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

The pathogenesis of hypertension in haemodialyzed uraemic patients is multifactorial. The following are involved: sodium and water retention as a result of the impaired excretory capacity of the kidneys, excessively increased activity of the RAAS and sympathetic nerve, increased levels of the vascular constrictor endothelin-1, cumulation of endogenous inhibitors of NO synthesis and reduced formation of vasodepressor factors. As to other factors in the development of hypertension raised intracellular calcium associated with hyperparathyroidism may participate, the stiffness of calcified arteries, erythropoietin treatment and preexisting essential hypertension. Treatment comprises salt restriction below 5 g/day, systematic control of the volume of extracellular fluid by ultrafiltration during every haemodialysis to the level of so-called dry weight and pharmacological treatment in patients where volume control dos not suffice. All drug groups are used. In their selection contraindications are taken into consideration as well as co-morbidity, the dialyzability of antihypertensive drugs and compelling evidence. In patients with a preserved residual diuresis furosemide is administered--125-750 mg/day. Beta-blockers are indicated in patients with IHD, in particular after IM. Calcium blockers are recommended in ventricular hypertrophy and diastolic dysfunction, when beta-blockers are contraindicated and in elderly patients. ACEI indicated in congestive heart failure and left ventricular hypertrophy with systolic dysfunction. Inhibitors of AT1 receptors are an alternative in case of undesirable effects od ACEI. Alpha-blockers and central alpha agonists are used mainly in combinations. In case of failure the haemodialyzation method can be altered or changing the patients to CAPD may be considered. The relationship between BP and the survival of haemodialyzed patients is bimodal. An adverse effect is exerted by a high as well as low BP and in particular by interdialyzation hypotension. The target BP for the haemodialyzed population has not been defined so far. There is, however, evidence that a high BP is independently associated with the de novo development of IHD and MAP above 106 mm Hg with de novo development of cardiac failure. MAP below 98 mm Hg minimalizes the development and progression of left ventricular hypertrophy and MAP below 106 mm Hg the development of heart failure. Long-term survival for 15 and more years is statistically significantly associated with MAP lower than 99 mm Hg.
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PMID:[Hypertension in hemodialyzed uremic patients]. 1095 54

Epidemiological evidence suggests that reducing blood pressure alone in hypertensive patients delays the onset of cardiovascular events without necessarily preventing the progression of chronic target-organ disease, such as end-stage renal failure and heart failure. Successful clinical management of hypertensive patients will therefore not be possible unless therapies are aimed both at the effective control of blood pressure and at the preservation of target-organ function. The new angiotensin II type I (AT1) receptor blocker candesartan cilexetil has been shown to be effective in reducing target-organ damage in animal models of hypertension, even at doses that do not produce significant reductions in blood pressure. Protective effects of candesartan cilexetil towards the heart and kidney have also been demonstrated in the clinical studies that have been conducted to date. Thus, candesartan cilexetil has been shown to induce regression of left ventricular hypertrophy within 8-12 weeks of treatment and to improve renal haemodynamics, both acutely and after 6 weeks of treatment in hypertensive patients. Furthermore, in hypertensive patients with co-existent non-insulin-dependent diabetes mellitus and microalbuminuria, 12 weeks of treatment with candesartan cilexetil, 8-16 mg, significantly reduced urinary albumin excretion. Clinical evidence is therefore accumulating that the antihypertensive efficacy and tolerability profile already established for candesartan cilexetil is combined with the renal and cardioprotective effects necessary for optimal management of hypertension.
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PMID:Preserving target-organ function with candesartan cilexetil in patients with hypertension. 1105 35

AT1 receptor antagonists control blood pressure (BP) effectively and reduce left ventricular hypertrophy in patients with essential hypertension. Because left ventricular hypertrophy is very common in renal transplant recipients, we examined the cardiovascular effects and the safety profile of the AT1 receptor antagonist losartan in hypertensive renal transplant recipients. In 20 renal transplant recipients with stable renal graft function 50 mg of losartan was added to the preexisting antihypertensive treatment (no angiotensin-converting enzyme inhibitors) at least 6 months after renal transplantation. Twenty-four-hour ambulatory BP, two-dimensional-guided M-mode echocardiography, and duplex sonography, as well as renal function, red blood cell count, cyclosporine A and FK 506 levels, erythropoetin, and angiotensin II concentration were determined at baseline and after 6 months of therapy. With 24-h ambulatory BP measurement, systolic blood pressure (SBP) was reduced by 7.5 +/- 2.4 mm Hg and diastolic blood pressure (DBP) by 4.5 +/- 1.8 mm Hg (P < .01 and P < .05, respectively). Posterior, septal, and relative wall thickness decreased by 0.95 +/- 0.2 mm, 0.91 +/- 0.2 mm and 0.04 +/- 0.01 mm, respectively (all P < .001). Left ventricular mass index decreased by 18.1 +/- 4.7 g/m2 (P < .01). Ejection fraction and midwall fractional fiber shortening as systolic parameters and the relation of passive-to-active diastolic filling of the left ventricle were unaltered. Serum creatinine and cyclosporine A concentration remained stable in all patients. Hemoglobin and hematocrit decreased by 1.0 +/- 0.3 g/dL and 3.6% +/- 0.9%, respectively (P < .002 and P < .001) without a change in serum erythropoetin level. In renal transplant recipients the AT1 receptor antagonist losartan reduces left ventricular hypertrophy without altering systolic or diastolic function. It is safe with regard to renal function and immunosuppression, but slightly decreases hemoglobin level.
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PMID:Regression of left ventricular hypertrophy by AT1 receptor blockade in renal transplant recipients. 1113 Jul 74

Sympathetic activity is modulated by angiotensin II (AII), both at pre- and postsynaptic level in the rat caudal artery. In the spontaneously hypertensive rat (SHR), this artery receives more dense sympathetic innervation than blood vessels of normotensive strains. This fact seems to be linked to the enhanced pressor responses elicited by noradrenaline in SHR. In this work we describe, in the SHR, the effect of a chronic treatment with the angiotensin II AT1-receptor antagonist, losartan, in modulating noradrenergic mechanisms involved in caudal artery contraction. The effect of losartan is compared to that of captopril, given at doses leading to a similar decrease of both arterial blood pressure and left ventricular hypertrophy. The contractile response of caudal artery rings induced by endogenous noradrenaline released by low frequency transmural nerve stimulation (TNS) has been studied. Under our conditions, TNS (0.5-1 Hz) induced higher contractile responses in SHR treated with losartan than in the control and captopril-treated groups. This difference seems to be due to an increase of the postsynaptic effect of noradrenaline (NA) rather than to an increase of noradrenaline release from sympathetic endings, since i) DE50 value for NA was lower in losartan-treated SHR than in the other groups, and ii) AII induced a dose-dependent increase of TNS-evoked release of radioactivity from caudal artery segments loaded with [3H]-NA, in both control and captopril-treated groups but had no effect in the losartan-treated group. These results show that chronic treatment with losartan, although slightly enhancing the pressor effect of NA at postsynaptic level, fully supresses the facilitatory role of AII on NA release.
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PMID:Chronic losartan treatment decreases angiotensin II-mediated facilitation of noradrenaline release in the caudal artery of spontaneously hypertensive rats. 1119 22

The management of diabetic hypertension requires meticulous selection of agents in the antihypertension armamentorium. There may be several associated factors to be considered while treating a hypertensive diabetic. These include hyperglycemia, dyslipidemia, proteinuria, left ventricular hypertrophy and heart failure to name a few. Losartan is the first of a new class of agents in the list of antihypertensive drugs. By its selective angiotension II receptor (subtype AT1) blocking action it is postulated to bring about a more complete inhibition of the renin-angiotensin system. Thus, it might produce all the benefits of angiotensin converting enzyme (ACE) inhibitor therapy with the freedom from cough so commonly seen with the use of ACE inhibitors. This review attempts to analyze the possible benefits of losartan therapy in diabetes.
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PMID:Role of losartan therapy in the management of diabetic hypertension. 1127 47

The ARBs are a new class of drugs with broad therapeutic potential in cardiovascular disease. These agents act by selectively inhibiting the AT1 subtype of the angiotensin II receptors. They are effective antihypertensive agents with promise, theoretically, in the prevention and regression of ventricular hypertrophy. They are safe and well tolerated in patients with CHF and might be effective in improving survival and reducing morbidity. ARBs also might have a similar role in improving the clinical outcomes of patients with coronary artery disease and chronic nephropathy. Their precise role in the treatment and prevention of cardiovascular and renal disease should be established by several ongoing clinical trials.
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PMID:Expanded role for ARBs in cardiovascular and renal disease? Recent observations have far-reaching implications. 1131 62

Using reverse transcriptase-polymerase chain reaction (RT-PCR) the changes of the angiotensin II receptor subtype 1-a (AT1a) and 1-b (AT1b) mRNA levels were examined in hypertrophied ventricles caused by ventral aorta-caval fistula of SD rats. The results show as follows. (1) Three days after operation, the ventricular weight increased significantly, whereas the level of AT1a and AT1b mRNA in both ventricles remained unchanged. (2) Twelve days after operation, the weight increase of both ventricles was more evident, the levels of AT1a and AT1b mRNA in the right ventricle increased (by 62.6% and 72.0%), as compared with control. In the left ventricle, on the other hand, the level of AT1a mRNA increased by 79.0%, while the level of AT1b mRNA showed no obvious increase. (3) Thirty-five days after operation, the levels of AT1a and AT1b mRNA in both ventricles increased still more significant, (i.e., 70.0% and 83.9% in the right and 96.5% and 86.9% in the left). Moreover, 12 d and 35 d after operation, the level of AT1a mRNA was higher than that of AT1b mRNA in both ventricles. (4) There was a positive correlation between the degree of ventricular hypertrophy with the level of AT1 mRNA in ventricular myocardium (r = 0.6168-0.8223). The results suggest that the increased mRNA expression of AT1 in myocardial hypertrophy caused by volume overload may be a mechanism underlying the increased responsiveness of hypertrophic myocardial cells to Ang II, and a difference in the expression between AT1a and AT1b mRNAs in myocardial hypertrophy may be related to the different physiological or pathophysiological roles of Ang II, mediated by the two subtypes of AT1.
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PMID:[Dynamic changes of angiotensin II type-1 receptor mRNA expression in volume-overloaded ventricular hypertrophy]. 1132 71

The pathogenetic mechanisms leading to progression of renal failure are only partly understood. Several studies in immune- and non-immune-mediated models of renal damage have recently implicated the endothelin (ET) system as a major player in these processes. In animal models, ET receptor antagonists have been shown to be highly effective in abrogating the progression of renal failure. Furthermore, cardiac structural alterations seen in hypertension and/or renal insufficiency, e.g. left ventricular hypertrophy, thickening of intramyocardial arterioles, and the increase in non-vascular interstitial tissue, are largely prevented by ET receptor antagonists. In this context it is of interest that these beneficial renal and cardiac effects are, at least in most studies, independent of systemic blood pressure. In addition to the specific pharmacological blockade of the renin-angiotensin system [ACE inhibitors, angiotensin II receptor (AT1) antagonists], blockade of ET receptors or ET converting enzyme (ECE) may be a new tool to interfere with progression of renal failure and cardiovascular remodeling in humans.
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PMID:Endothelin in renal diseases and cardiovascular remodeling in renal failure. 1133 85

Current management guidelines in hypertension define the magnitude of blood pressure lowering required from antihypertensive therapy to favourably alter cardiovascular prognosis. In addition, however, the manner in which blood pressure is reduced also influences outcome, and antihypertensive therapy should induce smooth and sustained blood pressure control throughout the 24-h dosing interval. Ambulatory blood pressure recording techniques, in particular, have allowed the quantitative measurement of parameters such as the short-term variability of blood pressure, which correlates significantly with cardiovascular damage in patients with hypertension. The smoothness index has been developed as an index of the homogeneity of the blood pressure reduction obtained over the 24 hours by any given treatment during a long-term trial in patients with hypertension. This parameter is more predictive of a favourable effect of antihypertensive therapy (regression of left ventricular hypertrophy) during antihypertensive therapy than the widely used trough:peak ratio. The smoothness index is a useful new tool for comparing the quality of blood pressure lowering with different antihypertensive agents. For example, candesartan cilexetil, a potent and long-acting AT1-receptor blocker, increased the smoothness index by a significantly greater extent than the prototype AT1-receptor blocker, losartan, implying a more smooth and sustained antihypertensive effect.
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PMID:Importance of smooth and sustained blood pressure control in preventing cardiovascular morbidity and mortality. 1168 74

Myocardial hypertrophy is an adaptational response of the heart to increased work load, but it is also associated with a high risk of cardiac mortality due to its established role in the development of cardiac failure, one of the leading causes of death in developed countries. Multiple growth factors and various downstream signaling pathways involving, for example, ras, gp-130 (ref. 4), JNK/p38 (refs. 5,6) and calcineurin/NFAT/CaM-kinase have been implicated in the hypertrophic response. However, there is evidence that the initial phase in the development of myocardial hypertrophy involves the formation of cardiac para- and/or autocrine factors like endothelin-1, norepinephrine or angiotensin II (refs. 7,8), the receptors of which are coupled to G-proteins of the Gq/11-, G12/13- and Gi/o-families. Cardiomyocyte-specific transgenic overexpression of alpha1-adrenergic or angiotensin (AT1)-receptors as well as of the Gq alpha-subunit, Galphaq, results in myocardial hypertrophy. These data demonstrate that chronic activation of the Gq/G11-family is sufficient to induce myocardial hypertrophy. In order to test whether Gq/G11 mediate the physiological hypertrophy response to pressure overload, we generated a mouse line lacking both Galphaq and Galpha11 in cardiomyocytes. These mice showed no detectable ventricular hypertrophy in response to pressure-overload induced by aortic constriction. The complete lack of a hypertrophic response proves that the Gq/G11-mediated pathway is essential for cardiac hypertrophy induced by pressure overload and makes this signaling process an interesting target for interventions to prevent myocardial hypertrophy.
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PMID:Absence of pressure overload induced myocardial hypertrophy after conditional inactivation of Galphaq/Galpha11 in cardiomyocytes. 1168 89


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