There has been a continuing increase in the incidence of end-stage renal disease (ESRD) in the United States, including the fraction that has been attributed to hypertension. This study was done to seek relationships between ESRD and pretreatment clinical data and between ESRD and early treated blood pressure data in a population of hypertensive veterans. We identified a total of 5730 black and 6182 nonblack male veterans as hypertensive from 1974 through 1976 in 32 Veterans Administration Hypertension Screening and Treatment Program clinics. Their mean age was 52.5 +/- 10.2 years, and their mean pretreatment blood pressure was 154.3 +/- 19.0/100.8 +/- 9.8 mm Hg. During a minimum of 13.9 years of follow-up, 5337 (44.8%) of these patients died and 245 developed ESRD. For 1055 of these subjects, pretreatment systolic blood pressure (SBP) was greater than 180 mm Hg; 901 were diabetic; 1471 had a history of urinary tract problems; and 2358 of the 9644 who were treated had an early fall in SBP of more than 20 mm Hg. We used proportional hazards modeling to fit multivariate survival models to determine the effect of the available pretreatment data and early treated blood pressure levels on ESRD. This model demonstrated the independent increased risk of ESRD associated with being black or diabetic (risk ratio, 2.2 or 1.8), having a history of urinary tract problems (risk ratio, 2.2), or having high pretreatment SBP (for SBP 165 to 180 mm Hg, risk ratio was 2.8; for SBP > 180 mm Hg, risk ratio was 7.6).(ABSTRACT TRUNCATED AT 250 WORDS)

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Receptors for epidermal growth factor (EGF) have been demonstrated in the distal tubule. To determine whether there are acute functional correlates, we studied the effect of EGF on cortical collecting tubule (CCT) transepithelial voltage and transport of sodium and bicarbonate. Rabbit CCT were perfused in vitro and EGF was added to either the bathing medium or the luminal perfusate after base-line measurements of transport. Peritubular EGF in concentrations of 0.1 to 100 ng/ml (1.7 X 10(-11) to 1.7 X 10(-8) M) decreased sodium reabsorption, measured as 22Na absorption from the lumen, by 44-59%. There was a corresponding fall in the lumen-negative transepithelial voltage. Lower doses of EGF were without effect on transepithelial voltage or sodium transport. Pretreatment of the tubules with ouabain eliminated the effect of EGF on sodium transport. In contrast to peritubular EGF, luminal EGF (100 ng/ml) did not affect sodium transport. Peritubular EGF had no effect on either bicarbonate secretion or net bicarbonate transport in the CCT and no effect on net bicarbonate reabsorption in the medullary collecting tubule. Using the pH sensitive, fluorescent dye 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, no change in principal cell intracellular pH was found after peritubular EGF. Two other growth factors, insulin and insulin-like growth factor I were without effect on sodium transport. We conclude that EGF inhibits active sodium absorption in CCT via receptors located at the basolateral membrane.

"Somatic" angiotensin I-converting enzyme (ACE) appears to be one of the evolutionary advances that made a closed circulation possible, and may have contributed to the Cambrian "explosion" of species approximately 540 million years ago. It also appears to be at the origin of a large number of common human diseases. A model is proposed in which the duplicated form of ACE ("somatic" ACE) functions as a mechanotransducer, defending downstream vessels and tissues from an increase in pressure. In the model, ACE senses shear stress (blood velocity) in regions of turbulent blood flow. An increase in shear stress strips an autoinhibitor tripeptide, FQP, from the N-terminal active site, thereby activating it. The C-terminal domain is constitutively activated by chloride. This model explains the clinical superiority of hydrophobic ACE inhibitors relative to hydrophilic ones.

The effects of parathyroid hormone on the cytoplasmic Ca2+ concentration of canine renal proximal tubule cells grown in primary culture were determined using the fluorescent Ca2+ indicator quin 2. The cultured cells exhibited responses to hormones, enzyme activities, transport functions, and morphology characteristic of the proximal convoluted tubule. Parathyroid hormone stimulated an immediate rise in cytoplasmic Ca2+, both in suspended cells and cells studied as a monolayer on Nuclepore filters. The rise in cytoplasmic Ca2+ induced by the hormone was sustained for 15-30 min, was dose dependent, and was not mimicked by cyclic AMP. Removing Ca2+ from the extracellular media markedly decreased cytoplasmic Ca2+ and abolished the effects of parathyroid hormone on cytosolic Ca2+. 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate blocked the effects of the hormone on cytosolic Ca2+, but mitochondrial uncouplers failed to inhibit the effects of the hormone to increase cytoplasmic Ca2+. These studies support a role of Ca2+ in the activation of proximal renal tubule cells by parathyroid hormone.