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

Losartan represent a novel approach in the treatment of hypertension. Clinical trials have reported a very low incidence of side effects. We describe two patients who developed increases in alanine/aspartate amino transferase of 8 and 15 times the upper normal limit, as well as thoracic pain, after a short time of treatment with losartan. The increase resolved after discontinuing losartan treatment.
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PMID:Marked hepatotoxicity associated with losartan treatment. 879 Sep 30

Losartan is an orally active angiotensin II antangonist that selectively blocks effects mediated by the stimulation of the AT1 subtype of the angiotensin II receptor. This agent, at doses of 50-150mg/day, is as effective at lowering blood pressure as chronic angiotensin converting enzyme (ACE) inhibitors. Losartan is generally well tolerated and has an incidence of adverse effects very similar, in double-blind controlled trials, to that of placebo. It does not cause coughing, the most common side-effect of the ACE inhibitors, most probably because angiotensin II antagonism has no impact on ACE, an enzyme known to process bradykinin and other cough-inducing peptides. Losartan is a promising antihypertensive agent with the potential to become a first-line option for the treatment of patients with high blood pressure.
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PMID:Angiotensin II antagonists: a new class of antihypertensive agent. 879 3

Losartan, the first specific and orally available angiotensin II receptor antagonist, is a potent antihypertensive drug with a low incidence of side effects in humans. However, the effects of losartan on insulin sensitivity and glucose metabolism have not been investigated in detail. Therefore, we carried out a randomized, double-blind study to compare the effects of losartan (50 mg QD) and metoprolol (95 mg QD) on insulin sensitivity, insulin secretion, glucose tolerance, and lipids and lipoproteins in 20 hyperinsulinemic subjects with essential hypertension. The fall in blood pressure was greater with losartan than with metoprolol. Insulin sensitivity evaluated by the euglycemic clamp technique did not change in either group after 12 weeks of treatment. Similarly, glucose oxidation (losartan: 17.0 +/- 0.9 versus 16.9 +/- 1.0 mumol/kg per minute [before versus after, P = NS]; metoprolol: 17.9 +/- 1.3 versus 16.8 +/- 1.6 [P = NS]) and nonoxidation (losartan: 22.3 +/- 4.0 versus 23.5 +/- 3.4 mumol/kg per minute [P = NS]; metoprolol: 23.3 +/- 3.2 versus 25.6 +/- 4.7 [P = NS]) remained unchanged during the last 30 minutes of the 3-hour euglycemic clamp. Losartan and metoprolol did not have any significant adverse effects on insulin secretion, glucose tolerance, or lipids and lipoproteins. In conclusion, losartan is metabolically neutral, without any significant adverse effect on glucose and lipid metabolism.
Hypertension 1996 Sep
PMID:Effects of losartan on insulin sensitivity in hypertensive subjects. 879 22

In previous studies in stroke-prone spontaneously hypertensive rats (SHRSP), we demonstrated that early-onset, long-term angiotensin-converting enzyme inhibitor treatment improved cardiac function and metabolism and increased aortic cGMP content even at sub-antihypertensive doses. These effects could be prevented by bradykinin type 2 (B2) receptor blockade with icatibant. In the present study, we studied the effects of long-term oral treatment with the angiotensin type 1 (AT1) receptor antagonist losartan (30 mg/kg per day) on functional and biochemical parameters of the heart and on cGMP content in the aorta in SHRSP treated prenatally and subsequently up to the age of 20 weeks. Losartan prevented the development of hypertension and left ventricular hypertrophy. Cardiac function measured ex vivo in isolated perfused hearts was improved, as demonstrated by significant increases in left ventricular pressure (22.4%), differentiated left ventricular pressure (dP/dtmax) (35.1%), and coronary flow (38%). The release of the intracellular enzymes lactate dehydrogenase and creatine kinase and of lactate into the coronary effluent was reduced by 46.4%, 47.2%, and 63.6%, respectively. In myocardial tissue, the concentrations of glycogen and the energy-rich phosphates ATP and creatine phosphate were increased by 43.2%, 33.1%, and 42.4%, respectively, whereas lactate was decreased by 57.0%. The aortic tissue content of cGMP was increased fivefold. Our results demonstrate that chronic blockade of AT1 receptors with losartan improved cardiac function and metabolism and increased aortic cGMP content in SHRSP to an extent similar to that observed previously after long-term angiotensin-converting enzyme inhibitor treatment at a comparably antihypertensive dose. Prevention of hypertension and cardiac hypertrophy as well as stimulation of non-AT1 receptors are discussed to explain the cardiac and vascular actions of losartan.
Hypertension 1996 Sep
PMID:Cardiac and vascular effects of long-term losartan treatment in stroke-prone spontaneously hypertensive rats. 879 23

Chronic low-dose angiotensin II (Ang II) infusion for 13 days mimics two-kidney, one clip Goldblatt hypertension and increase intrarenal Ang II levels. We performed studies to determine the time course for the enhancement of intrarenal Ang II levels and whether the increased intrarenal Ang II is a tissue-specific event and requires a receptor-mediated step. Male Sprague-Dawley rats were uninephrectomized, and either vehicle or Ang II (40 ng/min) was infused via a subcutaneous osmotic minipump. Plasma and renal Ang II levels were measured 3, 7, 10, and 13 days after minipump implantation. Compared with controls (126 +/- 2 mm Hg), systolic pressure in Ang II-infused rats exhibited a detectable increase by day 6 (146 +/- 2 mm Hg) and continued to increase to 189 +/- 5 mm Hg by day 12. Plasma Ang II levels were elevated by day 3, whereas intrarenal Ang II levels were not significantly elevated until 10 days of Ang II infusion. Renal injury characterized by focal and segmental glomerulosclerosis was evident after 13 days of Ang II infusion. Losartan (30 mg/kg per day) prevented the development of hypertension in the Ang II-infused rats for the duration of the infusion period (125 +/- 1 mm Hg) and reduced the degree of glomerular injury. Plasma renin activity was suppressed in the Ang II-infused group but was elevated markedly in both losartan-treated groups. Plasma Ang II levels were elevated in the Ang II-infused rats and were even higher during losartan treatment. Intrarenal Ang II levels were enhanced significantly (354 +/- 60 versus 164 +/- 23 fmol/g) in the Ang II-infused rats. However, losartan treatment prevented the augmentation of intrarenal Ang II caused by Ang II infusion. Heart and adrenal Ang II levels were not significantly increased in the Ang II-infused rats but were significantly elevated during losartan treatment. These results suggest that the tissue-specific elevations of intrarenal Ang II levels caused by chronic Ang II infusion are mediated by angiotensin type 1 receptor activation, which leads to either receptor-mediated internalization of Ang II, enhancement of intrarenal Ang II formation, or both.
Hypertension 1996 Oct
PMID:Receptor-mediated intrarenal angiotensin II augmentation in angiotensin II-infused rats. 884 96

Spectral analysis was recently chosen to characterize the fast oscillations, depending on the autonomic nervous system, in heart rate and blood pressure variabilities. Humoral stimuli could impinge on the low-frequency domain of blood pressure variability since the time lag to humoral system activation is greater. This study was designed to analyse low-frequency components of short-term variability of blood pressure of conscious rats in conditions where humoral systems were activated. We studied rats with two-kidney, one-clip Goldblatt hypertension in which the blood pressure level was dependent upon the renin-angiotensin and kallikrein-kinin systems. Spectral powers of the systolic and diastolic blood pressure and heart rate were computed in the high (respiratory)-, mid (0.2-0.6 Hz)- and low (0.02-0.2 Hz)-frequency bands, as detected by the fast Fourier transform technique in consecutive 102-s stationary periods. Hypertensive rats exhibited a marked low-frequency component of systolic (+261%) and diastolic (+169%) blood pressure variabilities when compared to sham-operated animals. First, losartan, a selective non-peptide angiotensin AT1 receptor antagonist, reduced this low-frequency component (-44% and -25% for systolic and diastolic blood pressure). In a second series of hypertensive rats, HOE 140, D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin, a bradykinin B2 receptor antagonist, decreased the low-frequency component of systolic (-28%) and diastolic (-40%) blood pressure. Losartan, added after HOE 140, induced a supplementary decrease of the low-frequency component (-60% and -42% for systolic and diastolic blood pressure). After the combined blockade, the low-frequency components of systolic and diastolic blood pressure variabilities of the hypertensive rats were equivalent to those of the control rats. Two-kidney, one-clip hypertension was also associated with an elevation of the mid-frequency component of the systolic blood pressure (+55%). The administration of HOE 140 did not change this component while losartan, alone or added after HOE 140, led to an increase (around +100%) in mid-frequency oscillations of systolic blood pressure. The high-frequency oscillations of systolic blood pressure were increased by losartan in the two series of hypertensive rats. Losartan increased the mid-frequency component of heart rate variability in sham-operated rats while the heart rate variability was not modified during any of the treatment periods in two-kidney, one-clip rats. In conclusion, an increase in the low-frequency component of blood pressure variability was observed in a model of hypertension where the blood pressure is dependent upon humoral activities. The reduction of the slow fluctuations following the combined blockade of the kallikrein-kinin and the renin-angiotensin systems suggested the contribution of these humoral systems to this low-frequency component of blood pressure variability.
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PMID:Contribution of the renin-angiotensin and kallikrein-kinin systems to short-term variability of blood pressure in two-kidney, one-clip hypertensive rats. 885 Nov 67

The antihypertensive activity and safety of losartan, a specific and selective antagonist of angiotensin II (subtype 1) receptors, was evaluated in 100 inpatients with mild to moderate essential hypertension. After a 2-week, single-blind, out patient placebo lead-in period, the last 2 days of which included inpatient monitoring of baseline blood pressure, the patients were assigned randomly to receive once-daily doses of either placebo; 50, 100, or 150 mg losartan; or 10 mg enalapril. Patients were treated double blind for 5 days, followed by a day for the study of drug withdrawal. Beginning with the first dose, the three doses of losartan and enalapril significantly decreased peak and trough systolic and diastolic blood pressures compared with placebo (p < or = 0.05). The area under the blood pressure curve was analyzed as an assessment of total blood pressure change throughout the day. On day 1, total blood pressure reduction with losartan (50-150 mg) was slightly less than with enalapril. By day 5 of double-blind treatment, the reduction in blood pressure in these groups was similar, suggesting that losartan has a slower onset of action than enalapril. No rebound hypertension was observed after study-drug discontinuation. Losartan was well tolerated in this trial, with an adverse event profile similar to placebo and enalapril.
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PMID:An inpatient trial of the safety and efficacy of losartan compared with placebo and enalapril in patients with essential hypertension. 887 74

Despite the availability of safe and efficacious antihypertensive agents, hypertension continues to be a major source of morbidity and mortality in the United States. Losartan, the first of a new class of agents, the angiotensin II receptor antagonists, can be administered as monotherapy in the treatment of hypertension or to complement existing therapy. The angiotensin II receptor antagonists block the effects of angiotensin II through preferential binding to angiotensin II receptor subtype AT1 on the cell membrane. Compared with angiotensin-converting enzyme inhibitors, they may provide more complete blockade of the renin-angiotensin system and be associated with a lower frequency of cough as a side effect.
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PMID:A new class of antihypertensive therapy: angiotensin II receptor antagonists. 888 79

The discovery of orally active nonpeptide angiotensin II (A II)-receptor antagonists has initiated a growing understanding of the physiologic and pathophysiologic roles of A II. Losartan is the first of the new class of antagonists that block all the well-known effects of A II, including vasoconstriction, aldosterone release, renin release (negative feedback), and the stimulation of thirst. A II-receptor subtypes have been described, with losartan antagonism defining the AT1 subtype and with PD123319 antagonism defining the AT2 subtype. The AT1 receptor is G-protein-coupled, involving PLC, PLA2, PLD, or adenylate cyclase and the release of intracellular calcium. The receptor-response coupling of the AT2 site remains elusive but may involve protein tyrosine phosphatase and subserve an antiproliferative role. Losartan as the prototype of an AT1-selective antagonist: i) inhibits A II binding, ii) antagonizes effects of A II in vivo and in vitro, and iii) lowers blood pressure in models of A II-dependent hypertension A II stimulates growth in vitro (DNA and protein synthesis) and in vivo (cardiac and vascular hypertrophy), and these effects are blocked by losartan. Losartan, like angiotensin-converting enzyme inhibitors, has significant renal, cardiac, and cerebral protective effects in models of renal failure, cardiac failure, and stroke, confirming the pathologic role of A II in these models. The pioneering studies in experimental animals are being confirmed by a growing number of other AT1-selective blockers and provide the basis of use of losartan for hypertension and its clinical trial in other disease states.
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PMID:The diversified pharmacology of angiotensin II-receptor blockade. 891 41

Losartan is the first drug of a new therapeutic class, the angiotensin II (A II)-receptor antagonists, to be clinically studied and become available for the management of hypertension. Clinical experience with losartan from worldwide, double-blind, controlled studies has been obtained in more than 2900 hypertensive patients treated with losartan alone or in combination with hydrochlorothiazide, with 1700 patients receiving treatment for more than a year. The efficacy of losartan was evaluated in the young and old, in different degrees of hypertension, in blacks and nonblacks, and in patients with renal impairment. Tolerability parameters were assessed by subgroup as well. In dose-ranging studies, 50 mg once daily has generally been shown to produce near maximum effects and a dose of 100 mg does not produce additional effects. The efficacy of losartan (50 to 100 mg once daily) has been compared to atenolol (50 to 100 mg once daily), felodipine ER (5 to 10 mg once daily), and enalapril (20 mg once daily). The blood pressure-lowering effect of losartan was comparable to felodipine, enalapril, and atenolol. The efficacy of losartan was demonstrated using ambulatory blood pressure monitoring, which showed that losartan 50 mg once daily produced gradual reduction in blood pressure, providing 24-h control without affecting the body's circadian rhythm. In subgroups of study populations, no differences in efficacy were noted with respect to age, gender and the severity of hypertension. No initial dosage adjustment is necessary in the elderly and patients with renal impairment (even those on dialysis). Among blacks, the mean response of losartan was lower, which is not surprising given the lesser activation of the renin-angiotensin system in this population. A subgroup safety and tolerability analysis confirmed that there were no important differences in adverse events when assessed by age, race, or gender. The data obtained from controlled clinical trials conducted with losartan, the first A II-receptor antagonist, has shown that a single daily 50-mg dose provides adequate 24-h control of blood pressure in most patients with comparable efficacy to other classes and is well tolerated.
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PMID:Global efficacy and tolerability of losartan, an angiotensin II subtype 1-receptor antagonist, in the treatment of hypertension. 891 46


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