Search

The purpose of this study was to examine the effects of the angiotensin-converting enzyme (ACE) inhibitor cilazapril on the elastic properties of the aorta. A standard diuretic antihypertensive drug, hydrochlorothiazide, served for comparisons. Increased aortic stiffness leads to a reduction of the buffering windkessel function and is a major component in the pathophysiology of systolic hypertension, inducing an increase in left ventricular afterload and arterial pulsatile stress as well as a decrease in the subendocardial blood supply. Stiffness of arteries increases with age and blood pressure, and depends on the functional elastic structures of the aortic wall. ACE inhibitors have been shown to directly influence elastic properties of peripheral arteries. Seventeen patients with mild to moderate essential hypertension (age 45-67 years) were treated for 3 months double-blind randomized with either cilazapril (C) 5 mg daily (n = 9) or hydrochlorothiazide (HCTZ) 25 mg daily (n = 8). Aortic elastic properties were noninvasively assessed by measurement of pulse wave velocity along the aorta at rest and during isometric handgrip stress. Accelerated pulse wave velocity indicates elevated arterial stiffness and vice versa. A pressure standardized index of aortic cross-sectional distensibility (2 m) was calculated from arterial mean pressure and pulse wave velocity. Compared with pretreatment values, both therapies significantly reduced blood pressure and pulse wave velocity at rest (C: 9.4 +/- 0.9 vs. 7.7 +/- 0.7 m/sec; HcTZ: 8.9 +/- 0.3 vs. 7.8 +/- 0.4 m/sec; means +/- SEM p0.05). During isometric stress only C showed a significant decrease in pulse wave velocity (C: 11.3 +/- 0.8 vs. 9.1 +/- 0.8 m/sec; HCTZ: 9.9 +/- 0.5 vs. 9.0 +/- 0.5 m/sec; means +/- SEM p0.05). The index 2m at rest and during handgrip increased significantly (p0.05) after C but not after HCTZ. With cilazapril we obtained steeper slopes for the treatment-induced reductions in blood pressure and pulse wave velocity for both rest and handgrip stress values. Correlation of the data at rest and during stress revealed a direct relationship between blood pressure and pulse wave velocity. HCTZ linearly extended the relation observed before treatment toward lower values of blood pressure and corresponding pulse wave velocity without changing the relation per se. Cilazapril, in contrast, moved the relation between these variables and decelerated the pulse wave velocities to a greater extent than would have been expected from the corresponding blood pressure reduction (delta approximately 1 m/sec). These results in patients with mild to moderate essential hypertension support the idea that ACE inhibitors, in addition to reducing blood pressure, may exert an additional hemodynamic effect in improving the elastic properties of the aorta.

The correlation analysis of the relationship between blood lead levels and lead-in-air concentrations measured in three winter periods showed a highly significant association despite a generally loose dependence of the variables. The regression equations clearly show that there would be a finite residual blood lead value even with completely lead-free air. In the case of the populations exposed to motor traffic in this study, this residual blood lead value is 80--90% of the initial value prior to the decrease in immission. The regression equations, statistically yield results which compare convincingly with ones obtained from model calculations based on studies of metabolism and respiratory physiology. The correlation between the observed changes in blood lead and the initial absolute values of blood lead concentration demonstrates with high statistical certainty that the higher the initial level, the greater was the observed change. This type of association also implies that there is a lower limit value of blood lead below which the decrease in blood lead changes to an increase despite reduction of lead-in-air.

Inhibition of protein synthesis by cycloheximide 10(-3)M reduced the incorporation of [35S]sulphate into heparan sulphate to about 5% of untreated hepatocytes. Addition of rho-nitrophenyl beta-D-xyloside could partially revert this inhibitory effect. The sulphated material isolated from the cell layer or secretions of hepatocytes grown in presence of cycloheximide and rho-nitrophenyl beta-D-xyloside were shown to be mostly free heparan sulphate chains not bound to core protein. Covalent association of beta-xylosides to the heparan sulphates was demonstrated for heparan sulphate synthetized in the presence of [35S]sulphate, cycloheximide and the fluorogenic 4-methylumbelliferyl beta-D-xyloside. Beta-Xylosides served as an initiator of heparan sulphate chain synthesis in rat hepatocytes only in the absence of protein synthesis. Heparan sulphates primed on artificial beta-xylosides are slightly smaller in molecular size and are more sulphated than chains linked to core protein.

The tubular and tubulointerstitial renal functions of 237 patients with chronic glomerulonephritis and functional compensation corresponding to their plasma creatinine levels were investigated and the results were compared with the light microscopic findings obtained by examination of kidney interstices obtained by biopsy. Pronounced structural interstitial lesions (TiC) were found in 30% of the cases. Investigation of the predictive values of tubular function data in respect of the presence or exclusion of TiC showed that, although individual parameters of the renal function permit the exclusion of TiC disturbances with a high degree of certainty, the diagnostic value can be enhanced by considering pairs of such parameters. Five parameter combinations were found to have the highest predictive value regarding the diagnosis of TiC. These were disturbed concentration capacity accompanied by reduced ammonia excretion or total acid excretion, reduced water diuresis accompanied by disturbed ammonia excretion or total acid elimination; and, finally, the total acid excretion and maximum dilution capacity. The highest predictive values for the exclusion of TiC are shown by inconspicuous concentration capacity accompanied by normal ammonia excretion, total acid excretion, water diuresis, free water clearance or urine dilution capacity.