Resolution of genetic and cultural inheritance in twin families by path analysis: application to HDL-cholesterol.

A path model and associated statistical method for the analysis of data on twin families are introduced and applied to high density lipoprotein cholesterol (HDL-c) observations in the Swedish Twin Family Study. The proposed path model incorporates both genetic and environmental sources of familial resemblance, maternal environmental effects, intergenerational differences in heritabilities, marital resemblance due to either primary or secondary phenotypic homogamy, and twin residual environmental correlations. Application of the model to HDL-c levels resulted in parameter estimates consistent with those reported in earlier reviews and in the analysis of nuclear family and twin data. Genetic heritability was estimated as h2 = .363 +/- .243, cultural heritability as c2 = .187 +/- .082, and the proportion of phenotypic variance due to residual environmental effects as r2 = .450 +/- .207. Although the parameter estimates were comparable, the statistical tests of hypotheses were, relative to other designs, of low statistical power. It appears that environmental indices are necessary for powerful tests of hypotheses.     

Genetic regulation of plasma and red blood cell magnesium concentrations in man. I. Univariate and bivariate path analyses.

This paper concerns an analysis of family resemblance for magnesium concentrations, based on data from nuclear families and twins. Neither red blood cell magnesium nor plasma magnesium varies with age in children (under 20 years of age). Whereas adult plasma magnesium varies linearly with age, the red cell magnesium clearly showed a nonlinear trend: quadratic for males and a fifth-degree polynomial for females. Transformed magnesium concentrations generated six correlations in nuclear families and twins for each of the two traits. Separate univariate analyses, using a simple linear model with four parameters, strongly suggested that genetic factors are primarily responsible for the observed family resemblance. Both traits were then analyzed simultaneously using a simple bivariate model. We found that one common genetic factor alone could not explain all the 24 correlations generated for the bivariate analysis. The most parsimonious model involved only three parameters: genetic heritability for red blood cell magnesium (.922 +/- .014), genetic heritability for plasma magnesium (.721 +/- .040), and the genetic correlation between the two traits (.233 +/- .040).     

The transmission of schizophrenia under a multifactorial threshold model.

Family studies of schizophrenia have reported elevated rates of both definite and definite-plus-probable schizophrenia among the relatives of definite schizophrenics. These elevated rates imply a strong association between the two forms of diagnosis and suggest some form of familial transmission. Here we have used recently developed maximum likelihood methods to investigate this association and characterize the nature of the familial transmission. Results indicated that although the two forms of diagnosis were strongly related, they could not be considered alternative manifestations of a single liability distribution. Heritability estimates for either form of diagnosis were comparable (h2 = .668 +/- .052 and c2 = .191 +/- .038 for definite while h2 = .628 +/- .073 and c2 = .236 +/- .106 for definite-plus-probable), although cultural transmission (i.e., c2) was statistically significant only for definite-plus-probable. For either form of diagnosis, residual twin resemblance was statistically significant and could not be explained in terms of the effects of genetic dominance. These results are comparable to those of an earlier analysis based upon a similar data set. Finally, the statistical correction used to adjust for between-study heterogeneity in morbidity risk figures did not noticeably alter the parameter estimates.     

Family resemblance for glucose tolerance in a Melanesian population, the Tolai

Path analysis of family resemblance for plasma glucose concentration, 2 h after an oral glucose challenge, failed to detect significant genetic heritability. There were no intergenerational differences and marital resemblance was moderate. Over one-third of sibling environmental similarity was due to non-inherited factors. Cultural inheritance was very strong, tending to mimic genetic inheritance, and cultural heritability was considerable. Measures of obesity were included in the environmental index, an estimate of familial environment, in this analysis, for comparability with previous studies. Since obesity appears, in part, to be a heritable trait, in future studies a bivariate approach to family resemblance for both glucose tolerance and obesity could yield important additional insight.     

Beta-adrenoceptor and adenylate cyclase function in the infarct model of rat heart failure.

In order to determine the possible etiology for diminished inotropic responsiveness to catecholamines in the infarction model of chronic congestive heart failure in rats, we studied beta-adrenoceptor number and site-specific stimulated adenylate cyclase activity in noninfarcted left ventricular tissue of rats at 3 months after ligation of the left coronary artery. Rats were divided into sham, small infarct, and large infarct groups according to infarct size. The large infarct groups showed increased right ventricle to body weight ratio (0.93 +/- 0.07 mg/g for the large infarcts vs 0.52 +/- 0.02 and 0.54 +/- 0.02 mg/g for the shams and small infarcts, respectively). Beta-Adrenoceptor number among the groups was similar (shams, 27 +/- 1 fmol/mg; small infarcts, 26 +/- 1 fmol/mg; and large infarcts, 29 +/- 1 fmol/mg), as was Kd (20 +/- 1 pmol, 18 +/- 2 pmol, and 18 +/- 2 pmol, respectively). Site-specific stimulation of adenylate cyclase using isoproterenol, Gpp(NH)p, forskolin, and MnCl2 revealed no significant differences among the groups. We conclude that this system is not responsible for the altered inotropic responsiveness to catecholamines seen in this model.     

Facial resemblance of Japanese children to their parents

Facial resemblance between parents and their children could be an indicator of genetic relationship, and selective pressure could bias the resemblance of appearance. We assessed the degree of resemblance of 38 Japanese children (3–6 years old) to each of their parents using photographs. We asked nonrelatives to assess which of the parents each child resembled, manipulating indications of the sex of the children. Variance in the degree of resemblance between the children and their fathers was very large. Although the basic facial appearance of each parent can be reflected in each child with 50% probability, the children did not equally show the facial characteristics of each parent at the individual level. The indication of sex had no significant effect on the assessment of resemblance. On the other hand, a questionnaire given to the assessors revealed that, as children, they tended to be said to resemble the opposite-sex parent. This result indicates that alleged resemblance does not reflect an actual condition but rather might have cultural meaning. Electronic Publication     

The Cincinnati Lipid Research Clinic family study: cultural and biological determinants of lipids and lipoprotein concentrations.

A general linear model is described here for cultural and biological inheritance of lipids and lipoproteins. This model involves 10 parameters to be estimated from a total of 17 correlations, leaving ample degrees of freedom to test the goodness of fit. The model fits very well to each of the five lipid and lipoprotein variables analyzed here from a Lipid Research Clinic family data set. Both genetic and cultural inheritance are significant for each trait with the single exception that triglyceride levels fail to support genetic inheritance. Under the most parsimonious hypothesis, the genetic heritability (h2) ranges from .194 +/- .092 for triglyceride to .624 +/- .093 for low-density lipoprotein-cholesterol. Cultural heritability ranges from .070 +/- .030 for total cholesterol to .149 +/- .034 for triglyceride.     

Comparison of S-phase fractions measured by flow cytometry and autoradiography in human transplant tumors

The 3H-thymidine labeling index (TLI) and the percentage of cells in the S-phase have been determined by autoradiography and by flow cytometry, (FCM), respectively, in six malignant tumors of human origin transplanted on athymic nude mice. The Dean and Jett model and the graphical model were used to determine the percent of S-phase cells by FCM. Cell cycle analysis was performed using 1) no correction for background; 2) an algebraic function for background correction; and 3) an exponential function for background subtraction. Each of these three data sets was evaluated using both the Dean and Jett model and a graphical model for the evaluation of DNA histograms. The S-phase fractions (SPF) were compared to the corresponding labeling index results. SPF without background correction were 1.54 times higher than the TLI. SPF, after correction using the algebraic model, were 1.29-fold higher than the TLI, whereas SPF obtained after background subtraction according to the exponential model were only 1.05-fold higher than the TLI. Student's t-test revealed significant differences between the mean TLI values (16.25 +/- 9.06) and the mean SPF obtained by FCM without background correction (mean 25.0 +/- 9.36, P less than 0.01), but not between the mean TLI values and the mean SPF percentages after algebraic (mean 21.0 +/- 10.29) and exponential background correction (mean 17.11 +/- 11.59), P greater than 0.05 each. There was no difference between the results obtained using the Dean and Jett model and those obtained using the graphic evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Longitudinal changes in the kinetic response to heavy-intensity exercise in children.

The purpose of this study was to investigate longitudinal changes with age in the kinetic response to cycling at heavy-intensity exercise in boys and girls. Twenty-two prepubertal children (13 male, 9 female) carried out a series of exercise tests on two test occasions with a 2-yr interval. On each test occasion, the subject completed multiple transitions from baseline to 40% of the difference between their previously determined V-slope and peak O(2) uptake (Vo(2)) for 9 min on an electronically braked cycle ergometer. Each subject's breath-by-breath responses were interpolated to 1-s intervals, time aligned, and averaged. The data after phase 1 were fit with 1) a double exponential model and 2) a single exponential model within a fitting window that was previously identified to exclude the slow component. There were no significant differences in the parameters of the primary component between each model. Subsequent analysis was carried out using model 2. The Vo(2) slow component was computed as the difference between the amplitude of the primary component and the end-exercise Vo(2) and was expressed as the percent contribution to the total change in Vo(2). Over the 2-yr period, the primary time constant (boys 16.8 +/- 5.3 and 21.7 +/- 5.3 s, girls 21.1 +/- 8.1 and 26.4 +/- 8.4 s, first and second occasion, respectively) and the relative amplitude of the slow component (boys 9.4 +/- 4.6 and 13.8 +/- 5.3%, girls 10.3 +/- 2.4 and 15.5 +/- 2.8%, first and second occasion, respectively) significantly increased with no sex differences. The data demonstrate that children do display a slow-component response to exercise and are consistent with an age-dependent change in the muscles' potential for O(2) utilization.     

Familial Resemblance in Eating Behaviors in Men and Women from the Quebec Family Study

Objective: It is commonly recognized that genetic, environmental, behavioral, and social factors are involved in the development of obesity. The family environment may play a key role in shaping children's eating behaviors. The purpose of this study was to estimate the degree of familial resemblance in eating behavioral traits (cognitive dietary restraint, disinhibition, and susceptibility to hunger). Research Methods and Procedures: Eating behavioral traits were assessed with the Three‐Factor Eating Questionnaire in 282 men and 402 women (202 families) from the Quebec Family Study. Familial resemblance for each trait (adjusted for age, sex, and BMI) was investigated using a familial correlation model. Results: The pattern of familial correlation showed significant spouse correlation for the three eating behavior phenotypes, as well as significant parent‐offspring and sibling correlations for disinhibition and susceptibility to hunger. According to the most parsimonious model, generalized heritability estimates (including genetic and shared familial environmental effects) reached 6%, 18%, and 28% for cognitive dietary restraint, disinhibition, and susceptibility to hunger, respectively. Discussion: These results suggest that there is a significant familial component to eating behavioral traits but that the additive genetic component appears to be small, with generalized heritability estimates ranging from 6% to 28%. Thus, non‐familial environmental factors and gene‐gene and gene‐environmental interactions seem to be the major determinants of the eating/behavioral traits.     

The relationship of the heart rate deflection point to the ventilatory threshold in trained cyclists

The purpose of this study was to assess the relationship of the heart rate deflection point (HRDP) to the ventilatory threshold (VT) in trained cyclists. Twenty-one endurance-trained cyclists (mean +/- SD: Vo(2)max = 67.6 +/- 4.7 ml x kg x min(-1)) completed a maximal cycle ergometer test of volitional fatigue using a ramped protocol. Ventilatory variables (Ve, Vo(2), Vco(2)) and power were measured online with averages reported every 20 seconds. Heart rate (HR) was recorded every 20 seconds using a Polar monitor. VT was calculated using the excess CO(2) elimination curve. The first derivative of a logistic growth curve fit to the HR-power data produced the HRDP. No significant differences (p > 0.01) existed between HR values at HRDP (171.7 +/- 9.6 b x min(-1)) and VT (169.8 +/- 9.9 b x min(-1)) or between Vo(2) values at HRDP (53.6 +/- 4.2 ml x kg x min(-1)) and VT (52.2 +/- 4.8 ml x kg x min(-1)). But power values at HRDP (318.7 +/- 30.7 W) were significantly different (p < 0.01) from those at VT (334.8 +/- 36.7 W). There were significant relationships between HRDP and VT for the physiological variables of HR (r = 0.92, p < 0.001), Vo(2) (r = 0.72, p < 0.001), and power (r = 0.77, p < 0.001). These findings indicate that HR and Vo(2) at HRDP are not significantly different from the values at VT in trained cyclists. HR values derived from HRDP may be used to set parameters for training intensity. Variability in the speed/power-HRDP relationship across detrained/trained states may be used to evaluate training programs.     

Shifting patterns in genetic control at the embryo-alevin boundary in brook charr

Maternal inputs to offspring early in development are initially high but the process of development suggests that ontogenetic shifts in the importance of maternal genetic variation relative to other sources should occur. We investigated additive genetic variance and covariance for direct (animal), sire, and maternal effects on embryonic length (EL), yolk sac volume (YSV), and alevin (after yolk sac resorption) length (AL) for 460 embryonic and 460 alevin brook charr (Salvelinus fontinalis) in 23 half-sib families (12 sires, 23 dams). There were no additive genetic effects of sires or individual animals on their own phenotype using sire-dam and maternal-animal models for YSV or EL (h(a)2 < 0.05). However, at the alevin stage we detected low but significant heritability for AL (h(a)2 = 0.14 +/- 0.11). Conversely, maternal genetic effects were high for both embryonic traits (h(EL)2 = 0.61 +/- 0.05; h(YSU)2 = 0.57 +/- 0.06) but faded rapidly for postresorption length (h(AL)2 = 0.18 +/- 0.04). Maternal effects in the sire-dam model corresponded highly with those in the animal-dam model. We did not detect significant genetic covariance between progeny and dams for preresorption traits or between sires and dams for any trait. However, following resorption of the yolk sac, the genetic value of dams for AL was negatively correlated with that of individual progeny (r(m,a) = -0.38 +/- 0.13), suggesting trade-offs and/or stabilizing selection between maternal and animal genetic trait value. This finding was supported by models of dam fecundity on offspring length and dam weight in phenotypic space. Heritability estimates using simple regression of embryo phenotype on adult parental phenotype produced upwardly biased estimates of genetic variance (h2 > 1.0). We propose that development through the embryo-alevin boundary may be a major point in salmonids for ontogenetic changes in the genetic architecture of embryo size from maternal genetic effects to those of the individual organism, and that maternal-offspring conflicts in resource allocation related to size may be partially indicated by negative genetic covariance.     

A biphasic model of limb venous compliance: a comparison with linear and exponential models.

Compliance is not linear within the physiological range of pressures, and linear modeling may not describe venous physiology adequately. Forearm and calf venous compliance were assessed in nine subjects. Venous compliance was modeled by using a biphasic model with high- and low-pressure linear phases separated by a breakpoint. This model was compared with a linear model and several exponential models. The biphasic, linear, and two-parameter exponential models best represented the data. The mean coefficient of determination for the biphasic model was greater than for the linear and exponential models in the calf (biphasic 0.94 +/- 0.04, exponential 0.81 +/- 0.16, P = not significant; and linear 0.54 +/- 0.05, P < 0.05) and forearm (biphasic 0.83 +/- 0.17, exponential 0.79 +/- 0.15, P = not significant; and linear 0.51 +/- 0.06, P < 0.05). The breakpoint pressure in the biphasic model was higher in the calf than the forearm, 34.4 +/- 3.9 vs. 29.1 +/- 4.5 mmHg, P < 0.05. A biphasic model can describe limb venous compliance and delineate differences in venous physiology at high and low pressures. The steep low-pressure phase of the compliance curve extends to higher pressures in the calf than in the forearm, thereby enlarging the range of pressures over which hemodynamic regulation by the calf venous circulation occurs.     

Heterogeneity between populations for multifactorial inheritance of plasma lipids

A general linear model was described for multifactorial inheritance of the two plasma lipids, total cholesterol (CH), and triglyceride (TG). Analyses of two separate studies, the Honolulu Heart Study (HHS) and the Cincinnati Lipid Research Clinic (LRC), indicated some heterogeneity. Whereas the sibling environmental effect (b) was the only source of heterogeneity between the two studies for TG, the correlation between marital environments (u) may also be considered as a source of heterogeneity for CH. Under parsimonious hypothesis, intergenerational differences in heritabilities were not found to be significant for either trait (y1 = y2 = z1 = z2 = 1). Maternal effects were significant for CH but not for TG. Correlations between marital environments (u1 and u2) were not significant for TG, and may be considered nonsignificant for CH also under parsimonious hypotheses. In any case, the genetic (h2) and cultural (c2) heritabilities cannot be considered to be heterogeneous between the two studies. Based on pooled data, parsimonious hypothesis yields: h2 = .594 +/- .041 and c2 = .035 +/- .008 for CH, and h2 = .259 +/- .034 and c2 = .108 +/- .014 for TG.     

Age-related changes in the thyroid hormone effects on malondialdehyde-modified proteins in the rat heart.

To determine the age-related changes in thyroid hormone (TH) effects on malondialdehyde (MDA)-modified proteins in cardiac tissue, rats at 4, 12, and 25 months of age were studied. Hyperthyroidism was induced with daily injection of L-triiodothyronine (15 microg/100 g) intraperitoneally for 10 days. Hypothyroidism was induced with 0. 025% methimazole in the drinking water for 4 weeks. MDA proteins were measured with immunoblots using a specific anti-MDA antiserum. MDA was measured as thiobarbituric acid reactive substance. Hypothyroidism in 4-month-old rats was associated with significant reduction in MDA proteins compared to euthyroid rats (13.4 +/- 5.9% vs. 99.8 +/- 10.4% of controls P < 0.001). Hyperthyroidism did not result in a significant change of MDA proteins. In aged rats, neither hypothyroidism nor hyperthyroidism was associated with significant changes in cardiac MDA proteins. The changes in MDA proteins did not correlate with cardiac MDA concentrations. In young rats, the MDA concentrations (nmol/mg) were significantly reduced in hypothyroidism (2.71 +/- 0.21) and were increased in hyperthyroidism (8.19 +/- 0.78) compared to euthyroid values (5.06 +/- 0.71) P < 0. 01. In aged rats, cardiac MDA content was significantly increased during both hyperthyroidism and hypothyroidism. We conclude that alterations in MDA protein content is yet another potential biochemical effect of TH in cardiac tissue. This particular effect is significantly blunted with age.     

Thiol uptake by Chinese hamster V79 cells and aerobic radioprotection as a function of the net charge on the thiol.

A series of thiols having net charge (Z) varying from -2 to +3 were studied using aerobic suspensions of Chinese hamster V79-171 cells in pH 7.4 medium at 297 K to evaluate the rate of uptake by cells and the extent of radioprotection as a function of thiol concentration in cells. For measurement of cellular levels, cells were separated from medium by centrifugation through silicone oil and tritiated water was employed to determine cell water volume. Estimated half-lives for uptake were: 2-mercaptosuccinate (Z = -2), greater than or equal to 1 h; 3-mercaptopropanoate (MPA, Z = -1), less than 2 min; 2-mercaptoethanol (2ME, Z = 0), less than 2 min; cysteamine (CyA, Z = +1), less than 2 min; N-(2-mercaptoethyl)-1,3-diaminopropane (WR-1065, Z approximately +2), approximately 40 min; N1-(2-mercaptoethyl)spermidine (WR-35980, Z approximately +3), greater than or equal to 10 h. After equilibration the cellular concentration of MPA was 60 +/- 8% of the medium level; the corresponding values for 2ME and CyA were 95 +/- 3 and 180 +/- 12%, respectively, but equilibrium was not reached for the other thiols studied. Those thiols taken up at significant rates were evaluated in terms of their ability to protect against aerobic gamma-ray-induced lethality. The results, summarized in terms of the cellular concentration of thiol (mmol dm-3) needed to achieve an aerobic radioprotection factor of 1.5, were as follows: MPA, 80 +/- 15; 2ME, 24 +/- 2; CyA, 4.7 +/- 1.3; WR-1065, 3.4 +/- 0.6. These values accorded well with those predicted from hydroxyl radical scavenging and DNA radical repair rates obtained using pBR322 DNA as a model system. This shows that hydroxyl radical scavenging and DNA radical repair are important mechanisms in the protection of cells by thiols and that the net charge on the thiol is a significant factor in its effectiveness. The results indicate that in air hydroxyl radical scavenging is the dominant mode of action by MPA, but that chemical repair of DNA radicals becomes significant for 2ME and is the dominant mechanism of protection for CyA and WR-1065.     

Evaluation of the BOD POD and leg-to-leg bioelectrical impedance analysis for estimating percent body fat in National Collegiate Athletic Association Division III collegiate wrestlers

The purpose of this study was to compare percent body fat (%BF) estimated by air displacement plethysmography (ADP) and leg-to-leg bioelectrical impedance analysis (LBIA) with hydrostatic weighing (HW) in a group (n = 25) of NCAA Division III collegiate wrestlers. Body composition was assessed during the preseason wrestling weight certification program (WCP) using the NCAA approved methods (HW, 3-site skinfold [SF], and ADP) and LBIA, which is currently an unaccepted method of assessment. A urine specific gravity less than 1.020, measured by refractometry, was required before all testing. Each subject had all of the assessments performed on the same day. LBIA measurements (Athletic mode) were determined using a Tanita body fat analyzer (model TBF-300A). Hydrostatic weighing, corrected for residual lung volume, was used as the criterion measurement. The %BF data (mean +/- SD) were LBIA (12.3 +/- 4.6), ADP (13.8 +/- 6.3), SF (14.2 +/- 5.3), and HW (14.5 +/- 6.0). %BF estimated by LBIA was significantly (p < 0.01) smaller than HW and SF. There were no significant differences in body density or %BF estimated by ADP, SF, and HW. All methods showed significant correlations (r = 0.80-0.96; p < 0.01) with HW. The standard errors of estimate (SEE) for %BF were 1.68, 1.87, and 3.60%; pure errors (PE) were 1.88, 1.94, and 4.16% (ADP, SF, and LBIA, respectively). Bland-Atman plots for %BF demonstrated no systematic bias for ADP, SF, and LBIA when compared with HW. These preliminary findings support the use of ADP and SF for estimating %BF during the NCAA WCP in Division III wrestlers. LBIA, which consistently underestimated %BF, is not supported by these data as a valid assessment method for this athletic group.     

Modifications in the TXA(2) and PGI(2) plasma levels and some other biochemical parameters during the initiation and development of non-insulin-dependent diabetes mellitus (NIDDM) syndrome in the rabbit

Having developed a non-insulin-dependent diabetes mellitus (NIDDM) syndrome model in the rabbit using Wirsung duct ligation, it appeared interesting to use it to study the relationship between glycemia and the plasma levels of TXA(2)and PGI(2), and of some other biochemical parameters such as cholesterol, triglycerides, alkaline phosphatase and transaminases. A comparative study was carried out in the sham-operated rabbits (controls, C) and those having their pancreatic duct ligatured (NIDDM, D) at 15, 30, 40, 50 and 60 days post-ligation.On the 40th days, whereas in the controls, glycemia was 1.17 +/- 0.04 g.l(-1), it reached a maximum of 4.62 +/- 0.76 g.l(-1)(25.40 mM) in the NIDDMs.No significant modification was observed either in cholesterolemia or in triglyceridemia in either group. The GOT and GPT were highly increased, from 11.50 +/- 4.00 IU. l(-1)and 27.00 +/- 1.50 IU.l(-1)(C) to 37.50 +/- 5.64 IU.l(-1)(P<0. 001) and 58.50 +/- 7.50 IU.l(-1)(D) (P<0.001) in the NIDDM group, suggesting that hyperglycemia occurred simultaneously with the degeneration of the pancreatic tissue.In parallel, in D rabbits, the plasma levels of TXB(2)and 6 keto PGF(1alpha)were augmented to 68.22 +/- 6.20 pg.ml(-1)versus 22.49 +/- 5.74 pg.ml(-1)(C) (P<0.001), and 127.11 +/- 14.39 pg.ml(-1)versus 48.65 +/- 4.51 pg.ml(-1)(C) (P<0. 001) respectively. Statistical studies showed a significant correlation (P<0.05 and <0.02) between glycemia and the biosynthesis of eicosanoids under study. Moreover, 25 mM was found to be the threshold level of glucose excess essential to increase the TXA(2)and PGI(2)biosynthesis significantly. This supports the results obtained by other authors studying the action of glucose on phospholipase activity and consequent eicosanoid production.     

Enalapril in subantihypertensive dosage attenuates kidney proliferation and functional recovery in normotensive ablation nephropathy of the rat

Most studies on the antiproliferative action of angiotensin converting enzyme inhibitors (ACEI) were performed in a rat hypertensive remnant kidney model with 5/6 kidney ablation which raised objections about the antihypertensive effect of ACEI and the influence of other antihypertensive drugs administered to remnant kidney control rats. To prevent these objections, a normotensive 4/6 remnant kidney model was elaborated and a subantihypertensive dosage of enalapril was used to evaluate its antiproliferative action. Subtotally nephrectomized rats (Nx) markedly increased the remnant kidney weight during a 4-week period and this rise was prevented by the treatment with enalapril (NxE) (Nx +297+/-35 mg vs. sham-operated +145+/-32 mg, p<0.001; NxE +154+/-35 mg vs. Nx p<0.001). While collagen concentration in the kidney cortex was not increased in sham-operated rats (Sham) in comparison with the control group (Ctrl) at the beginning of the study, the subsequent increase was significant in the Nx group and enalapril did not attenuate this increase (Sham 148+/-5 mg/100 g w.w. vs. Nx 164+/-2 mg/100 g w.w., p<0.01; NxE 161+/-4 mg/100 g w.w. vs. Sham p<0.05). The tubular protein/DNA ratio increase, which was significant in the Nx group, was inhibited by enalapril (Nx 26.2+/-10.5 vs. NxE 15.3+/-2.6, p<0.05). The protein/DNA ratio was much lower in glomeruli, with no significant changes in either the Nx or NxE groups. Serum urea concentrations were slightly higher in the Nx group than in the sham-operated group, but markedly elevated in the NxE group (Nx 10.71+/-0.76 mmol/l vs. Sham 6.10+/-0.33 mmol/l, p<0.001; NxE 28.9+/-2.6 mmol/l vs. Sham p<0.001). Creatinine concentrations in the Nx group were increased in comparison with the sham-operated group and markedly increased in the NxE group (Nx 63.7+/-3.56 micromol/l vs. Sham 37.2+/-2.84 micromol/l, p<0.001; NxE 107.0+/-5.2 micromol/l vs. Sham p<0.001). The clearance of creatinine was lower in the Nx group than in the sham-operated group and was markedly reduced in the NxE group (Nx 0.89+/-0.06 ml/min.g kidney wt. vs. Sham 1.05+/-0.16 ml/min x g kidney wt., p<0.01; NxE 0.58+/-0.029 ml/min x g kidney wt. vs. Sham, p<0.001). Enalapril improved proteinuria in comparison with the Nx group (NxE 5.6+/-0.6 mg/24 h vs. Nx 16.1+/-3.4 mg/24 h, p<0.05). Thus remnant kidney proliferation is substantial even in normotensive rats. It includes both proliferation and collagen accumulation with partial recovery of kidney weight and function, but is accompanied by enhanced proteinuria. Enalapril attenuates the proliferation and decreases proteinuria but prolongs kidney function recovery.