Hypotension in patients with coronary disease: can profound hypotensive events cause myocardial ischaemic events? (1/36)

OBJECTIVE: To determine whether anginal episodes might be related to extremes of hypotension in patients with ischaemic heart disease taking drugs to treat angina and heart failure. DESIGN AND SETTING: Observational study of patients with ischaemic heart disease attending an urban tertiary referral cardiology centre. INTERVENTIONS AND OUTCOME MEASURES: A selected patient population was enrolled, having: angina on one or more hypotensive cardiovascular medications; hypotension on clinic or ambulatory measurement; and a resting ECG suitable for ambulatory monitoring. Patients had echocardiography, ambulatory blood pressure monitoring, and Holter monitoring. Hypotension induced ischaemic (HII) events were defined as episodes of ST segment ischaemia occurring at least one minute after an ambulatory blood pressure measurement (systolic/diastolic) below 100/65 mm Hg during the day, or 90/50 mm Hg at night. RESULTS: 25 suitable patients were enrolled, and 107 hypotensive events were documented. 40 ST events occurred in 14 patients, of which a quarter were symptomatic. Fourteen HII events occurred in eight patients, with 13 of the 14 preceded by a fall in diastolic pressure (median diastolic pressure 57.5 mm Hg, interquartile range 11, maximum 72 mm Hg, minimum 45 mm Hg), and six preceded by a fall in systolic pressure (chi(2) = 11.9, p < 0.001). ST events were significantly associated with preceding hypotensive events (chi(2) = 40.2, p < 0.0001). Patients with HII events were more frequently taking multiple hypotensive drug regimens (8/8 v 9/17, chi(2) = 5.54, p = 0.022). CONCLUSIONS: In patients with ischaemic heart disease and hypotension, symptomatic and silent ischaemia occurred in a temporally causal relation with hypotension, particularly for diastolic pressures, suggesting that patients with coronary disease may be susceptible to ischaemic events incurred as a result of low blood pressure caused by excessive hypotensive drug treatment.  (+info)

Local pulse pressure and regression of arterial wall hypertrophy during long-term antihypertensive treatment. (2/36)

BACKGROUND: Local pulse pressure (PP) is an independent determinant of carotid artery wall thickness, stronger than mean blood pressure (BP). The present study was designed to assess whether a beta-adrenoceptor antagonist-based or an ACE inhibitor-based treatment was able to reduce carotid artery wall hypertrophy through a reduction in carotid PP rather than by lowering mean BP and whether the influence of local PP reduction could also be detected at the site of a muscular artery, the radial artery. METHODS AND RESULTS: Ninety-eight essential hypertensive patients were randomized to 9 months of double-blind treatment with either celiprolol or enalapril. Arterial parameters were determined with high-resolution echo-tracking systems. PP was measured locally with applanation tonometry and independently of mean BP. After 9 months of treatment, mean BP, carotid PP, and intimal-medial thickness (IMT) decreased significantly, with no difference between the 2 groups. The reduction in carotid PP but not in mean BP was a major independent determinant of the reduction in carotid IMT. Radial artery IMT and PP decreased significantly with both treatments. However, the reduction in radial artery IMT was not related to the changes in radial artery PP. CONCLUSIONS: The regression of carotid artery wall hypertrophy during long-term antihypertensive treatment was dependent on the reduction in local PP rather than on the lowering of mean BP. The effect of PP lowering on IMT reduction was observed at the site of an elastic artery but not at the site of a muscular artery.  (+info)

Effect of celiprolol on cardiac hypertrophy in hypertension. (3/36)

The present study was undertaken to clarify whether celiprolol and atenolol, beta1-selective beta blockers with and without intrinsic sympathomimetic activity (ISA), respectively, might improve ischemic damage in the isolated perfused hearts of spontaneously hypertensive rats (SHR), and whether long-term treatment with celiprolol may reduce left ventricular hypertrophy (LVH) in patients with essential hypertension. Atenolol (50 mg/kg/day) or celiprolol (300 mg/kg/day) for 7 weeks significantly reduced the blood pressure in SHR to the same degree, and both drugs decreased the heart rate, but the magnitude of the fall in heart rate was significantly higher with atenolol treatment than with celiprolol treatment. Both treatments significantly reduced the ratio of LV weight to body weight in SHR and significantly improved the coronary reserve in SHR to the same extent. Both treatments significantly improved the extent of recovery of the pressure-rate product and the extent of percent recovery of the coronary flow after reperfusion following 30 min of ischemia in SHR. Celiprolol treatment in patients with essential hypertension for 12 months significantly decreased interventricular septal thickness (IVST)+LV posterior wall thickness (PWT) and LV mass index (LVMI), but there was no significant correlation between IVST+PWT or LVMI and blood pressure before and after treatment. IVST+PWT and LVMI were significantly decreased after 3 months of treatment and these LVH indices were significantly smaller after 6 and 12 months of treatment than after 3 months of treatment. In conclusion, both celiprolol and atenolol treatment reduced LVH and improved the ischemic damage in SHR. In essential hypertensive patients with LVH, celiprolol treatment effectively reduced blood pressure and achieved LVH regression.  (+info)

Effects of vasodilatory antihypertensive agents on endothelial dysfunction in rats with ischemic acute renal failure. (4/36)

Ischemic acute renal failure is associated with vascular endothelial dysfunction. We examined whether vasodilatory antihypertensive agents would improve endothelial function in rats with ischemia/reperfusion renal injury. Rat kidneys were isolated and perfused after clipping of the bilateral renal arteries for 45 min and reperfusion for 24 h, and renal perfusion pressure and nitric oxide concentration in the venous effluent (chemiluminescence assay) were monitored. Preischemic administration of celiprolol (a beta-blocker; 100 mg/kg p.o.), benidipine (a calcium channel blocker; 1 mg/kg p.o.), or imidapril (an angiotensin converting-enzyme inhibitor; 3 mg/kg p.o.) restored endothelial function in rats subjected to acute renal ischemia (deltarenal perfusion pressure [10(-8) M acetylcholine]: sham -42+/-3%, ischemia -31+/-1%, ischemia +celiprolol -39+/-1%*, ischemia+benidipine -38+/-2%*, ischemia+imidapril -42+/-2%*; *p<0.05 vs. ischemia). Serum urea nitrogen and creatinine levels were also lower in the treated groups. Furthermore, ischemia-induced decreases in the response to acetylcholine and renal excretory function were smaller in SHR than in deoxycorticosterone-salt hypertensive rats, in which endothelial damage was marked. These results suggest that preischemic endothelial function may influence the degree of ischemic renal injury. Calcium channel blockers, converting-enzyme inhibitors, and endothelial NO synthase-activating beta-blockers had beneficial effects on renovascular endothelial dysfunction due to ischemia.  (+info)

Angiotensinogen gene M235T polymorphism and reduction in wall thickness in response to antihypertensive treatment. (5/36)

The angiotensinogen M235T polymorphism has been linked to hypertension and cardiovascular disease. Carotid intima-media thickness (IMT) is an early marker of atherosclerosis. The objectives of the present study were to determine in previously untreated essential hypertensive patients whether carotid IMT was associated with the M235T polymorphism, and to determine whether the M235T polymorphism could influence the reduction of carotid IMT by antihypertensive treatment. Common carotid artery IMT was determined with a high-definition echotracking system in 98 previously untreated hypertensive patients in a cross-sectional study. A subgroup of 56 patients was included in a randomized double-blind parallel group study comparing the effect of the angiotensin-converting-enzyme-inhibitor enalapril with that of the beta-blocker celiprolol during a 5 month period. In the cross-sectional study, a multivariate analysis showed that the M235T genotype was a significant independent determinant of carotid IMT, explaining 7% of the variance. Carotid IMT was higher in patients homozygous for the T allele than in MM patients. In the longitudinal study, the reduction in carotid IMT after antihypertensive treatment was significantly ( P <0.01) higher in patients carrying the TT genotype than in patients carrying the MM genotype, despite similar reductions in blood pressure and independently of drug type. In conclusion, these data suggest that the angiotensinogen TT genotype at position 235 is a genetic marker for early carotid atherosclerosis in a hypertensive population and its regression under antihypertensive treatment.  (+info)

Selectivity of antagonist and partial agonist activity of celiprolol in normal subjects. (6/36)

1. The aims of this study were to assess the relative beta 1/beta 2 selectivity of the antagonist and partial agonist activity (PAA) of celiprolol in man. 2. Eight normal males received single oral doses of celiprolol 200 mg (C200), 400 mg (C400) and 800 mg (C800); atenolol 50 mg (A50), 100 mg (A100) and 200 mg (A200); nadolol 40 mg (N40) and placebo (PL), administered in a single-blind, randomised crossover design. 3. At rest, in the presence of low levels of circulating adrenaline and noradrenergic tone, a low dose of celiprolol (C200) showed evidence of beta 1-PAA by significant increases in systolic blood pressure and resting heart rate. At higher doses (C400, C800), beta 2-PAA became evident by a significant increase in postural finger tremor, whereas C200 had no effect. 4. In the presence of a beta 1-adrenoceptor agonist, as assessed by reduction of exercise tachycardia, increasing doses of celiprolol produced significantly less beta 1-adrenoceptor blockade compared with atenolol. Furthermore, there was no increase in beta 1-adrenoceptor blockade beyond C400. 5. In the presence of a beta 2-adrenoceptor agonist, as assessed by blunting of terbutaline-induced chronotropic, hypokalaemic and finger tremor responses, celiprolol exhibited less beta 2-adrenoceptor blockade than comparable doses of atenolol used in clinical practice. 6. Exercise hyperkalaemia was blunted significantly by C400 and C800 in comparison with all doses of atenolol and nadolol.(ABSTRACT TRUNCATED AT 250 WORDS)  (+info)

The effect of celiprolol on glomerular filtration rate and renal blood flow in patients with chronic renal impairment and healthy volunteers. (7/36)

A double-blind, placebo controlled study investigated the effects of celiprolol, 200 mg daily for 7 days, on glomerular filtration rate (GFR) and estimated renal blood flow (ERBF) in eight healthy volunteers and eight patients with chronic renal insufficiency. In healthy volunteers the mean difference in GFR was 4.8 ml min-1 (95% CI -8.2 to 17.7 ml min-1) and the mean difference in ERBF was 49.8 ml min-1 (95% CI -47.5 to 147 ml min-1) after celiprolol. In patients with chronic renal insufficiency the mean difference in GFR was -2.1 ml min-1 (95% CI -64.6 to 65.8 ml min-1). The study had sufficient power to detect a 15% change in GFR for normals and 10% for patients, and for ERBF, changes of 14% and 23% were detectable. Celiprolol at a dose of 200 mg daily for 7 days can be used in patients with chronic renal insufficiency without adversely affecting GFR or ERBF.  (+info)

Celiprolol activates eNOS through the PI3K-Akt pathway and inhibits VCAM-1 Via NF-kappaB induced by oxidative stress. (8/36)

Vascular cell adhesion molecule-1 (VCAM-1) and reactive oxygen species play critical roles in early atherogenesis, and nitric oxide (NO) is an important regulator of the cardiovascular system. Although celiprolol, a specific beta1-antagonist with weak beta2-agonistic action, stimulates endothelial nitric oxide synthase (eNOS) production, the mechanisms remain to be determined. Because it was recently reported that phosphatidylinositol 3-kinase (PI3K) and its downstream effector Akt are implicated in the activation of eNOS and that regulation of VCAM-1 expression is mediated via nuclear factor-kappaB (NF-kappaB), we hypothesized that celiprolol activates phosphorylation of eNOS through the PI3K-Akt signaling pathway; that celiprolol modulates VCAM-1 expression, which is associated with inhibiting NF-kappaB phosphorylation; and that celiprolol suppresses NAD(P)H oxidase p22phox, p47phox, gp91phox, and nox1 expression in the left ventricle of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. eNOS and Akt phosphorylation upregulated by celiprolol alone were suppressed by treatment with celiprolol plus wortmannin. Increased expression of VCAM-1, p22phox, p47phox, gp91phox, nox1, activated p65 NF-kappaB, c-Src, p44/p42 extracellular signal-regulated kinases, and their downstream effector p90 ribosomal S6 kinase phosphorylation in DOCA rats was inhibited by celiprolol. Celiprolol administration resulted in a significant improvement in cardiovascular remodeling and suppression of transforming growth factor-beta1 gene expression. In conclusion, celiprolol suppresses VCAM-1 expression because of inhibition of oxidative stress, NF-kappaB, and signal transduction, while increasing eNOS via stimulation of the PI3K-Akt signaling pathway and improving cardiovascular remodeling.  (+info)

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