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  • 1
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Pharmacological inhibition of nitric oxide (NO) synthesis is known to produce acute and chronic hypertension in many animal species, but the underlying mechanisms mediating the hypertension are not completely understood. In particular, the pathogenetic roles of sodium sensitivity and the sympathetic nervous system in this model of hypertension are controversial. The present study was designed to test the hypothesis that long-term administration of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) to male Sprague-Dawley rats would produce a sodium-sensitive hypertension and that the enhanced activity of the sympathetic nervous system in this type of hypertension contributes to the sodium sensitivity.2. NG-Nitro-L-arginine methyl ester was added to drinking fluid for 8 weeks at a concentration of 16 mg/dL. Rats received tap water for the first 4 weeks of the study and were then divided into two groups and placed on either a normal or high sodium intake (ingestion of either tap water or 0.9% NaCl, respectively). Awake systolic blood pressure was measured by the tail-cuff method every week. Urinary excretion rates of the stable NO metabolites and catecholamines during NO synthesis inhibition were examined.3. Long-term administration of L-NAME produced a marked and sustained elevation in arterial pressure without altering urine flow, or sodium excretion rate. NG-Nitro-L-arginine methyl ester-induced hypertension was accompanied by a decreased urinary excretion of the stable NO metabolites NO2– and NO3– and was aggravated when rats drank 0.9% NaCl in place of tap water. Urinary excretion of adrenaline and noradrenaline, but not dopamine, in L-NAME-treated rats increased significantly within the first week of the study compared with control rats. L-Arginine (2 g/dL in drinking fluid) completely reversed the elevation of arterial pressure as well as the decrease in urinary NO2– and NO3– excretion and the increased urinary excretion of catecholamines associated with L-NAME treatment by 3 weeks of concomitant administration.4. These results suggest that long-term inhibition of NO synthesis produces a sodium-sensitive hypertension and that changes in sympathetic nerve activity may, at least in part, contribute to the sodium sensitivity in this type of hypertension.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Cardiovascular drug reviews 20 (2002), S. 0 
    ISSN: 1527-3466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Pioglitazone is the second thiazolidine derivative used clinically in the type 2 diabetes mellitus (DM). In the prediabetic stage, hyperinsulinemia or insulin resistance has been suggested to be closely associated with the oxidative stress. The first thiazolidine derivative used to treat DM, troglitazone, is chemically related to α-tocopherol, a known anti-oxidant. Troglitazone prevents tissue damage, but has been reported to produce hepatotoxicity. Pioglitazone strongly increases insulin sensitivity, improves glucose and lipid metabolism and showed no evidence of hepatotoxicity. The mechanism of the antidiabetic action of pioglitazone involves activation of insulin receptors and /or high affinity for peroxisome proliferator-activated receptor γ (PPARγ). Hydroxylation of the phenyl and pyridine rings in the chemical structure of pioglitazone may facilitate the scavenging of hydro-xyl radicals. The direct antioxidant effect of pioglitazone may contribute to its effect on insulin resistance. The hypoglycemic and hypolipidemic effects of pioglitazone are likely to reduce the expression of TNFα. The reduction in the oxidative stress may lead to the suppression of TGFβ and of collagen accumulation. A decrease in collagen content is likely to improve left ventricular diastolic function and distensibility of the aortic wall. Reduction in the oxidative stress may prevent the proliferation of vascular smooth muscle cells and contribute to the decrease in the aortic wall stiffness.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Cardiovascular drug reviews 20 (2002), S. 0 
    ISSN: 1527-3466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Olprinone is a newly developed phosphodiesterase III inhibitor characterized by several properties. First, olprinone has positive inotropic and vasodilator actions and improves myocardial mechanical efficiency. Second, olprinone augments cerebral blood flow by a direct vasodilatory effect on cerebral arteries. The cerebrovascular reactivity to olprinone is marked in patients with impaired cerebral circulation. Third, olprinone selectively improves carotid artery distensibility, which may be attributable to differences in the arterial structural components or the reactivity of smooth muscle cells to olprinone. Fourth, olprinone improves inadequate redistribution of brain perfusion and may prevent cerebral metabolic abnormalities in heart failure.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1615-2573
    Keywords: Phosphodiesterase III inhibitor ; Olprinone ; Vascular elasticity ; Stiffness parameter β ; Echocardiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Although the effects of phosphodiesterase III (PDE III) inhibitors as vasorelaxants have been well documented, there are only few data on the wall response of different arteries. We evaluated the arteryspecific effect of olprinone (OP), one of the PDE III inhibitors, on the major branches of human arteries and peripheral circulation. In 14 healthy subjects (average age: 57.5 ± 21.2 years), systolic and diastolic diameters (D s andD d, respectively) and the time velocity integral (VI) of flow velocity patterns were measured by M-mode and Doppler echocardiography in the carotid artery (CA), the ascending aorta (asAo), the abdominal aorta (abAo), and the left ventricular outflow tract. Blood pressure (BP) was simultaneously measured using a cuff sphygmomanometer. Measurements were taken before and 20min after a bolus injection of OP (0.2µg/kg). Distensibility (D s −D d), stiffness parameter β (ln(systolic BP/diastolic BP)/(D s/D d − 1)), cardiac output (CO: (Flow Area) × VI × HR at left ventricular outflow), selective flow volume (FV: (Flow Area) × VI × HR at CA or abAo), and vascular resistance (VR: mean BP/(CO or FV)) were then calculated. The distensibility increased significantly after OP administration (P = 0.0015), but that of the asAo or abAo did not change. Although there was a significant increase in CO (P = 0.001) and a significant decrease in systemic VR (P = 0.001) following OP administration, the FV and VR of both CA and abAo did not change significantly. The selectiveness of the effect of OP was demonstrated in terms of the CA wall distensibility. This was thought to be attributable to the differences in the structural components or the reactivity of smooth muscle cells to OP.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1615-2573
    Keywords: Key words Diastolic function ; Prognosis ; Myocardial infarction ; Color M-mode Doppler echocardiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Color M-mode Doppler echocardiography (CMD) has been utilized in assessing left ventricular (LV) filling dynamics. We tested a novel CMD index, the depth of the spatiotemporal maximum of early diastolic inflow (D-maxV) in the left ventricle, to clarify its significance in assessing LV diastolic function. In 26 normal subjects and 32 patients with ischemic heart disease, D-maxV was determined with CMD as the distance from the mitral valve opening point to the center of the aliasing area in early diastole. Transmitral flow velocity was measured with pulsed Doppler. During routine catheterization, high-fidelity LV pressure measurements yielded diastolic variables in patients. D-maxV was significantly lower in the patients than the normals (13.0 ± 7.0 vs 23.4 ± 6.8 mm, P 〈 0.0001). D-maxV exhibited significant linear correlations with the minimal first derivative of LV pressure (r = 0.72, P 〈 0.01), the time constant of isovolumic relaxation (r = −0.67, P 〈 0.01), and LV minimal pressure (r = −0.53, P 〈 0.02) in the patients with wide ranges of peak early to late inflow velocity ratio (0.43–3.9) and deceleration time of early filling (79–293 ms). D-maxV showed an inverse correlation with LV end-diastolic pressure (r = −0.53, P 〈 0.02) and no significant correlation with mean pulmonary capillary wedge pressure. Moreover, Kaplan-Meier analysis focusing on the patients with myocardial infarction revealed that the group with D-maxV 〈 10.4 mm (n = 13) exhibited a lower cumulative cardiac event-free rate than that with D-maxV ≥ 10.4 mm (n = 14) (49.4% vs 92.9% at 5 years, P 〈 0.05). The depth of the spatiotemporal maximum of early diastolic LV inflow velocity reflects LV relaxation and is free of pseudonormalization. Evaluation of the LV relaxation separately from preload may have a prognostic value for myocardial infarction.
    Type of Medium: Electronic Resource
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