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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Impairments of sodium-potassium (Na-K) cotransport and lithium-sodium (Li-Na) countertransport have been reported in essential hypertension. The Vmax of Li-Na countertransport was measured in Li-loaded cells (9 mmol/l cells) by determining the external Na-stimulated Li efflux. Countertransport was measured in 29 normotensive subjects without a family history of hypertension (NT -FHH), 22 normotensive subjects with a family history of hypertension (NT +FHH) and 45 essential hypertensive patients (HT) [mean +/- s.d.: 348 +/- 138 (NT -FHH), 397 +/- 133 (NT +FHH) and 456 +/- 166 (HT)]. There was no significant elevation of Li-Na countertransport in the hypertensive group with respect to NT -FHH. The outward Na-K cotransport was measured in Na-loaded cells (Na greater than 25 mmol/l cells) by determining the frusemide-sensitive Na efflux. Na-K cotransport was found to be significantly decreased in the hypertensive patients compared to the normotensive controls [mean +/- s.d.:280 +/- 136 (HT) and 424 +/- 128 (NT -FHH)]. The present collaborative study between the two laboratories revealed that the fraction of patients with an alteration in the Vmax of cotransport or countertransport was different in the two laboratories and could not be accounted for by any methodological or experimental procedure. This study shows that different patterns of transport impairments might occur in different populations, thus suggesting a heterogeneity of cation transport alterations in hypertensives.
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PMID:The Li-Na exchange in red cells of essential hypertensive patients with low Na-K cotransport. 653 88

We have previously described elevated Lii -Nao countertransport (CT) and Na-K cotransport (CO) in red cells of Caucasian patients from Boston. In this study, we report both transport systems in black patients from Philadelphia. The maximal rate (Vmax) of CT was assayed by measuring the Nao-stimulated Li efflux from cells containing +/- 6 mmol Li/liter. The Vmax of outward cotransport was assayed by measuring the furosemide-sensitive component of Na and K efflux into Mg medium from cells containing 50 mmol/liter of both ions. The mean value of CT for 18 normotensive (NT) subjects with no family history of hypertension, (-) FHH , was 0.18 +/- 0.05 (mmol/liter cells X hour); and in 14 hypertensive (HT) patients, 0.18 +/- 0.07. The mean values of Na and K cotransport were, respectively (mmol/liter cells X hour), in 18 NT subjects with (-) FHH , 0.38 +/- 0.24 and 0.50 +/- 0.28 in 18 HT subjects, 0.25 +/- 0.17 and 0.24 +/- 0.14. We conclude that there is no difference in the Vmax for CT between the two groups of black subjects, but that the Vmax for Na-K CO was significantly reduced in the HT group. Notably, the offspring of HT patients (age 14 years, n = 17) also had a marked reduction in the Vmax of Na (0.15 +/- 0.17) K cotransport (0.19 +/- 14) in comparison with the mean value of Na (0.40 +/- 0.2) and K (0.60 +/- 0.3) cotransport measured in offspring (n = 10) of NT subjects (age 14 years).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Red cell sodium countertransport and cotransport in normotensive and hypertensive blacks. 673 56

Previous studies of glomerular permselectivity have indicated that both size selectivity and charge selectivity changes play a role in the pathogenesis of proteinuria. In this study, we measured Ficoll sieving coefficients, hemodynamic parameters, and urinary protein excretion rates in the FHH strain of fawn-hooded rats. These animals spontaneously develop systemic and glomerular hypertension, proteinuria, and focal and segmental glomerulosclerosis at a relatively young age. Three groups of FHH rats were studied: two-kidney controls (2K), untreated uninephrectomized rats (CON-NX), and uninephrectomized rats treated with the angiotensin I converting enzyme inhibitor enalapril (ENA-NX). CON-NX rats had higher glomerular transcapillary pressures (delta P) and higher urinary excretion rates of both total protein (UpV) and albumin (UaV) than did 2K rats, whereas treatment with enalapril prevented both glomerular hypertension and the increased proteinuria. Ficoll sieving coefficients were significantly higher in both groups of NX rats compared with 2K rats only for Stokes-Einstein radii (rs) > or = 46 A. Fits of sieving data to pore models showed a small increase in the number of large, nonselective pores in NX, which was not prevented by enalapril treatment. Total clearances of Ficoll with rs = 36 A (the size of albumin) in CON-NX and ENA-NX groups were unchanged compared with 2K animals. In contrast, UaV in CON-NX rats was more than six times that of 2K and ENA-NX rats. Across groups, UpV, UaV, and the ratio (UaV)/(UpV) all correlated strongly with delta P.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proteinuria and impaired glomerular permselectivity in uninephrectomized fawn-hooded rats. 781 Jun 98

Fawn-hooded (FH) rats with congenital proteinuria and systemic and glomerular hypertension are very susceptible to renal damage at a young age. In this study, the effects of unilateral nephrectomy (UNX) on the function and structure of the remaining kidney in the FHH substrain were assessed. A long-term study was performed to determine the changes in systemic blood pressure, renal function, and proteinuria during the development of chronic renal failure in UNX-FHH and two-kidney (2K) FHH rats. Renal micropuncture and morphologic studies were performed at 4 wk after surgery. The long-term study showed that, after UNX, systolic blood pressure did not differ significantly (from that of 2K-FHH rats. After UNX, there was compensatory hyperfiltration, at about 70% of the 2K level, that could be maintained for 12 wk only. The subsequent fall in GFR was preceded by severe proteinuria. The mean survival time of UNX-FHH rats was only 35 wk. Micropuncture studies showed that the high mean glomerular capillary pressure of 2K-FHH rats was further elevated after UNX. The glomerular capillary ultrafiltration coefficient did not differ significantly between UNX-FHH and 2K-FHH rats. The weight of the remaining kidney and the mean glomerular tuft volume in UNX-FHH were, on average, 36 and 31% greater than in 2K rats. The results indicate that the FHH rat is extremely vulnerable to the adverse renal effects of UNX.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathogenesis of glomerular injury in the fawn-hooded rat: effect of unilateral nephrectomy. 813 Mar 63

Fawn-hooded rats spontaneously develop focal and segmental glomerular sclerosis, systemic hypertension, and proteinuria at a young age. Micropuncture and morphological studies were performed in two inbred strains of fawn-hooded rats, FHH and FHL, with different susceptibilities to develop chronic renal failure. FHH rats have higher values for systolic blood pressure and proteinuria and more rapid development of focal and segmental glomerular sclerosis and subsequent chronic renal failure as compared with genetically closely related FHL rats. FHH and FHL strains and a Wistar control strain, WAG, were matched for age and were studied at 16 wk. FHH, FHL, and WAG-old (WAG-O) strains were matched for weight, and the last group was studied at 22 wk. WAG were also matched for weight to a young group of FHH rats (FHH-Y), and these were studied at 8 wk. In comparison with WAG and WAG-O rats, FHH and FHH-Y rats exhibited an increased in mean glomerular capillary hydraulic pressure (WAG, 52 +/- 1 mm Hg; WAG-O, 47 +/- 2 mm Hg; FHH, 60 +/- 2 mm Hg; FHH-Y, 65 +/- 1 mm Hg), whereas values in FHL animals were intermediate (56 +/- 2 mm Hg). No significant differences in glomerular volume were found among groups. Moderate focal and segmental glomerular sclerosis developed in FHH and FHH-Y rats, with values for older FHH rats being significantly greater than those for WAG, WAG-O, and FHL animals. Thus, the genetically determined sensitivity to develop proteinuria, focal and segmental glomerular sclerosis, and chronic renal failure in fawn-hooded rats correlated with early evidence of glomerular capillary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathogenesis of glomerular injury in the fawn-hooded rat: early glomerular capillary hypertension predicts glomerular sclerosis. 832 72

The spontaneously hypertensive fawn-hooded rat (FHH) develops accelerated albuminuria and focal glomerular sclerosis (FGS), leading to ESRD and shortening of lifespan. The FHH is characterized by moderate systemic hypertension, a relatively low afferent to efferent arteriolar resistance ratio, and glomerular hypertension. The FHH study presented here was designed to examine the efficacy of early-onset, late-onset, or early-temporary angiotensin I-converting enzyme inhibition (ACE-i) in ameliorating long-term hypertension and FGS, and improving survival, as well as to relate its protective efficacy to preexistent FGS and to reduction of glomerular pressure (PGC) Untreated rats developed hypertension and high PGC, and all (N = 22) except one died of ESRD within the 72-wk follow-up period. Early-onset (at 7 wk of age) ACE-i prevented development of systemic and glomerular hypertension, and it largely prevented proteinuria and FGS; all rats survived throughout the follow-up period. Rats treated with late-onset (22 wk) ACE-i were hypertensive and proteinuric at the start of ACE-i, and they showed beginning FGS. ACE-i corrected the hypertension, albuminuria, and PGC but could not fully prevent some hypertension, albuminuria, and FGS at the later stage. Early-temporary (7 to 22 wk) ACE-i adequately controlled blood pressure and development of FGS during therapy, but after withdrawal of ACE-i, systemic and glomerular hypertension developed as in untreated animals. This regimen postponed but did not control FGS development and early mortality. The results of this study indicate that: (1) early-onset ACE-i very effectively protects against development of renal damage in the FHH; (2) this protection is associated with normalization of the elevated glomerular capillary pressure; (3) ACE-i cannot completely prevent further development of previously established FGS, despite lowering glomerular capillary pressure; (4) early-temporary ACE-i has no long-term controlling effect on arterial and glomerular pressure, and it cannot control development of FGS.
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PMID:Angiotensin-converting enzyme inhibition in the prevention and treatment of chronic renal damage in the hypertensive fawn-hooded rat. 904 44

Two substrains of the fawn-hooded (FH) rat have been developed, one of which develops progressive hypertension and proteinuria, the FHH, and one which shows little increase in blood pressure and no renal damage, the FHL. Other hypertensive rodent models show primary metabolic disturbances before the development of renal damage, notably hypertriglyceridemia, which may also contribute to progression of renal disease. In this study we evaluated whether hyperlipidemia is a primary disturbance in FHH, or only occurs secondary to proteinuria. Lipid levels were determined before and after development of proteinuria, and compared to those found in age-matched FHL. We also determined whether reducing proteinuria with lisinopril would normalize lipid levels in aging FHH. At 4 weeks of age, proteinuria was very low (2-3 mg/day) in both FHH and FHL. While proteinuria increased steadily in aging FHH, reaching 350 +/- 62 mg/day at 40 weeks, much less increase was observed in FHL over the same period (32 +/- 5 mg/day at 40 weeks). Blood pressure was markedly higher in adult FHH than in FHL (158 +/- 2 vs. 129 +/- 2 mm Hg, p < 0.01). In 4-week-old FHL and FHH, plasma cholesterol levels were similar. Subsequently, cholesterol increased in FHH, reaching 3.4 +/- 0.9 mmol/l at 40 weeks, whereas cholesterol was barely affected by aging in FHL (2.1 +/- 0.2 mmol/l at 40 weeks). At 4 weeks, triglyceride levels were lowest in FHH. Subsequently, triglycerides increased in FHH, reaching 3.5 +/- 1.5 mmol/l at 40 weeks, as compared to 1.3 +/- 0.2 mmol/l in FHL. Besides a transient increase in triglyerides in lisinopril-treated FHH at 11 weeks, increments in blood pressure, proteinuria, cholesterol, triglycerides and apolipoproteins A-I, B and E aging FHH were effectively prevented by lisinopril. These data strongly suggest that there is no primary difference in lipid metabolism between FHH and FHL and that changes in plasma lipids in FHH as compared to FHL are all secondary to proteinuria.
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PMID:Hyperlipidemia is secondary to proteinuria and is completely normalized by angiotensin-converting enzyme inhibition in hypertensive fawn-hooded rats. 937 31

Genetic factors are important in determining the susceptibility to renal damage. In a backcross of the hypertensive and proteinuric fawn-hooded Erasmus University Rotterdam (FHH/EUR) rat with the normotensive, nonproteinuric August Copenhagen Irish (ACI/EUR) rat, two genes (denoted Rf-1 and Rf-2) were genetically mapped for parameters of functional and structural renal damage. The aim of the present study was to investigate the susceptibility to functional and structural renal damage in heterozygous (FHH X ACI) F1 rats compared with the parental FHH and ACI strains at similar levels of systolic BP (SBP). BP elevation was induced by chronic treatment with NG-nitro-L-arginine methyl ester (L-NAME) in either a low dose (LD, 75 to 100 mg/L) or a high dose (HD, 175 to 250 mg/L) in the drinking fluid. Survival of FHH rats and, to a lesser extent, F1 rats, was adversely affected by L-NAME treatment. All ACI rats except for one ACI-HD animal survived. In all strains, L-NAME caused a dose-dependent increase in SBP. At similar levels of SBP, the increase in functional renal damage, as indicated by the level of albuminuria, was higher in F1 compared with ACI, but lower compared with FHH. The same differences were found for the level of structural renal damage, as indicated by the incidence of glomerulosclerosis. Both the SBP and the average BP burden (SBP-Av), defined as SBP averaged over the period of follow-up, directly correlated with the level of albuminuria and incidence of glomerulosclerosis in all strains. However, the increase in the degree of renal damage per mmHg increase in SBP or SBP-Av was significantly higher in the F1 rats compared with ACI, but lower compared with FHH rats. Values for these F1 rats were closer to the ACI rats than to values for the FHH rats and increased above an SBP level of 180 mmHg. The F1 rats, being heterozygous for Rf-1 and Rf-2, as well as for other potential genes responsible for renal disease, were largely, but not completely, protected from hypertension-induced renal damage. It is concluded that complete susceptibility to hypertension-associated renal damage in rats primarily depends on the presence of predisposing genes for renal failure even after a significant increase in BP.
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PMID:Genetic differences define severity of renal damage after L-NAME-induced hypertension in rats. 951 98

The hypertensive fawn-hooded (FHH) rat develops progressive albuminuria (UalbV) and focal glomerulosclerosis (FGS). Early-onset angiotensin-converting enzyme inhibition (ACE-i) completely prevented the development of hypertension, UalbV, and FGS. ACE-i was still effective when the start of treatment was delayed, albeit less than early-onset treatment. In this study, we examined whether more advanced renal damage reduces the efficacy of ACE-i, and, if so, which factors dampen the efficacy. ACE-i was started in 36-week-old FHH rats, and follow-up consisted of regular assessment of systolic blood pressure (SBP) and UalbV. Untreated rats, matched for age, SBP, and UalbV, served as controls. In separate groups, untreated or treated with ACE-i from either week 7 or week 36, glomerular hemodynamics and FGS were determined at week 40. ACE-i normalized SBP and markedly reduced UalbV. The Initial UalbV response to ACE-i was inversely correlated with pretreatment UalbV, but despite control of SBP, UalbV rose again. Eventually, rats died of terminal renal failure. Life expectancy was significantly increased in treated rats. In both untreated and treated rats, there was a significant inverse correlation between baseline UalbV and survival time. However, the gain in survival time decreased when pretreatment UalbV was higher. Late-onset ACE-i reduced glomerular capillary pressure to the same extent as early-onset ACE-i. There was a significant linear correlation between FGS and UalbV. We conclude that in FHH rats with advanced renal damage, ACE-i slows down the progression to terminal renal failure. The outcome is an increased survival time that is inversely correlated with baseline UalbV.
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PMID:ACE inhibition delays development of terminal renal failure in the presence of severe albuminuria. 1067 17

The genetically hypertensive fawn-hooded (FHH/Eur) rat is characterized by the early presence of systolic and glomerular hypertension, progressive proteinuria (UPV), and albuminuria (UAV), and focal glomerulosclerosis, resulting in premature death from renal failure. Previous studies showed that at least five genetic loci (Rf-1 to Rf-5) were linked to the development of renal impairment. Of these five, Rf-1 appears to play a major role. To study the impact of Rf-1 in the absence of the other loci, we transferred the Rf-1 region of chromosome 1, between the markers D1Mit34 and D1Rat156, Rf-1B for short, onto the genomic background of the normotensive August x Copenhagen Irish (ACI) rat. In this congenic strain, named ACI.FHH-D1Mit34/Rat156 or ACI.FHH-Rf1B, we challenged the renal hemodynamic function of these animals by studying the effects of unilateral nephrectomy (UNX) alone, or combined with N(G)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Following UNX, the congenic strain developed significantly more UPV and UAV than the ACI progenitor. The differences were even more pronounced when UNX was combined with an L-NAME-induced rise in systolic blood pressure to about 150 mmHg, i.e., the level of hypertension present in the parental FHH strain. These findings indicate that the Rf-1B region of the FHH rat contains at least one gene affecting the susceptibility to progressive renal failure, especially in the presence of an increase in blood pressure.
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PMID:Transfer of the Rf-1 region from FHH onto the ACI background increases susceptibility to renal impairment. 1187 90


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