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 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years in conjunction with medicamentous treatment of renoparenchymatous hypertension in particular two problems were discussed: target blood pressure values and renoprotective effects of antihypertensive drugs. Prospective studies revealed that a blood pressure reading of < 130/80 mm Hg significantly retards the progression of nephropathy whereby patients with proteinuria > 1 g/d benefit from even lower BP readings. In diabetic nephropathy the drugs of choice are inhibitors of angiotensin converting enzyme (ACEI), already in the incipient stage and also in normotensive patients. The importance of ACEI in the treatment of non-diabetic nephropathies was confirmed recently by controlled prospective studies AIPRI and REIN. A maximal renoprotective effect of ACEI probably calls for larger doses than those needed for normalization of BP. Long-term investigations of the renoprotective effect of antagonists of angiotensin AT1 receptors and comparative studies with ACEI resp. are not available. Dihydropyridine blockers of calcium channels with a short-term action (nifedipine) may have a negative influence on the progression of diabetic nephropathy, the effect of dihydropyridines of the second generation is tested in prospective studies. Non-dihydropyridine calcium channel blockers have a renoprotective action in diabetic nephropathy. In cca two thirds of the patients combined treatment with ACEI and diuretics or with calcium channel blockers is necessary. As to other antihypertensive drugs, vasodilatating beta-blockers and perspectively antagonists of endothelin receptors are useful.
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PMID:[Treatment of renal hypertension]. 1122 86

In the rat and the rabbit, a number of studies have reported the effects of angiotensin II (ANG II) on Na(+) reabsorption by the proximal (PT) and distal (DT) convoluted tubules of the kidney. The aim of the present study was to examine the effect of ANG II on Ca(2+) uptake by the luminal membranes of the PT and DT of the rabbit. Incubation of PT and DT with 10(-12) M ANG II enhanced the initial Ca(2+) uptake in the two segments. Dose-response experiments revealed, for Ca(2+) as well as for Na(+) transport, a biphasic action with a maximal effect at 10(-12) M. Ca(2+) transport by the DT luminal membrane presents a dual kinetic. ANG II action influenced the high-affinity Ca(2+) channel, increasing maximal velocity from 0.72 +/- 0.03 to 0.90 +/- 0.05 pmol x microg(-1) x 10 s(-1) (P < 0.05, n = 3) and leaving the Michaelis-Menten constant unchanged. The effect of ANG II was abolished by losartan, suggesting that the hormone is acting through AT1 receptors. In the PT, calphostin C inhibited the effect of the hormone. It is therefore probable that protein kinase C is involved as a messenger. In the DT, however, neither Rp cAMP, calphostin C, nor econazole (a phospholipase A inhibitor) influenced the hormone action. Therefore, the mechanisms involved in the hormone action remain undetermined. Finally, we questioned whether ANG II acts in the same DT segment as does parathyroid hormone on Ca(2+) transport. The two hormones increased Ca(2+) transport, but their actions were not additive, suggesting that they both influence the same channels in the same segment of the distal nephron, i.e., the segment responsible for the high-affinity calcium channel.
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PMID:Effect of angiotensin II on calcium reabsorption by the luminal membranes of the nephron. 1135 Jul 74

Vascular structure, function, and mechanics are altered in hypertension, which contributes to an important degree to complications of elevated blood pressure. Vascular hypertrophy with collagen deposition and increased stiffness is found in large arteries, whereas in small arteries, smooth muscle cells are restructured around a smaller lumen, and there is no net growth of the vascular wall, particularly in milder forms of hypertension. Hypertrophic remodeling and increased small artery stiffness may be found in more severe hypertension. Endothelial dysfunction occurs in large or smaller vessels in a variable percentage of patients, particularly in presence of other risk factors such as diabetes, smoking, dyslipidemia, and advanced atherosclerosis. In clinical trials, 1-year treatment with angiotensin-converting enzyme inhibitors, angiotensin AT1 receptor antagonists, and long-acting calcium channel blockers corrected small artery structure and endothelial dysfunction in hypertensive patients, whereas beta-adrenergic receptor blockers did not. Improved outcomes in hypertensive patients demonstrated in recent trials with some but not others of these agents could be a consequence, at least in part, of vascular protection offered by some antihypertensive agents.
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PMID:Small artery remodeling in hypertension: can it be corrected? 1146 50

Angiotensin II (Ang II) is one of the most important vasoconstrictive hormones but is also known to act as a neuromodulator and a neurotransmitter in the central and peripheral nervous systems. In a previous study, we have shown that Ang II, via AT1 receptors, induced depolarization by inhibition of M-type K(+) channels and SK channels in submandibular ganglion (SMG) neurons. In this study, we investigated the effects of Ang II on calcium channel current (I(Ca)) in acutely dissociated SMG neurons by the patch-clamp technique using the whole-cell configuration. Ang II inhibited total I(Ca) by 32.1+/-2.7%. The half-maximum inhibitory concentration (IC(50)) of Ang II for inhibiting I(Ca) was 0.8 microM. In the presence of 1 microM losartan, which is a selective antagonist of AT1 receptors, the effect of Ang II was attenuated (7.6+/-1.5%). Application of a strong depolarizing voltage prepulse did not affect the Ang II-induced inhibition of I(Ca) (32.8+/-2.8%). Intracellular dialysis of GDP-beta-S attenuated the inhibition of I(Ca) (6.8+/-2.1%). The mean percentage inhibitions of L-, N- and P/Q-type VDCCs by Ang II were 29.1+/-1.7, 16.3+/-6.0 and 1.2+/-0.8%, respectively, of the total I(Ca).
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PMID:Angiotensin II-induced inhibition of calcium currents in hamster submandibular ganglion neurons. 1167 35

Endothelial cells produce both vasodilatating compounds as nitric oxide, prostacycline, endothelial derived hyperpolarising factor and counteracting substances known as endothelial derived contracting factors: endothelin, tromboxan A2, prostaglandin H2, free oxygen radicals. Natural balance between both groups affects blood perfusion of various tissues and constitutes important element in blood pressure control. More and more attention is paid to endothelial dysfunction in patogenesis of hypertension. In a number of studies endothelial dysfunction in hypertensive patients was found out as decreased release of nitric oxide or increased production of endothelin. Principle mechanism of impaired function of endothelium in hypertension seems to be decreased production and increased degradation of nitric oxide mainly due to free oxygen radicals. Favorable effects in improvement of endothelial function were achieved by using ACE inhibitors, AT1 receptor blockers and calcium channel antagonists.
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PMID:[Endothelial dysfunction in hypertension--clinical implications]. 1208 1

The mechanism and treatment of hypertensive systolic heart failure are not well defined. We compared the effect of an angiotensin-converting enzyme inhibitor (cilazapril, 10 mg/kg), an angiotensin receptor blocker (candesartan, 3 mg/kg), a calcium channel blocker (benidipine, 1, 3 or 6 mg/kg), and the same calcium channel blocker combined with renin-angiotensin blockers on systolic heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed an 8% Na diet from 6 weeks of age and then subjected to the above drug treatments. Benidipine (1 mg/kg), cilazapril, and candesartan had compatible hypotensive effects and similar beneficial effects on cardiac hypertrophy, gene expression, and survival rate. The combination of benidipine with cilazapril or candesartan was found to have no additional beneficial effects on the above parameters, with the exception of a reduction in atrial natriuretic polypeptide gene expression. On the other hand, candesartan normalized serum creatinine, but serum creatinine was unaffected by either benidipine at 1 or 3 mg/kg or cilazapril. Further, the combined use of benidipine and either candesartan or cilazapril resulted in an additional reduction of urinary albumin excretion in DS rats. Thus systolic heart failure in DS rats is mainly mediated by hypertension, while renal dysfunction of DS rats is due to both hypertension and the AT1 receptor itself. These findings suggest that the combination of a calcium channel blocker with an AT1 receptor blocker or ACE inhibitor may be more effective in treating the renal dysfunction associated with systolic heart failure than monotherapy with either agent alone. However, further studies will be needed before reaching any definitive conclusion on the efficacy of this combination therapy in patients with heart failure.
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PMID:Combination treatment with a calcium channel blocker and an angiotensin blocker in a rat systolic heart failure model with hypertension. 1213 27

In many types of cardiovascular pathophysiology such as hypercholesterolemia and atherosclerosis, diabetes, cigarette smoking, or hypertension (with its sequelae stroke and heart failure) the expression of endothelial NO synthase (eNOS) is altered. Both up- and downregulation of eNOS have been observed, depending on the underlying disease. When eNOS is upregulated, the upregulation is often futile and goes along with a reduction in bioactive NO. This is due to an increased production of superoxide generated by NAD(P)H oxidase and by an uncoupled eNOS. A number of drugs with favorable effects on cardiovascular disease upregulate eNOS expression. The resulting increase in vascular NO production may contribute to their beneficial effects. These compounds include statins, angiotensin-converting enzyme inhibitors, AT1 receptor antagonists, calcium channel blockers, and some antioxidants. Other drugs such as glucocorticoids, whose administration is associated with cardiovascular side effects, downregulate eNOS expression. Stills others such as the immunosuppressants cyclosporine A and FK506/tacrolimus or erythropoietin have inconsistent effects on eNOS. Thus regulation of eNOS expression and activity contributes to the overall action of several classes of drugs, and the development of compounds that specifically upregulate this protective enzyme appears as a desirable target for drug development.
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PMID:Regulation of endothelial-type NO synthase expression in pathophysiology and in response to drugs. 1238 13

Blood vessels are remodeled in hypertension both structurally and functionally. The changes that occur in their structure, mechanical properties, and function contribute to blood pressure elevation and to complications of hypertension. We studied the remodeling of small arteries in experimental animals and humans. Smooth muscle cells of small arteries are restructured around a smaller lumen, with significant remodeling of the extracellular matrix and collagen and fibronectin deposition. Interestingly, there is no evidence of net growth of the vascular wall (which results in so-called eutrophic remodeling), particularly in the milder forms of human essential hypertension. Hypertrophic remodeling and increased small artery stiffness may be found in more severe forms of hypertension. Almost all hypertensive patients have vascular structural remodeling. However, only some exhibit endothelial dysfunction. This is particularly true in mild hypertension, in which endothelial dysfunction is less common. A 1-year treatment of hypertensive patients with angiotensin converting enzyme inhibitors, angiotensin AT1 receptor antagonists, and long acting calcium channel blockers corrected small artery structure and, to variable degrees depending on the agents used, impaired endothelial function. In contrast, beta blockers did not improve structure, function, or mechanics of vessels. When beta-blocker-treated patients were switched to an AT1 receptor antagonist, small artery structure and impaired endothelial function were corrected. The vascular protective action of some antihypertensive agents may contribute to improve outcome for hypertensive patients, although this is presently unproven.
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PMID:Effect of antihypertensive treatment on small artery remodeling in hypertension. 1271 May 31

Pustular eruptions caused by anti-hypertension drugs are relatively rare. They have been reported with beta-adrenergic blocking agents, calcium channel blocker and angiotensin converting enzyme (ACE) inhibitors. Angiotensin II type 1 (AT 1) receptor antagonists, as a new class of drug for hypertension, has become an established and popular treatment. We describe a patient with generalized pustular psoriasis induced by candesartan cilexetil (AT1 receptor antagonist), who was previously diagnosed as flexural psoriasis. It is known that AT1 receptor antagonists do not increase the bradykinin level, inhibiting the renin-angiotensin system more potently than ACE inhibitor. But our results suggest that AT 1 receptor antagonists could have some ACE inhibitor potency as an up-regulator for bradykinin in our patient, with pustular eruptions developing on the psoriatic background. To the best of our knowledge, there have been no reported cases of pustular psoriasis associated with AT1 receptor antagonists.
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PMID:Candesartan cilexetil induced pustular psoriasis. 1294 27

In the period from 1990 to 2002, 201 patients with suicidal antihypertensive drugs poisoning were treated, including 138 women and 63 men from 15 to 84 (mean 36) years old. The main causes of suicides were various kinds of depression (63%) as well as psychopathy and/or sociopathy (16%) and schizophrenia (10%). Twenty eight patients attempted repeatedly to commit suicide. Thirty six persons were poisoned by only antihypertensive drugs, in 165 remaining cases intoxications were mixed including antihypertensive and other different medications. beta-blockers (38.3%), calcium channel blockers (34.8%), angiotensin converting enzyme inhibitors (24.3%) and diuretics (2.5%) were used in suicidal attempts. There were no suicidal poisonings with angiotensin II AT1 receptor antagonists, alpha 1-blockers and imidazole receptor agonists. In the examined group three patients died of cardiogenic shock, electromechanical dissociation and secondary acute respiratory failure resistant to therapy. The drugs used in these cases were propranolol, amlodipine, theophylline, captopril, doxepine, propafenone, furosemide, methimazole and alcohol. Mortality rate in antihypertensive drug poisonings was 1.5%.
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PMID:[Suicidal poisoning with antihypertensive drugs]. 1456 90


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