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

Two siblings are described with hypertension, hyperreninism, hyperaldosteronism and hypokalemia. Propranolol therapy lowered blood pressure markedly, but failed to normalize serum potassium. Indomethacin orally decreased blood pressure and normalized all biochemical abnormalities. We suggest that in these patients there exists a renin-dependent hypertension in combination with a state of hyperprostaglandinism. It is likely from our studies in these 2 patients, that the state of hyperprostaglandinism is secondary to a hypertension with increased sympathetic tone.
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PMID:Effect of indomethacin in two siblings with a renin-dependent hypertension, hyperaldosteronism and hypokalemia. 735 42

Angiotensin II (AII) was found to stimulate TGF-beta 1 gene expression in rat heart endothelial cells in a dose- and time-dependent manner. The maximal induction of TGF-beta 1 mRNA was achieved by 6 h after the addition of AII. This induction was blocked by losartan, an AT1 receptor antagonist and by calphostin C, a protein kinase C inhibitor. Addition of actinomycin D and cycloheximide abolished the induction. TGF-beta 1 promoter activities were stimulated 5-fold by AII. TGF-beta 1 secreted by the rat heart endothelial cells in response to AII was in a latent form and could be activated by mild heat treatment. These results suggest that AII stimulates TGF-beta 1 production by a protein kinase C-dependent pathway which is dependent upon de novo RNA synthesis and protein synthesis. Since endothelial cells line the blood vessels and sense the rise in AII associated with hypertension, the release of TGF-beta 1 by these cells may provide the initial trigger leading to cardiac fibrosis in angiotensin-renin-dependent hypertension.
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PMID:Angiotensin II induces TGF-beta 1 production in rat heart endothelial cells. 806 Oct 46

An analysis of the renin-secreting tumors published in the literature suggests the diagnosis of JGC tumor should be evoked systematically in a young patient with severe hypertension and hypokalemia in whom a renovascular lesion has been eliminated by arteriography. A very high PRA usually is observed and blood pressure drops during converting enzyme treatment. Under acute administration of captopril, plasma renin may or may not increase, showing the inconsistency of the secretory autonomy of the tumor. The most useful examination for the localization of the tumor is the CT scan. Excessive renin production may provoke vascular lesions, left ventricular hypertrophy, and impairment of renin function that all disappear after surgical treatment, at the time when blood pressure returns to normal. Primary reninism has great physiologic importance for the hypothesis that favors the essential role of the kidney in determining the level of blood pressure. It can be considered as a unique, purely renin-dependent form of hypertension. This syndrome has no experimental equivalent and is the most caricatural form of other renin-dependent hypertension, such as renovascular disease, and probably some other forms of essential hypertension. The discovery of a renin-secreting tumor therefore constitutes a life-saving diagnosis for the patient, a subject of reflection for the specialist, and a useful tool for studies of the general mechanisms involved in enzyme biosynthesis and tumoral endocrine cell function.
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PMID:Renin-secreting tumors. 807 Apr 21

The possibility of using KRI-1314, a new cyclohexylnorstatine derivative, as an antihypertensive drug was examined using common marmosets. KRI-1314 strongly inhibited plasma renin activity (PRA) in both humans and marmosets, with a 50% inhibitory concentration of 4.7 x 10(-9) and 6.9 x 10(-9) M, respectively. In anesthetized marmosets, the increase in both blood pressure and PRA induced by bolus intravenous injection of RH-renin (0.15 microgram/kg) was suppressed by constant intravenous infusion of KRI-1314 (0.01 and 0.1 mg/kg/min) in a dose-dependent manner. In the sustained hypertension induced by continuous intravenous infusion of RH-renin (0.1 microgram/kg/min), a dose-dependent hypotensive response was produced by bolus intravenous injection of KRI-1314 (0.03-3 mg/kg). In the sodium-depleted model, whose PRA was increased by a two-week low-sodium diet coupled with furosemide loading, both intravenous injection (0.1-3 mg/kg) and oral administration (10 and 30 mg/kg) of KRI-1314 to anesthetized and conscious animals, respectively, lowered blood pressure dose-dependently with PRA suppression. The hypotensive activity of orally administered KRI-1314 (30 mg/kg) was almost equal to that of orally administered captopril (1 mg/kg). KRI-1314 did not affect heart rate in any of the experiments. These results indicate that the potent human renin inhibitor KRI-1314 may become an orally effective drug for treating renin-dependent hypertension.
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PMID:[Hypotensive action of human renin inhibitor KRI-1314 in the common marmoset]. 817 79

Hypertension arising from retained native kidneys complicates the management of recipients of renal transplants. Reluctance to administer angiotensin-converting enzyme inhibitor (ACEI) drugs to patients taking cyclosporine has reopened the question of performing native nephrectomies for poorly controlled, renin-dependent hypertension. We report the first published cases of simultaneous bilateral laparoscopic nephrectomies in 2 patients: 1 in preparation for living-related donor transplantation and the other ten months following cadaver transplantation in a patient whose end-stage renal disease was from malignant nephrosclerosis. Both had very severe hypertension resistant to multiple drugs and both became normotensive with little or no antihypertensive medication following nephrectomies. A bilateral nephrectomy is currently feasible using a laparoscopic approach.
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PMID:Laparoscopic bilateral nephrectomy for renin-mediated hypertension. 819 54

To examine the utility of rats transgenic for human angiotensinogen in the study of human renin-induced hypertension, we first developed assays to measure both the human and rat renin-angiotensin systems in these rats. We used human and mouse renin, transgenic human angiotensinogen, and the human renin inhibitor Ro 42-5892 to determine human- and rat-specific plasma angiotensinogen concentrations, renin activity, and renin concentration. The assays were validated with rat and human plasma mixed in known amounts and with plasma from rats transgenic for human renin. We then tested the human angiotensinogen-transgenic rats by infusing recombinant human renin over 10 days (50 ng/h, n=4) with osmotic minipumps. High human angiotensinogen transgene expression was found in the liver, brain, kidney, gastrointestinal tract, and aorta, whereas rat angiotensinogen gene expression was detected in the liver and brain. During human renin infusion, blood pressure increased to >200/150 mm Hg. Before infusion, human angiotensinogen was 100-fold greater than rat angiotensinogen (141 +/- 73 versus 1.2 +/- 0.16 microg angiotensin l/mL); the relation was not changed by renin infusion. Plasma renin activity increased 300-fold; human plasma renin concentration increased to very high levels (449 +/- 262 ng of angiotensin I per mL per hour), whereas rat plasma renin concentration decreased to undetectable levels. Thus, chronic human renin infusion resulted in severe hypertension with extreme plasma renin activity and plasma renin concentration. However, even at these levels, human angiotensinogen was not rate limiting and angiotensin II was not a significant stimulus for angiotensinogen production. We conclude that these transgenic rats represent a novel model of human renin-dependent hypertension.
Hypertension 1996 Mar
PMID:Human renin-dependent hypertension in rats transgenic for human angiotensinogen. 861 99

We have generated a transgenic model consisting of both the human renin and human angiotensinogen genes to study further the role played by the renin-angiotensin system in regulating arterial pressure. Transgenic mice containing either gene alone were normotensive, whereas mice containing both genes were chronically hypertensive. Plasma renin activity and plasma angiotensin II levels were both markedly elevated in the double transgenic mice compared with either single transgenic or nontransgenic controls. The elevation in blood pressure caused by the human transgenes was independent of the genotype at the endogenous renin locus and was equal in mice homozygous for the Ren-1c allele or in mice containing one copy each of Ren-1c, Ren-1d, or Ren-2. Chronic overproduction of angiotensin II in the double transgenic mice resulted in a resetting of the baroreflex control of heart rate to a higher pressure without significantly changing the gain or sensitivity of the reflex. Moreover, this change was not due to the effects of elevated pressure itself since angiotensin-converting enzyme inhibition had minimal effects on the baroreflex in spontaneously hypertensive BPH-2 control mice, which exhibit non-renin-dependent hypertension. This double transgenic model should provide an excellent tool for further studies on the mechanisms of hypertension initiated by the renin-angiotensin system.
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PMID:Chronic hypertension and altered baroreflex responses in transgenic mice containing the human renin and human angiotensinogen genes. 861 28

Arterial hypertension is frequent among chronically dialyzed patients. The kidney obviously plays a major role in arterial blood pressure control. There is a large number of experimental data emphasizing different factors (in addition to renin important in renal hypertension prognosis) such as: sodium balance, angiotensin, etc [1-8]. Sympathetic activity disorders or lack of vasodilatory prostaglandins and quinine may also play a certain role. In uremic patients peripheral arteriolar resistance is increased, unlike normotensive uremic patients or those who prove to be normotensive upon clinical examinations [8, 11-15]. Hypertension occurs in approximately 80% of patients with chronic renal failure, producing a number of complications primarily affecting the CNS and systemic circulation [5-8, 10, 11, 13]. The study concerned patients on chronic dialysis, with a male to female ratio of 69.9%:32.1%. In most of them the underlying disease, which caused chronic renal failure, was glomerulonephritis (60.0%), then pyelonephritis (17.0%) and nephrosclerosis, nephrolithiasis, polycystic kidney and, finally, renal tumours. The effect of permanent haemodialysis during the first year of treatment, was efficacious on hypertension in 1704 (65.1%) patients; in 672 (25.7%) patients therapeutical effects were achieved by dialysis and antihypertensive drugs, while in 240 (9.2%) subjects there was no improvement. General observations suggest that two types of arterial hypertension persisted in patients with chronic renal failure: volume-dependent arterial hypertension which is more frequent (90-95%) among haemodialyzed patients and renin-dependent hypertension. Such findings are of utmost importance indicating that hypervolaemia is one of the major factors in the development of arterial hypertension in patients with chronic renal failure, with renin playing the secondary role. Salt-free diet should be used in the treatment of arterial hypertension for years, a well conducted haemodialysis is highly effective in the control of arterial hypertension among these patients. In our series of patients dialysed three times a week; normalization of blood pressure was faster with lower incidence of hypertensive crises during haemodialysis and with few complications. Water and sodium excess was reduced by frequent haemodialyses and sudden changes in electrolyte, hydrostatic and other metabolic effects were minimized. Increased values of plasma renin activity were observed in a small number of patients. Ultrafiltration is insufficient for normalization of blood pressure. Hypertensive crises were frequent in these patients. Their response to medicaments such as methyldopa, beta-adrenergic blockers or other antihypertensive drugs, was good. Severe changes in blood vessels, especially in fundus oculi blood vessels were frequent in these patients. The life of hypertensive glomerulonephritis patients was especially endangered (graphs 1-6). In addition to the mentioned factors arterial hypertension during haemodialysis may also be of cardiac origin, including increase in cardiac output due to arteriovenous anastomosis, disequilibrium syndrome, changes in osmotic gradient of both extra- and intracellular spaces with resultant arteriolar wall oedema, erythrocyte amount, hypoxia, composition of dialysis fluid (sodium concentration), plasma osmotic pressure, metabolic acidosis and other factors. More recently, natriuretic hormone has also been indentified as a cause of vascular refraction. Peripherial arteriolar resistance as a cause of arterial hypertension among uremic patients must not be forgotten, because the genesis of arterial hypertension in patients with chronic renal failure is multifactorial. The highest percentage refers to volume-dependent arterial hypertension, whereas the percentage of other aetiologic factors is lower. Haemodialysis enables the normalization of blood pressure in most of hypertensive patients.
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PMID:[Arterial hypertension in patients on chronic hemodialysis]. 910 57

The depressor effect by oral calcium supplementation is known to be more pronounced in salt-dependent than in renin-dependent hypertension. This study was conducted to investigate the role of central calcium on two different pathophysiologic subtypes of experimental hypertension; (a) salt-dependent, deoxycorticosterone acetate-salt hypertensive rats (DOCA), and (b) renin-dependent, 2-kidney, 1 clip (2-K, 1C) hypertensive rats. In DOCA (n = 10), high-calcium solution (Ca+2, 65.2 mM, 10 microl) given centrally (i.c.v.) elicited a marked decrease in mean blood pressure (MBP; 170 +/- 4 to 138 +/- 5 mm Hg, p < 0.01) with a decrease in heart rate (HR; 390 +/- 18 to 344 +/- 17 beats/min, p < 0.05) lasting for 40 min. In 2-K, 1C (n = 10), high-Ca2+ i.c.v. showed a lesser decrease in MBP (178 +/- 4 to 171 +/- 5 mm Hg) and HR (419 +/- 10 to 395 +/- 12 beats/min) with shorter duration (for 20 min) than in DOCA. This significant depressor and bradycardic response to Ca2+ i.c.v. observed in DOCA was dose dependent at Ca2+ concentrations between 65.2 and 130.4 mM. In DOCA, high Ca2+ i.c.v. reduced the plasma noradrenaline (Nad) concentration significantly (479 +/- 81 to 319 +/- 62 pg/ml, p < 0.05). These results suggest that central Ca2+ plays a more important role in regulating sympathetic nerve activity and BP in salt-dependent than in renin-dependent experimental hypertension.
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PMID:Enhanced depressor effect of centrally administered high-calcium solution in salt-loaded experimental hypertension. 923 56

We have recently reported in normal isolated-perfused rat lungs that low basal tone appears to be regulated by nitric oxide (NO)-dependent and -independent mechanisms of soluble guanylate cyclase activation. In this study, we examined the role of NO in the regulation of pulmonary artery (PA) tone from rats with renin-dependent hypertension. Rats were made hypertensive by ligating the abdominal aorta above the left and below the right renal artery (aortic coarctation, AC). Mean arterial pressure significantly increased from 119 +/- 8.4 mmHg in control animals to 156 +/- 15 mmHg 7-14 days after AC surgery. PA pressures, however, remained unchanged (8.5 +/- 3.4 mmHg in control animals vs. 11 +/- 3.3 mmHg in AC animals). Hypoxic contractions in U-46619 precontracted isolated small PA (160-260 microns diameter) were significantly increased from 51 +/- 13 mg in the control group to 142 +/- 38 mg (P < or = 0.05) in AC animals. Nitro-L-arginine (NLA; 100 microM) contractions were also enhanced in the AC animal. The enhanced NLA response may correlate with an increase in endothelial cell NO synthase (NOS) as detected by Western blotting (132 +/- 28% of control; P < 0.05). These data suggest that, in this renin-dependent model of systemic hypertension, there is increased endothelial cell NOS activity that maintains low PA tone, preventing the lung from developing increased pressures.
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PMID:Peripheral hypertension and alterations in pulmonary vascular regulation. 925 47


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