Angiotensin-converting enzyme gene insertion/deletion polymorphism and left ventricular hypertrophy in hemodialysis patients.

The relationships between angiotensin-converting enzyme (ACE) gene insertion (I) / deletion (D) polymorphism and left ventricular hypertrophy induced by hypertension or idiopathic hypertrophic cardiomyopathy have been studied. However, little is known about the association between this polymorphism and left ventricular hypertrophy induced by volume overload. The relationship between left ventricular hypertrophy and the ACE gene I/D polymorphism was examined in 80 maintenance hemodialysis patients (mean age: 60.1+/-1.4 years). Multivariate regression analysis showed that the left ventricular mass index calculated by M-mode echocardiography was associated with serum creatinine (p = 0.040), male gender (p = 0.027), antihypertensive drug treatment (p = 0.026), weight gain between hemodialysis (p = 0.018) and mean blood pressure after hemodialysis (p=0.010), but not with ACE I/D genotype (p = 0.69). These findings suggest that although hemodialysis patients seem to be under volume overload, ACE genotype may not be involved in their left ventricular hypertrophy. Hypertension and other factors related to renal failure are involved in the left ventricular hypertrophy in chronic hemodialysis patients.

Augmented sympathetic nerve activity in response to stressors in young borderline hypertensive men.

To determine whether there may be an abnormality in sympathetic nerve activity in response to physical and psychological stressors, we microneurologically recorded muscle sympathetic nerve activity in 11 normotensive and 9 borderline hypertensive, age-matched men. Supine blood pressure, plasma levels of epinephrine and norepinephrine and muscle sympathetic nerve activity were measured before and during a cold pressor test or a mental arithmetic test. The resting basal values of muscle sympathetic nerve activity, blood pressure and plasma epinephrine were significantly higher in the borderline hypertensives than in the normotensives (P less than 0.05). Plasma norepinephrine levels tended to be higher in the borderline hypertensives than in the normotensives but not to a significant extent (P less than 0.10). The cold test produced significantly exaggerated pressor and muscle sympathetic nerve responses (P less than 0.05) with a trend towards an increase in plasma norepinephrine (P less than 0.10) in the borderline hypertensives as compared with normotensives. The mental arithmetic test produced significantly enhanced pressor and plasma epinephrine responses in the borderline hypertensives as compared with the normotensives (P less than 0.05). During the mental arithmetic test the muscle sympathetic nerve activity decreased significantly in the normotensives (P less than 0.05) but not in the borderline hypertensives. These findings indicate that in people with borderline hypertension an abnormality exists in sympathetic nerve activity at rest and in response to stressors.

Renal haemodynamics and comparative effects of captopril in patients with benign- or malignant-essential hypertension, or with chronic renal failure.

Effects of captopril on arterial pressure (AP) and renal function were investigated in patients with non-malignant "benign" or malignant phase essential hypertension (EH group), or with chronic renal failure (CRF group). After captopril administration, AP and renal vascular resistance (RVR) decreased significantly, and renal blood flow (RBF) and plasma renin activity (PRA) increased in both groups. Glomerular filtration rate (GFR) increased in the EH group, but was unchanged in CRF. Filtration fraction decreased in the malignant hypertension and CRF groups. Significant correlations were found between baseline PRA and baseline RVR, and the captopril-induced decrease in mean AP, decrease in RVR, increase in RBF, and increase in GFR in the EH group, while these associations were not observed in CRF. These results indicate that the high AP, RVR, suppressed RBF and GFR in the EH group were closely related to activity of the renin-angiotensin system, but not so the low RBF and GFR in CRF. Small doses of captopril may improve impaired renal function in EH, and may not cause deterioration in the CRF group.

Serum concentration and effects of a single dose of enalapril maleate in patients with essential hypertension.

The antihypertensive effect of a non-sulfhydryl, long acting ACE (angiotensin converting enzyme) inhibitor, MK-421, was evaluated by administering a single dose of 10 mg to 13 patients with mild to moderate essential hypertension. The pharmacokinetic profile of MK-421 and its potent active metabolite, MK-422, was also assessed, together with the effect on the various components of the renin-angiotensin system. A single dose of MK-421 produced a significant fall in MBP from 2 to 24 hours post-drug. As could be expected, plasma ACE activity was suppressed up to 24 hours after MK-421. The half-life of MK-422, Cmax and [AUC]24(0) of MK-421 and MK-422 were measured. No significant change in plasma bradykinin or urinary excretion rate of kallikrein was observed, whereas a slight increase was observed in the urinary excretion rate of kinins after MK-421 in 8 patients. Significant correlations were observed between pretreatment PRA levels and the maximum fall in MBP.

Renal haemodynamics and the renin-angiotensin system in adolescents genetically predisposed to essential hypertension.

Relationships between renal haemodynamics and the renin-angiotensin system were examined in 128 male adolescents with differing predispositions to hypertension. Baseline renal vascular resistance (RVR) was significantly elevated in the normotensive subjects with a positive family history, NT (FH+) group, than in the normotensives with a negative family history, NT (FH-) group, while there were no significant differences in other characteristics between the two groups. The borderline hypertensive subjects with a positive family history, BH (FH+) group, showed an even bigger increase in RVR and also had elevated plasma renin activity (PRA). In the NT (FH+) and BH (FH+) groups RVR correlated significantly with PRA levels. When captopril was given, the increased RVR in the NT (FH+) and BH (FH+) groups decreased, in correlation with baseline PRA, to levels not significantly different from those in the NT (FH-) group, in which no significant changes occurred in RVR. These results suggest that RVR may increase primarily in adolescents genetically predisposed to essential hypertension and that the renin-angiotensin system may play an important role in the mechanism of this increase in RVR.

Simple portable device for sampling a whole day's urine and its application to hypertensive outpatients.

To simplify 24-hour urine collection for epidemiological and clinical examinations, we devised a portable, semiautomatic urine sampling cup with divided partitions. The cup, 6.6 cm in diameter and 14 cm in height, is double-bottomed and has a pipe-shaped scale and a cock leading to the lower compartment. It is so devised that 1/m of the urine volume excreted into the upper compartment each time remains in the pipe scale, and then comes down into the lower compartment by manipulating the cock. The urine in the lower compartment remains when the urine in the upper compartment is discarded. The cup is carried in a vinyl bag. By repeating this manipulation. 1/m of the total urine excreted during 24 hours can be collected in the small cup (proportional sampling method). When the 24-hour urinary sodium excretion measured by the conventional method and that measured by this method were compared, the correlation coefficient (r) was 0.98, and the average variation was 2.0 +/- 10.8 (SD) mEq (n = 32). Use of this device for outpatients was convenient and enabled counseling on salt intake.

[Clinical application of extracellular fluid measurement using 35S-sodium sulfate (author's transl)].

ECF (extracellular fluid volume) was measured by 35S-sodium sulfate and the same time value of PV (plasma volume) was determined by 131I-RISA in each subject. In normal ECF was an average of 181 ml/kg, 6.21 l/m2 and PV was 49.1 ml/kg, 1.69 l/m2. Both values of ECF and PV in essential hypertension were almost the same as those in normal. In congestive heart failure ECF was 232 ml/kg, 7.51 l/m2 and PV was 55.8 ml/kg, 1.80 l/m2. In the patients with ascites or edema, ECF was 256 ml/kg, 8.69 l/m2 and PV was 53.0 ml/kg, 1.79 l/m2. The results of the measurement by the two compounds also corresponded to the conditions of the patients who showed electrolytes disorders (ACTH deficiency, SIADH) and was improved by treatment.