untreated patients. Plasma c-AMP decreased significantly, whereas plasma c-GMP increase significantly, after chronic propranolol therapy. Plasma c-AMP increased significantly after submaximal exercise in normal subjects, untreated patients and those treated with propranolol, but plasma c-GMP increased significantly only in normal subjects. The increase in plasma c-AMP was significantly higher in untreated patients than in normal subjects and patients treated with propranolol. Moreover, the percent increase in plasma c-AMP was significantly higher in untreated patients than in those treated with propranolol. Therefore, it is suggested that the sympathetic nervous system may be hyperactive, and that a hyperreactivity of the beta-adrenergic receptors may play an important role in essential hypertension.
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PMID:Plasma levels of cyclic nucleotides in patients with essential hypertension. 625 42

The effect of standing and physical exercise and catecholamines and cyclic nucleotides in plasma was measured in 8 patients with essential hypertension under standardized conditions before and after prolonged treatment with clonidine. Before clonidine medication noradrenaline, adrenaline and cyclic AMP (cAMP) increased in response to standing and bicycling for 20 min. No significant correlation was found between their absolute levels nor was the increase in cAMP following exercise correlated to the increase in noradrenaline. Standing and physical exercise were without effect on cyclic GMP (cGMP). Clonidine reduced the plasma noradrenaline concentration in supine position and the noradrenaline and the adrenaline response to standing and exercise. Plasma cAMP was uneffected by clonidine under basal conditions but the response to exercise was slightly reduced initially. During clonidine there was a positive correlation between the plasma levels of cAMP and noradrenaline following work. Clonidine produced an increase in plasma cGMP in supine position, immediately prior to bicycling and after 5 min of exercise.
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PMID:Plasma cyclic nucleotides and plasma catecholamines before and after prolonged treatment with clonidine in hypertensive patients. 626 88

To investigate the impairment of beta-adrenoceptor responsiveness in human hypertension, we evaluated the effect of an oral salt load (400 mEq/day of NaCl for 7 days) on plasma catecholamine concentrations and beta-adrenoceptor-mediated effects in 11 young patients with mild essential hypertension. Responses of heart rate and plasma cAMP to isoproterenol administration were used as indices of beta-adrenoceptor responsiveness. Salt loading induced a significant reduction in the dose of isoproterenol required to raise the heart rate by 25 bpm (CD25) (from 7.6 +/- 1.5 to 5.3 +/- 0.9 micrograms, p less than 0.05) and an increase in the slopes of the regression lines for heart rate changes and isoproterenol doses (delta HR/IS) (from 3.3 +/- 0.6 to 4.7 +/- 0.7, p less than 0.05) and for plasma cyclic AMP (cAMP) level changes and isoproterenol doses (delta cAMP/IS) (from 0.3 +/- 0.06 to 1.4 +/- 0.3, p less than 0.05). After salt loading there was a significant reduction in plasma catecholamine concentrations with a significant relationship between changes in upright plasma epinephrine levels and changes in CD25 (r = 0.904, p less than 0.01) and in the slopes for delta HR/IS (r = 0.983, p less than 0.001) and delta cAMP/IS (r = 0.922, p less than 0.001). These results support the hypothesis that the impairment of beta-adrenoceptor sensitivity observed in human hypertension is associated with a beta-adrenoceptor overstimulation due to chronically elevated adrenergic tone.
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PMID:Studies of the mechanisms underlying impairment of beta-adrenoceptor-mediated effects in human hypertension. 630 32

Investigations in numerous laboratories have characterized a salt transport system, present in many animal cell types, which catalyzes the transmembrane transport of NaCl and KCl in a tightly coupled process. The system is inhibited by loop diuretics such as furosemide and bumetanide. This transport system has been designated the loop diuretic-sensitive NaCl/KCl symporter. It has been implicated in transepithelial salt secretion and absorption as well as in cell volume regulation, and it may be defective in patients suffering from essential hypertension. This review serves to evaluate research conducted to date regarding the mechanism, mode of regulation, and physiological significance of the transport system. Ion binding specificities and absolute binding constants for all three naturally occurring ions have been determined in one cell system, the MDCK kidney epithelial cell line. In that same cell line, substrate binding was shown to exhibit apparent cooperativity. although a few reports suggest unidirectional transport of ions via this system under certain conditions, the consensus of reports indicates fully reversible, bidirectional salt transport with the direction of net flux determined by the magnitudes of the gradients of the three transported ions. Growth of cells in media containing a low concentration of K+ (less than 0.25 mM) allows selection of mutants lacking or defective in the symporter. Kinetic analyses with the MDCK cell line have shown that the symporter catalyzes accelerative exchange transport. However, exchange transport of one ion in the absence of one of the other two ionic substrates has not been documented. Comparison with other well-characterized transmembrane transport systems has shown that the characteristics of the NaCl/KCl symporter most resemble those of two-species facilitators (chemiosmotically-coupled symporters) found in prokaryotes and eukaryotes alike. these two-species facilitators consist of a single transmembrane protein and may function by a carrier-type mechanism as originally proposed by Peter Mitchell. A molecular model for the NaCl/KCl symporter is presented and discussed. Activation of symport activity requires ATP and probably occurs by a protein kinase-catalyzed mechanism. In some cell types activation is cyclic AMP dependent. ATP hydrolysis is not stoichiometric with transport. Phosphorylation of an integral membrane protein with an apparent size of 240 000 daltons correlates with activation of transport. It is postulated that this protein is the loop diuretic-sensitive NaCl/KCl symporter.
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PMID:Mechanism, regulation and physiological significance of the loop diuretic-sensitive NaCl/KCl symport system in animal cells. 632 61

These studies were undertaken to clarify the role of the central and peripheral sympathetic nervous system and the renin-aldosterone system on the onset and maintenance of high blood pressure in essential hypertension (EH), and the following examinations were performed: 1) Urinary free norepinephrine and epinephrine excretion (UNEf and UEf), urinary conjugated norepinephrine and epinephrine excretion (UNEconj and UEconj), plasma norepinephrine and epinephrine concentration (PNE and PE), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in 52 patients with EH, who were divided into two groups (borderline EH: b-EH, and sustained EH: s-EH), and fifteen normals (N). 2) Cardiac index (CI), total peripheral resistance index (TPRI), appearance time, mean transit time and stroke index (SI) were determined by the dye-dilution method in eight patients with b-EH, ten patients with s-EH and ten N. 3) Clonidine was administered orally in a single dose of 150 micrograms to seven patients with s-EH and three patients with b-EH, and PNE, PE and growth hormone (GH) were measured before and after the administration. 4) Isoproterenol was infused intravenously in a dose of 0.02 microgram/kg/min for 30 min to 18 patients with s-EH and six N, then plasma cyclic AMP (c-AMP) and PRA were determined before, during and after the infusion. 5) Methacholine was injected intramuscularly in a dose of 10 mg to seven N, and PNE, PE and PRA were measured before and after the injection. There were no significant differences of PNE, PE, UNEf and UEf among the three groups (b-EH, s-EH and N), but UNEconj in both b-EH and s-EH was higher than in N (b-EH: p less than 0.1, s-EH: p less than 0.05). PRA in s-EH was slightly lower not only in N but also in b-EH. PAC in b-EH and s-EH was slightly lower than in N. The difference of PAC between b-EH and s-EH was not found. CI and SI were higher than in N (p less than 0.05), but TPRI was normal. In s-EH, TPRI was slightly elevated as compared with b-EH (p less than 0.1). In s-EH, clonidine caused a significant lowering of both blood pressure and PNE with a simultaneously marked increment of GH; on the other hand, in b-EH blood pressure and PNE did not change significantly in spite of the distinct rise of GH. After the isoproterenol infusion, PRA and c-AMP increased, and there was a significant correlation between the initial level of PRA and the maximal increment of PRA after the infusion in both s-EH and N.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Studies on the role of the central and peripheral sympathetic nervous system and the renin-aldosterone system on the onset and maintenance of high blood pressure in essential hypertension]. 632 58

beta 2-Adrenoceptor function may be decreased in primary hypertension, resulting in increased peripheral resistance. To study the beta 2-adrenoceptor function, we used circulating mononuclear leukocytes (MNL) as a model system. Twenty untreated hypertensive subjects [(HT) 10 men and 10 women] and 20 age- and sex-matched healthy normotensive (NT) volunteers were studied. The beta 2-adrenoceptor density was not significantly different between HT and NT, but the dissociation constants for the high- and low-affinity agonist binding states, studied by isoprenaline competition assays, were significantly higher in HT. Stimulation of adenylyl cyclase with isoprenaline (10 microM, beta 2-adrenoceptor-mediated stimulation) was not significantly different between the two groups. Forskolin-mediated direct stimulation of adenylyl cyclase was significantly higher in women than in men. For both sexes, the forskolin-induced cyclic AMP production was lower in the HT group, reaching statistical significance in the men. No major abnormalities were observed in beta 2-adrenoceptor function in mononuclear leukocytes. The putative relation between the decreased forskolin-mediated adenylyl cyclase activity and primary hypertension requires further study.
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PMID:Forskolin-stimulated adenylyl cyclase activity is decreased but beta 2-adrenoceptor function is unchanged in primary hypertension. 750 20

Sympathetic neural activation of vascular smooth muscle beta-receptors induces membrane hyperpolarization and arterial relaxation. This response, which likely is mediated by the Gs protein-adenylyl cyclase-cyclic AMP signaling cascade, is reduced in some hypertensive animal models and in human essential hypertension. Since reduced beta-receptor-mediated vasodilation is a potential mechanism for enhanced arterial resistance, this study was designed to identify which step (or steps) in the beta-receptor signaling cascade is altered in hypertension. Transmembrane potentials were recorded in situ in small first-order arterioles and venules of cremaster muscle from hypertensive, reduced renal mass rats and normotensive, sham-operated controls. Vascular muscle cells in arterioles and venules of hypertensive rats were 5-7 mV more depolarized than in respective vessels of control rats during superfusion with physiological salt solution. Hyperpolarization and depolarization responses were reduced in hypertensive rats during superfusion with a beta-receptor agonist and antagonist, respectively, suggesting attenuated beta-receptor responsiveness compared with normotensive rats. Furthermore, direct activation of Gs protein by 10 ng/mL cholera toxin did not affect arterial or venous transmembrane potential in hypertensive rats, but hyperpolarized arterial and venous vascular muscle in normotensive controls by 17 mV. However, when the Gs protein-adenylate cyclase coupling step of the beta-receptor cascade was bypassed by using 10(-5) M forskolin to directly activate adenylate cyclase, arterial and venous vascular muscle of hypertensive rats hyperpolarized by 25-27 mV.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered beta-receptor control of in situ membrane potential in hypertensive rats. 809 44


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